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Purpose: Top surgery, or masculinization of the chest, is often the first and sometimes only procedure in gender-affirming surgery for transgender- and gender-diverse persons assigned female at bir...

Cognitive skills are a strong predictor of a wide range of later life outcomes. Genetic and epigenetic associations across the genome explain some of the variation in general cognitive abilities in the general population and it is plausible that epigenetic associations might arise from prenatal environmental exposures and/or genetic variation early in life. We investigated the association between cord blood DNA methylation at birth and cognitive skills assessed in children from eight pregnancy cohorts within the Pregnancy And Childhood Epigenetics (PACE) Consortium across overall (total N = 2196), verbal (total N = 2206) and non-verbal cognitive scores (total N = 3300). The associations at single CpG sites were weak for all of the cognitive domains investigated. One region near DUSP22 on chromosome 6 was associated with non-verbal cognition in a model adjusted for maternal IQ. We conclude that there is little evidence to support the idea that variation in cord blood DNA methylation at single CpG sites is associated with cognitive skills and further studies are needed to confirm the association at DUSP22. The UK Medical Research Council and Wellcome (Grant ref: 217065/Z/19/Z) and the University of Bristol provide core support for ALSPAC. A comprehensive list of grants funding is available on the ALSPAC website (http://www.bristol.ac.uk/alspac/external/documents/grant-acknowledgements.pdf). This research was specifically funded by the BBSRC (BBI025751/1 and BB/I025263/1). GWAS data were generated by Sample Logistics and Genotyping Facilities at Wellcome Sanger Institute and LabCorp (Laboratory Corporation of America) using support from 23andMe. DCa is funded by the MRC (MC_UU_00011/1 and MC_UU_00011/5). GS is financially supported by the MRC [New Investigator Research Grant, MR/S009310/1] and the European Joint Programming Initiative “A Healthy Diet for a Healthy Life” (JPI HDHL, NutriPROGRAM project, UK MRC MR/S036520/1]. AH is supported by the South-Eastern Norway Regional Health Authority (2020022) and the Research Council of Norway (274611 and 288083). The POSEIDON work was supported by the German Research Foundation [DFG; grant FOR2107; RI908/11-2 and WI3429/3-2], the German Federal Ministry of Education and Research (BMBF) through the Integrated Network IntegraMent, under the auspices of the e:Med Programme [01ZX1314G; 01ZX1614G] through grants 01EE1406C, 01EE1409C and through ERA-NET NEURON, “SynSchiz—Linking synaptic dysfunction to disease mechanisms in schizophrenia—a multilevel investigation” [01EW1810], through ERA-NET NEURON “Impact of Early life MetaBolic and psychosocial strEss on susceptibility to mental Disorders; from converging epigenetic signatures to novel targets for therapeutic intervention” [01EW1904] and by a grant of the Dietmar-Hopp Foundation. The general design of the Generation R Study is made possible by financial support from Erasmus Medical Center, Rotterdam, Erasmus University Rotterdam, the Netherlands Organization for Health Research and Development (ZonMw) and the Ministry of Health, Welfare and Sport. The EWAS data were funded by a grant from the Netherlands Genomics Initiative (NGI)/Netherlands Organisation for Scientific Research (NWO) Netherlands Consortium for Healthy Aging (NCHA; project nr. 050-060-810), by funds from the Genetic Laboratory of the Department of Internal Medicine, Erasmus MC, and by a grant from the National Institute of Child and Human Development (R01HD068437). AN and HT are supported by a grant of the Dutch Ministry of Education, Culture, and Science and the Netherlands Organization for Scientific Research (NWO grant No. 024.001.003, Consortium on Individual Development). AN is also supported by a Canadian Institutes of Health Research team grant. The work of HT is further supported by a NWO-VICI grant (NWO-ZonMW: 016.VICI.170.200). JFF has received funding from the European Joint Programming Initiative “A Healthy Diet for a Healthy Life” (JPI HDHL, NutriPROGRAM project, ZonMw the Netherlands no. 529051022) and the European Union’s Horizon 2020 research and innovation programme (733206, LifeCycle; 633595, DynaHEALTH). The work of CAMC, JF and RM has received funding from the European Union’s Horizon 2020 Research and Innovation Programme under grant agreement No. 848158 (EarlyCause Project). Main funding of the epigenetic studies in INMA were grants from Instituto de Salud Carlos III (Red INMA G03/176, CB06/02/0041, CP18/00018), Spanish Ministry of Health (FIS-PI04/1436, FIS-PI08/1151 including FEDER funds, FIS-PI11/00610, FIS-FEDER-PI06/0867, FIS-FEDER-PI03-1615) Generalitat de Catalunya-CIRIT 1999SGR 00241, Fundació La marató de TV3 (090430), EU Commission (261357-MeDALL: Mechanisms of the Development of ALLergy), and European Research Council (268479-BREATHE: BRain dEvelopment and Air polluTion ultrafine particles in scHool childrEn). ISGlobal is a member of the CERCA Programme, Generalitat de Catalunya. SA is funded by a Juan de la Cierva—Incorporación Postdoctoral Contract awarded by Ministry of Economy, Industry and Competitiveness (IJCI-2017-34068). The Project Viva work was supported by the US National Institutes of Health grants R01 HD034568, UH3 OD023286 and R01 ES031259. The CHAMACOS project was supported by grants from the Environmental Protection Agency [R82670901 and RD83451301], the National Institute of Environmental Health Science (NIEHS) [P01 ES009605, R01ES021369, R01ES023067, R24ES028529, F31ES027751], the National Institute on Drug Abuse (NIDA) [R01DA035300], the National Institutes of Health (NIH) [UG3OD023356] and the National Institute of Mental Health (NIMH) [T32MH112510]. The content is solely the responsibility of the authors and does not necessarily represent the official views of the EPA, NIEHS, or NIH. We thank all funding sources for the EDEN study (not allocated for the present study but for the cohort): Foundation for medical research (FRM), National Agency for Research (ANR), National Institute for Research in Public health (IRESP: TGIR cohorte santé 2008 program), French Ministry of Health (DGS), French Ministry of Research, INSERM Bone and Joint Diseases National Research (PRO-A) and Human Nutrition National Research Programs, Paris–Sud University, Nestlé, French National Institute for Population Health Surveillance (InVS), French National Institute for Health Education (INPES), the European Union FP7 programs (FP7/2007-2013, HELIX, ESCAPE, ENRIECO, Medall projects), Diabetes National Research Program (in collaboration with the French Association of Diabetic Patients (AFD), French Agency for Environmental Health Safety (now ANSES), Mutuelle Générale de l’Education Nationale complementary health insurance (MGEN), French national agency for food security, French speaking association for the study of diabetes and metabolism (ALFEDIAM), grant # 2012/51290-6 Sao Paulo Research Foundation (FAPESP), EU funded MeDALL project. PREDO: The PREDO Study has been funded by the Academy of Finland (JL: 311617 and 269925, KR: 1312670 ja 128789 1287891), EraNet Neuron, EVO (a special state subsidy for health science research), University of Helsinki Research Funds, the Signe and Ane Gyllenberg foundation, the Emil Aaltonen Foundation, the Finnish Medical Foundation, the Jane and Aatos Erkko Foundation, the Novo Nordisk Foundation, the Päivikki and Sakari Sohlberg Foundation, Juho Vainio foundation, Yrjö Jahnsson foundation, Jalmari and Rauha Ahokas foundation, Sigrid Juselius Foundation granted to members of the Predo study board. Methylation assays were funded by the Academy of Finland (269925). SJL is supported by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences.

OBJECTIVE To investigate prenatal changes in cardiac biometric and flow parameters in fetuses with bicuspid aortic valve (BAV) diagnosed neonatally compared with controls with normal cardiac anatomy. METHODS This analysis was conducted as part of the Copenhagen Baby Heart Study, a multicenter cohort study of 25 556 neonates that underwent second-trimester anomaly scan at 18 + 0 to 22 + 6 weeks' gestation and neonatal echocardiography within 4 weeks after birth, in Copenhagen University Hospital Herlev, Hvidovre Hospital and Rigshospitalet in greater Copenhagen, between April 2016 and October 2018. From February 2017 (Rigshospitalet) and September 2017 (Herlev and Hvidovre hospitals), the protocol for second-trimester screening of the heart was extended to include evaluation of the four-chamber view, with assessment of flow across the atrioventricular valves, sagittal view of the aortic arch and midumbilical artery and ductus venosus pulsatility indices. All images were evaluated by two investigators, and cardiac biometric and flow parameters were measured and compared between cases with BAV and controls. All cases with neonatal BAV were assessed by a specialist. Maternal characteristics and first- and second-trimester biomarkers were also compared between the two groups. RESULTS Fifty-five infants with BAV and 8316 controls with normal cardiac anatomy were identified during the study period and assessed using the extended prenatal cardiac imaging protocol. There were three times as many mothers who smoked before pregnancy in the group with BAV as in the control group (9.1% vs 2.7%; P = 0.003). All other baseline characteristics were similar between the two groups. Fetuses with BAV, compared with controls, had a significantly larger diameter of the aorta at the level of the aortic valve (3.1 mm vs 3.0 mm (mean difference, 0.12 mm (95% CI, 0.03-0.21 mm))) and the pulmonary artery at the level of the pulmonary valve (4.1 mm vs 3.9 mm (mean difference, 0.15 mm (95% CI, 0.03-0.28 mm))). Following conversion of the diameter measurements of the aorta and pulmonary artery to Z-scores and Bonferroni correction, the differences between the two groups were no longer statistically significant. Pregnancy-associated plasma protein-A (PAPP-A) multiples of the median (MoM) was significantly lower in the BAV group than in the control group (0.85 vs 1.03; P = 0.04). CONCLUSIONS Our findings suggest that fetuses with BAV may have a larger aortic diameter at the level of the aortic valve, measured in the left-ventricular-outflow-tract view, and a larger pulmonary artery diameter at the level of the pulmonary valve, measured in the three-vessel view, at 20 weeks' gestation. Moreover, we found an association of maternal smoking and low PAPP-A MoM with BAV. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Introduction: Hospital-acquired pressure injuries are one of the most important indicators of quality patient care. It is important to identify high-risk patients to guide the implementation of appropriate prevention strategies. This can be done by using an assessment tool that covers the main risk factors for pressure injuries. Aim: The purpose of the study was to describe the incidence of pressure injuries and the associated risk factors among patients assessed with the Prevent Pressure Injury (PPI) risk assessment tool developed by the Helsinki University Hospital. Method: The study was conducted by selecting six wards from medical, surgical and neurological units. The target group were the patients being treated in the study units who gave their informed consent. The research data were retrieved from electronic patient records. Results: From the target group, 332 patients were eligible to participate in the study. The pressure injury risk was found to increase with longer hospital stays and older age. Surgical patients had an increased risk of pressure injuries compared to other specialty fields. A primary diagnosis of musculoskeletal or connective tissue disease, and secondary diagnoses of hypertension and cerebral haemorrhage, were linked with an increased pressure injury risk. A total of nine pressure injuries occurred in nine patients, with an incidence of 2.5% (stages II−IV). Conclusion: The observation and recording of pressure injuries in specialised medical care remain insufficient. Longer hospital stays, older age and surgery increase pressure injury risk. Also, patients' primary and secondary diagnoses may increase the pressure injury risk. Declaration of interest: The authors have no conflicts of interest to declare.

Aim This study aimed to describe nurses' experiences of working as members of unit practice councils. Background Health care organisations worldwide want personnel to participate in decision-making. Unit practice councils promote unit-level decision-making over unit-specific issues. Despite extensive research on shared decision-making, few studies have examined the experiences of nurses serving as members of these councils. Methods A descriptive qualitative study design was used with semi-structured interviews of 16 nurses in two clinics of a Finnish university hospital. Interviews were analysed using thematic analysis. Results The analysis revealed two themes describing nurses' experiences as members of unit practice councils: (i) inchoate unit practice councils with insufficient allocated working time and (ii) partial empowerment of nurses through the organisation's evolving Magnet project. Conclusions Unit practice councils in the studied organisations are inchoate and unable to effectively advance shared decision-making or support nurses' professional autonomy. In the future, the councils require constant support from all leadership levels of the organisation. Implications for nursing management Sharing decision-making power could be a win-win situation where nurse leaders relinquishing power over certain matters gain time to immerse in wider issues. While acknowledging different organisational roles, there is room for trusting each other's professionality and respecting autonomous work.

Background: A new anterior cruciate ligament (ACL) injury after ACL reconstruction is a feared outcome. Purpose: To study the risk of new knee injuries in female soccer players 5 to 10 years after primary unilateral ACL reconstruction and to compare players who returned to soccer with (1) players who did not return and (2) knee-healthy soccer players (controls). Study Design: Cohort study; Level of evidence, 2. Methods: Demographic, soccer-specific, and surgical data were recorded at baseline for 317 female soccer players (mean ± SD age, 20.1 ± 2.7 years) 1.6 ± 0.7 years after ACL reconstruction and for 119 matched controls (mean age, 19.5 ± 2.5 years). Data on new knee injuries and soccer-playing status were collected 5 to 10 years after ACL reconstruction via a questionnaire. Results: Among players with ACL reconstruction, 222 (70%) responded at a mean 6.5 ± 1.0 years after primary ACL reconstruction. We compared 3 cohorts: (1) among 163 players with ACL reconstruction who returned to soccer, 68 (42%) sustained 44 reruptures and 29 contralateral ruptures; (2) among 59 players with ACL reconstruction who did not return to soccer, 11 (19%) sustained 9 reruptures and 2 contralateral ruptures; and (3) among 113 knee-healthy controls, 12 (11%) sustained 13 ACL injuries. Players who returned had a >2-fold higher risk of a new ACL injury than players who did not return (risk ratio, 2.24; 95% CI, 1.27-3.93; P = .005) and a 4-fold higher risk than controls (risk ratio, 3.93; 95% CI, 2.23-6.91; P Conclusion: Two-thirds of female soccer players with ACL reconstruction who returned to soccer sustained a new knee injury within 5 to 10 years; 42% had a new ACL injury. Their risk of a new knee injury and knee surgery was 2 to 5 times greater than that for players who did not return and for knee-healthy controls. New injury may have negative consequences for long-term knee health and should be a critical consideration in the decision to return to play.

Surgery is known to be a craft profession requiring individuals with specific innate aptitude for manipulative skills, and visuospatial and psychomotor abilities. The present-day selection process of surgical trainees does not include aptitude testing for the psychomotor and manual manipulative skills of candidates for required abilities. We aimed to scrutinize the significance of innate aptitudes in surgical practice and impact of training on skills by systematically reviewing their significance on the surgical task performance. A systematic review was performed in compliance with PRISMA guidelines. An initial search was carried out on PubMed/Medline for English language articles published over 20 years from January 2001 to January 2021. Search strategy and terms to be used included ‘aptitude for surgery’, ‘innate aptitude and surgical skills, ‘manipulative abilities and surgery’, and ‘psychomotor skills and surgery’. MERSQI score was applied to assess the quality of quantitatively researched citations. The results of the present searches provided a total of 1142 studies. Twenty-one studies met the inclusion criteria out of which six citations reached high quality and rejected our three null hypothesis. Consequently, the result specified that all medical students cannot reach proficiency in skills necessary for pursuing a career in surgery; moreover, playing video games and/or musical instruments does not promote skills for surgery, and finally, there may be a valid test with predictive value for novices aspiring for a surgical career. MERSQI mean score was 11.07 (SD = 0.98; range 9.25–12.75). The significant findings indicated that medical students with low innate aptitude cannot reach skills necessary for a competent career in surgery. Training does not compensate for pictorial-skill deficiency, and a skill is needed in laparoscopy. Video-gaming and musical instrument playing did not significantly promote aptitude for microsurgery. The space-relation test has predictive value for a good laparoscopic surgical virtual-reality performance. The selection process for candidates suitable for a career in surgery requests performance in a simulated surgical environment.

AIM To translate and validate the Index of Professional Nursing Governance (IPNG) 2.0 and assess the state of professional nursing governance in Finland. BACKGROUND Raising and maintaining quality of care while retaining staff are common problems in healthcare globally. Professional governance is a modern way to tackle them, but a reliable instrument is needed to measure the state of nursing governance in Finland, and elsewhere. METHODS The IPNG that was translated into Finnish by forward-backward translation, culturally adapted and pilot tested with 20 nurses. A sample of 419 nurses was utilised in a cross-sectional study to assess the state of professional governance in Finland 2018. RESULTS Principal component analysis yielded six components with good Cronbach's α values. The results clearly indicate that the IPNG version developed and evaluated in this study has suitable psychometric properties for use in Finnish healthcare settings. The validated IPNG scores indicate that nursing governance in Finland is in the professional governance range. The staff have some input in the governance of Finnish healthcare organisations. However, this perception is strongest among the nurse leaders and experts; other groups do not perceive much change yet. CONCLUSION Participants, particularly nurse leaders in Finland, had self-reported impact in decision-making. The translated IPNG has acceptable internal consistency and can be used to assess healthcare organisations' governance models in Finland and broader in Nordic countries and Europe.

Objective To explore diagnoses of postpartum haemorrhage following vaginal birth, in relation to socio-demographic and obstetrical data from women who gave birth at term, in Sweden, during the years 2005–2015. Study design A register-based cohort study was carried out, describing and comparing socio-demographic variables, obstetric variables and infant variables in 52 367 cases of diagnosed postpartum haemorrhage compared to 353 569 controls without a postpartum haemorrhage diagnosis. Postpartum hemorrhage was identified in The Swedish Medical Birth Register by ICD-10 code O72. Variables for maternal characteristics were dichotomized and used to calculate odds ratios to find possible explanatory variables for postpartum haemorrhage. Results Between 2005 and 2015 there was no statistically significant decrease in diagnoses of postpartum haemorrhage after vaginal birth at term. Primiparity was associated with the highest risk and women birthing their fifth or subsequent child were associated with the lowest risk of postpartum hemorrhage. Increased maternal age (> 35 years) and/or obesity (BMI > 30) were associated with higher odds of postpartum haemorrhage. The risk of postpartum hemorrhage was 55 % higher when vaginal birth followed induction as compared to vaginal birth after spontaneous onset. Some of the factors known to be associated with postpartum haemorrhage were poorly documented in The Swedish Medical Birth Register. Conclusions Birthing women in a Swedish contemporary setting are, despite efforts to improve care, still at risk of birth being complicated by postpartum haemorrhage. Primiparity, increasing maternal age and/or obesity are found to provoke an increased risk and the reasons for these findings need to be further investigated. However, grand multi-parity did not increase the risk for postpartum hemorrhage. Codes for diagnoses require correct documentation in the birth records: only when local statistics are sound and correctly reported can intrapartum care be improved, and the incidence of postpartum haemorrhage reduced.

Background: With a globally increasing population of otherwise healthy people above 70 years, more knowledge on treatment and prognosis of breast cancer patients in this group is needed. In Denmark, the Danish Breast Cancer Group describes national treatment guidelines for diagnostic work-up and surgical and oncological treatment of all patients with primary invasive breast cancer with no upper age limit. Still, many patients ≥70 years, regardless of comorbidity, do not adhere to treatment guidelines, often receiving less imaging and less treatment than recommended. The aims of the present study were to examine, among patients ≥70 years with primary invasive breast cancer, whether endocrine treatment only, resulted in an inferior breast cancer related survival compared to standard surgical and oncological treatment, to examine whether patients treated with breast conserving surgery (BCS) with no preoperative imaging had a higher risk of local recurrence than patients receiving preoperative imaging, and finally to examine whether clinically node negative patients had a higher risk of regional recurrence if they did not receive axillary staging. Methods: All women, ≥70 years, diagnosed with primary invasive breast cancer and treated at the Department of Breast Surgery at Herlev Hospital, Denmark, from 2000-2007 were included. Patients were prospectively registered in a hospital-based database. Differences in standardized mortality ratios (SMR) between patients treated by surgery, endocrine therapy only, or endocrine therapy followed by surgery were estimated by Poisson regression and evaluated by rate ratios. Differences in local recurrence between patients with and without preoperative imaging before BCS, and in regional recurrence between surgically treated patients with and without a sentinel lymph node biopsy, with axillary clearance in case of a positive sentinel node, excluding clinically node positive patients directly treated with an axillary clearance, were estimated by Cause Specific Hazards Models and evaluated by cause specific hazard ratios (HR). Adjustments were made for age, comorbidity, adjuvant radiotherapy, tumor size, time since diagnosis, and time period. Results: In total 1,142 patients were included in the study. The median age was 77 years. For overall mortality, median follow-up was 7.80 years, with 795 (69.6%) dying during follow-up, and for recurrence 6.25 years. 52 were registered with local recurrence and 39 with regional recurrence. Patients who received only endocrine therapy had a significantly higher SMR than patients treated with primary surgery (adj. RR=2.57; 95% CI: 2.01-3.30), while patients who received endocrine therapy followed by later surgery did not (RR=1.23; 95% CI: 0.91-1.66). 253 out of 580 patients with BCS (43.6%) did not have preoperative imaging. Patients without imaging did not have a higher risk of local recurrence compared to patients with preoperative imaging (adj. HR=1.14; 95% CI: 0.36-3.67). 13 out of 197 surgically treated patients without axillary surgery (6,8%) had regional recurrence, while only 7 out of 428 patients (1.6%) with axillary staging by sentinel node biopsy had regional recurrence. This difference was significant (adj. HR 4.68 95% CI=1.53-14.37). Conclusions: In the present study we have shown that women ≥70 years, diagnosed with primary invasive breast cancer, have a higher mortality if they are not surgically treated, and they have a higher risk of regional recurrence if they are not offered axillary staging. The study emphasizes that unless elderly patients have comorbidity contraindicating surgery, they should be treated according to guidelines. Citation Format: Mathias Kvist Mejdahl, Mette Haulund Christensen, Birgitte Paaschburg Nielsen, Tove HolstFiltenborg Tvedskov. Elderly breast cancer patients benefit from surgery according to guidelines [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS1-07.

BACKGROUNDGenetic testing for breast cancer susceptibility is widely used, but for many genes,evidence of an association with breast cancer is weak, underlying risk estimatesare imprecise, and reliable subtype-specific risk estimates are lacking.METHODSWe used a panel of 34 putative susceptibility genes to perform sequencing onsamples from 60,466 women with breast cancer and 53,461 controls. In separateanalyses for protein-truncating variants and rare missense variants in these genes,we estimated odds ratios for breast cancer overall and tumor subtypes. We evaluatedmissense-variant associations according to domain and classification of pathogenicity.RESULTSProtein-truncating variants in 5 genes (ATM, BRCA1, BRCA2, CHEK2, and PALB2)were associated with a risk of breast cancer overall with a P value of less than0.0001. Protein-truncating variants in 4 other genes (BARD1, RAD51C, RAD51D,and TP53) were associated with a risk of breast cancer overall with a P value ofless than 0.05 and a Bayesian false-discovery probability of less than 0.05. Forprotein-truncating variants in 19 of the remaining 25 genes, the upper limit ofthe 95% confidence interval of the odds ratio for breast cancer overall was lessthan 2.0. For protein-truncating variants in ATM and CHEK2, odds ratios werehigher for estrogen receptor (ER)–positive disease than for ER-negative disease;for protein-truncating variants in BARD1, BRCA1, BRCA2, PALB2, RAD51C, andRAD51D, odds ratios were higher for ER-negative disease than for ER-positivedisease. Rare missense variants (in aggregate) in ATM, CHEK2, and TP53 wereassociated with a risk of breast cancer overall with a P value of less than 0.001.For BRCA1, BRCA2, and TP53, missense variants (in aggregate) that would be classified as pathogenic according to standard criteria were associated with a riskof breast cancer overall, with the risk being similar to that of protein-truncatingvariants.CONCLUSIONSThe results of this study define the genes that are most clinically useful for inclusion on panels for the prediction of breast cancer risk, as well as provide estimatesof the risks associated with protein-truncating variants, to guide genetic counseling. (Funded by European Union Horizon 2020 programs and others.)

While technical and profession-specific competencies are paramount in the delivery of healthcare services, the cross-cutting core competencies of healthcare professionals play an important role in healthcare transformation, innovation, and the integration of roles. This systematic review describes the characteristics and psychometric properties of existing instruments for assessing healthcare professionals' core competencies in clinical settings. It was guided by the JBI methodology and used the COSMIN checklist (Mokkink et al., User manual, 2018, 78, 1) to evaluate the methodological quality of the included studies. A database search (CINAHL, Scopus, and PubMed) and additional manual search were undertaken for peer-reviewed papers with abstracts, published in English between 2008 and 2019. The search identified nine studies that were included in the synthesis demonstrating core competencies in professionalism, ethical and legal issues, research and evidence-based practice, personal and professional development, teamwork and collaboration, leadership and management, and patient-centered care. Few instruments addressed competencies in quality improvement, safety, communication, or health information technology. The findings demonstrate the reviewed tools' validity and reliability and pave the way for a comprehensive evaluation and assessment of core competencies into clinical practice.

Objective: The study aimed to investigate the association between placental growth factor (PlGF) and adverse obstetric outcomes in a mixed-risk cohort of pregnant women screened for preeclampsia (PE) in the first trimester. Methods: We included women with singleton pregnancies screened for PE between April 2014 and September 2016. Outcome data were retrieved from the New South Wales Perinatal Data Collection (NSW PDC) by linkage to the prenatal cohort. Adverse outcomes were defined as spontaneous preterm birth (sPTB) before 37-week gestation, birth weight (BW) below the 3rd centile, PE, gestational hypertension (GH), stillbirth, and neonatal death. Results: The cohort consisted of 11,758 women. PlGF multiple of the median (MoM) was significantly associated with maternal sociodemographic characteristics (particularly smoking status and parity) and all biomarkers used in the PE first trimester screening model (notably pregnancy-associated plasma protein A MoM and uterine artery pulsatility index [PI] MoM). Low levels of PlGF (Conclusions: Low PlGF MoM levels are independently associated with PE and a range of other adverse pregnancy outcomes. Inclusion of PlGF should be considered in future models screening for adverse pregnancy outcomes in the first trimester.

AIMS To describe the quality of care for older cancer patients in acute care settings as perceived by the responsible nursing staff. METHODS A cross-sectional study design was used. Data were collected using a questionnaire completed by 90 nursing staff at a university hospital and a city hospital. Quality of care was measured using the Revised Humane Caring Scale. Descriptive statistics, reliability analysis, nonparametric tests and linear regression analysis were used to analyse the data. FINDINGS Generally, the nursing staff perceived the quality of care as good; however, university hospital nursing staff perceived the quality of care to be better than city hospital nursing staff. Compared with other age groups, nursing staff in the 30- to 40-year age group more frequently indicated that patients' information and participation need improvement. Moreover, supplemental education in cancer care was found to have no significant impact on the quality of care. Altogether, nursing staff disagreed the most about their perceptions of staffing, sufficient time and an unhurried atmosphere. CONCLUSION Nursing staff should focus more on patients' personal needs, particularly with regard to patients' provision of information and participation in care. Younger nurses need more support and mentoring about complex care from their experienced colleagues when performing their work. Leaders should guarantee availability of the adequate number of competent staff in hospital wards.

Objectives: To explore the impact of anti-hypertensive treatment of pregnancy-induced hypertension on foetal growth and hemodynamics in women with pre-existing diabetes. Methods: A prospective cohort study of 247 consecutive pregnant women with pre-existing diabetes (152 type 1 diabetes; 95 type 2 diabetes), where tight anti-hypertensive treatment was initiated and intensified (mainly with methyldopa) when office blood pressure (BP) ≥135/85 mmHg and home BP ≥130/80 mmHg. Foetal growth was assessed by ultrasound at 27, 33 and 36 weeks and foetal hemodynamics were assessed by ultrasound Doppler before and 1–2 weeks after initiation of anti-hypertensive treatment. Results: In 215 initially normotensive women, anti-hypertensive treatment for pregnancy-induced hypertensive disorders was initiated in 42 (20%), whilst 173 were left untreated. Chronic hypertension was present in 32 (13%). Anti-hypertensive treatment for pregnancy-induced hypertensive disorders was not associated with foetal growth deviation (linear mixed model, p = 0.681). At 27 weeks, mainly before initiation of anti-hypertensive treatment, the prevalence of small foetuses with an estimated foetal weight

Background and objective The European consortium project TRANSPOSE (TRANSfusion and transplantation: PrOtection and SElection of donors) aimed to assess and evaluate the risks to donors of Substances of Human Origin (SoHO), and to identify gaps between current donor vigilance systems and perceived risks. Materials and methods National and local data from participating organizations on serious and non-serious adverse reactions in donors were collected from 2014 to 2017. Following this, a survey was performed among participants to identify risks not included in the data sets. Finally, participants rated the risks according to severity, level of evidence and prevalence. Results Significant discrepancies between anticipated donor risks and the collected data were found. Furthermore, many participants reported that national data on adverse reactions in donors of stem cells, gametes, embryos and tissues were not routinely collected and/or available. Conclusions These findings indicate that there is a need to further develop and standardize donor vigilance in Europe and to include long-term risks to donors, which are currently underreported, ensuring donor health and securing the future supply of SoHO.

OBJECTIVE: ITPR3, encoding inositol 1,4,5-trisphosphate receptor type 3, was previously reported as a potential candidate disease gene for Charcot-Marie-Tooth neuropathy. Here, we present genetic and functional evidence that ITPR3 is a Charcot-Marie-Tooth disease gene. METHODS: Whole-exome sequencing of four affected individuals in an autosomal dominant family and one individual who was the only affected individual in his family was used to identify disease-causing variants. Skin fibroblasts from two individuals of the autosomal dominant family were analyzed functionally by western blotting, quantitative reverse transcription PCR, and Ca2+ imaging. RESULTS: Affected individuals in the autosomal dominant family had onset of symmetrical neuropathy with demyelinating and secondary axonal features at around age 30, showing signs of gradual progression with severe distal leg weakness and hand involvement in the proband at age 64. Exome sequencing identified a heterozygous ITPR3 p.Val615Met variant segregating with the disease. The individual who was the only affected in his family had disease onset at age 4 with demyelinating neuropathy. His condition was progressive, leading to severe muscle atrophy below knees and atrophy of proximal leg and hand muscles by age 16. Trio exome sequencing identified a de novo ITPR3 variant p.Arg2524Cys. Altered Ca2+ -transients in p.Val615Met patient fibroblasts suggested that the variant has a dominant-negative effect on inositol 1,4,5-trisphosphate receptor type 3 function. INTERPRETATION: Together with two previously identified variants, our report adds further evidence that ITPR3 is a disease-causing gene for CMT and indicates altered Ca2+ homeostasis in disease pathogenesis. ispartof: ANNALS OF CLINICAL AND TRANSLATIONAL NEUROLOGY vol:7 issue:10 pages:1962-1972 ispartof: location:United States status: published

Aims and objectives To describe the nurse-patient ratio in the paediatric emergency department and whether it is related to emergency care process measurements: length of stay and the number of patients who leave before treatment is completed. Background Despite abundant data on nurse staffing, little is known about its relationship with process variables in paediatric emergency departments. Design This was a cross-sectional study. Administrative data regarding 21,956 patients and nurse staffing (N = 49) were collected from a university hospital's paediatric emergency department between 1 January-30 June 2019. Summary statistics were calculated, differences in the variables were assessed by Kruskal-Wallis and chi-square tests, and relations between them were explored by linear regression analysis. This study is reported in accordance with the STROBE guidelines. Results Nurse-patient ratios varied between shifts and were highest at night (mean 0.75; range 0.3-5.3) and the lowest in the evenings (mean 0.17; range 0.1-0.8). Increases in numbers of nurses in the paediatric emergency department reduced the length of stay by 2% per additional nurse on average, and nurse-patient ratios were negatively related to frequencies of patients leaving before treatment completion. Conclusion The results indicate that nurse-patient ratios affect paediatric patient care processes. Staffing levels are negatively related to emergency department length of stay and influence factors that could reduce numbers of patients who leave before treatment completion. Relevance to clinical practice Because the nurse-patient ratio affects the care process, it should be used together with other process measurements when assessing care quality in paediatric emergency departments.

Positive staining of testicular germ cells for PLAP and c-Kit beyond infancy may be associated with the presence of GCNIS (Germ Cell Neoplasia In Situ). We recently reported our findings of positive staining of normal, infantile germ cells for PLAP, and c-Kit up to 2 years of age, contrary to previous studies. The present study aims to elucidate whether otherwise normal testes of boys undergoing puberty express PLAP, c-Kit, Oct3/4, or D2-40. Biopsies were taken from 31 boys (11.5–16.5 years of age, mean and median of 13.5 years), who underwent surgery either for torsion of the testis (15) or a history suspicious of intermittent torsion of the testis (16). 21 were biopsied on both sides, making a total of 52 biopsies. Four testes were necrotic. The biopsies were fixed in Stieve’s medium, cut into 2 μm sections, and mounted on coated slides. One slide was processed for H–E, and the others incubated with primary antibody for PLAP, c-Kit, D2-40, and Oct3/4. 87% of the boys stained positive for both PLAP and c-Kit. None were positive for either D2-40 or Oct3/4. None had any histological features characteristic of GCNIS. Only two boys showed no signs of having initiated spermatogenesis. Those positive for PLAP were likewise for c-Kit, and vice versa, except 2; one boy, 13 years, was positive for PLAP, but negative for c-KIT, another, 16 years, was negative for PLAP and positive for c-Kit. Three boys stained positive for PLAP and c-Kit on the right side, and negative on the left. One boy was negative for c-Kit on the right side, positive on the left, and positive for PLAP bilaterally. Positive staining of testicular germ cells for PLAP and c-Kit seems to be a normal finding in boys not having completed puberty. Rather than indicating pre-malignant transformation, the positivity is indicative of an ongoing maturational process of the germ cells.

Background Sustaining injury is a common consequence of playing sport. At least one in every three recreational athletes with anterior cruciate ligament (ACL) reconstruction do not return to their preinjury sport following treatment. Psychological factors including confidence and fear of new injury exert large effects on returning to sport. The primary aim of this trial is to test whether a custom smartphone application delivering cognitive-behavioural therapy is effective for improving the number of people who return to their preinjury sport and level following ACL reconstruction. Methods Participants scheduled for primary ACL reconstruction are recruited prior to surgery from one of six trial sites in Sweden. We aim to recruit 222 participants (111 in each group) for the BANG trial. Participants are randomly allocated to receive either usual rehabilitation care alone or usual rehabilitation care plus the Back in the Game smartphone application intervention. Back in the Game is a 24-week Internet-delivered programme, based on cognitive-behavioural therapy. The primary outcome is return to the preinjury sport and level at 12 months follow-up. The secondary outcomes assess physical activity participation, new knee injuries, psychological factors, quality of life and physical function. Physical activity participation and new injuries are self-reported every two weeks for 12 months, then every 4 weeks to 24 months follow-up. Psychological readiness to return to sport, knee self-efficacy, motivation to participate in leisure time physical activity, knee-related quality of life, and self-reported knee function are also assessed at 3, 6, 9, 12 and 24 months after surgery. A clinical assessment of strength, knee range of motion, effusion and hopping performance is completed by a blinded assessor at 12 months to assess physical function. Discussion This protocol outlines how we plan to assess the efficacy of a custom smartphone application, delivering cognitive-behavioural therapy to address fear, confidence and recovery expectations, for improving return to sport following serious sports-related musculoskeletal injury. The BANG trial employs a pragmatic design to best reflect the reality of, and inform, clinical practice. Trial registration ClinicalTrials.gov, NCT03959215. Registered 22 May 2019.

The aim of the present study was to describe histopathologic characteristics of synchronous bilateral breast cancer (SBBC), and by comparing SBBC to unilateral breast cancer (UBC), identify possible etiological mechanisms of SBBC. Patients with primary SBBC (diagnosed within 4 months) and UBC diagnosed in Denmark between 1999 and 2015 were included. Detailed data on histopathology were retrieved from the Danish Breast Cancer Group database and the Danish Pathology Register. Associations between bilateral disease and the different histopathologic characteristics were evaluated by odds ratios and estimated by multinomial regression models. 1214 patients with SBBC and 59,221 with UBC were included. Patients with SBBC more often had invasive lobular carcinomas (OR 1.29; 95% CI 1.13–1.47), a clinically distinct subtype of breast cancer, than UBC patients. Further, they were older than UBC patients, more often had multifocal cancer (OR 1.13; 95% CI 1.01–1.26), and a less aggressive subtype than UBC patients. Invasive lobular carcinoma was associated with having multiple tumors in breast tissue—both in the form of bilateral disease and multifocal disease, and this association was independent of laterality. No similar pattern was observed for other tumor characteristics. We identified two etiological mechanisms that could explain some of the occurrence of SBBC. The high proportion of less aggressive carcinomas and higher age of SBBC compared to UBC patients suggests that many are diagnosed at a subclinical stage as slow-growing tumors have a higher probability of simultaneous diagnosis. The high proportion of invasive lobular carcinoma observed in bilateral and multifocal disease, being independent of laterality, suggests that these patients have an increased propensity to malignant tumor formation in breast tissue.

AIM To test the hypothesis that in the daily routine of a specialist clinic in endodontics that irrigation during root canal preparation with 3.0% NaOCl will result in fewer postoperative samples with cultivable bacteria than irrigation with 0.5% buffered NaOCl but, at the same time, will not result in a higher frequency of postoperative pain nor swelling. METHODOLOGY Two hundred ninety-eight patients were enrolled in the study and were randomly assigned into two groups - 0.5% NaOCl and 3% NaOCl. All endodontic diagnoses were included. Root canal treatment was performed, and bacterial sampling was carried out prior to root filling. The patients were requested to complete a form regarding pain and swelling seven days postoperatively. Fisher's exact test, Mann-Whitney U-test, Mantel-Haenszel chi-squared and the chi-squared test with a significance level of P

Background When deciding medical treatment, patients' perspectives are important. There is limited knowledge about patients' views when choosing non-operative treatment or anterior cruciate ligament (ACL) reconstruction (ACLR) after ACL injury. Purpose To describe reasons that influenced patients' decisions for non-operative treatment or ACLR after ACL injury. Study design Cross-sectional study. Methods This study recruited a total of 223 patients (50% men), aged 28 ± 8 years who had sustained ACL injury, either unilateral or bilateral. Subjects were, at different time points after injury, asked to fill out a questionnaire about their choice of treatment, where an ACLR treatment decision was made, some responded before and some after the ACLR treatment. A rating of the strength of 10 predetermined reasons in their choice of treatment graded as 0 (no reason) to 3 (very strong reason), was done. Results Patients with unilateral ACL injury treated with ACLR (110 patients) rated "inability to perform physical activity at the same level as before the injury due to impaired knee function" (96%), "fear of increased symptoms during activity" (87%) and "giving way episodes" (83%) as strong or very strong reasons in their treatment decision. Patients with bilateral ACL injury treated with ACLR (109 knees) rated similar reasons as patients with unilateral ACLR and also "low confidence in the ability to perform at the preinjury activity level without ACLR" (80%) as strong or very strong reasons. Patients with unilateral ACL injury treated non-operatively (46 patients) rated "advice from clinician" (69%) as a strong or very strong reason. Patients with bilateral ACL injury treated non-operatively (25 knees) rated "absence of giving way episodes" (62%), and "no feeling of instability" (62%) as strong or very strong reasons. Conclusion Inability to perform physical activity, fear of increased symptoms, and giving way episodes were reasons that patients with ACL injury considered when making decisions about ACLR. When choosing non-operative treatment, patients considered the absence of instability or giving way symptoms, being able to perform physical activity, and advice from clinicians. Level of evidence 4.

Background The tuck jump assessment was developed to identify players at risk for anterior cruciate ligament (ACL) injuries or gauge a player's progress through rehabilitation after ACL reconstruction. A tuck jump score of ≥ 6 out of 10 has been labeled poor and thought to identify players with high risk landing patterns. Purpose The purpose of this exploratory study was to examine if there was a relationship between tuck jump score, particularly tuck jump scores ≥ 6, hopping performance, and patient-reported outcome measures in female soccer players with ACL reconstruction (ACLR) and knee-healthy controls. Study Design Secondary analysis of prospective cohort study. Methods Female soccer players (117 after ACLR, 117 knee-healthy) performed the single hop for distance, tuck jump assessment, and drop vertical jump (DVJ). All players were categorized based on as having a total tuck jump score ≥ 6 or

PURPOSE To estimate age-specific relative and absolute cancer risks of breast cancer and to estimate risks of ovarian, pancreatic, male breast, prostate, and colorectal cancers associated with germline PALB2 pathogenic variants (PVs) because these risks have not been extensively characterized. METHODS We analyzed data from 524 families with PALB2 PVs from 21 countries. Complex segregation analysis was used to estimate relative risks (RRs; relative to country-specific population incidences) and absolute risks of cancers. The models allowed for residual familial aggregation of breast and ovarian cancer and were adjusted for the family-specific ascertainment schemes. RESULTS We found associations between PALB2 PVs and risk of female breast cancer (RR, 7.18; 95% CI, 5.82 to 8.85; P = 6.5 × 10−76), ovarian cancer (RR, 2.91; 95% CI, 1.40 to 6.04; P = 4.1 × 10−3), pancreatic cancer (RR, 2.37; 95% CI, 1.24 to 4.50; P = 8.7 × 10−3), and male breast cancer (RR, 7.34; 95% CI, 1.28 to 42.18; P = 2.6 × 10−2). There was no evidence for increased risks of prostate or colorectal cancer. The breast cancer RRs declined with age ( P for trend = 2.0 × 10−3). After adjusting for family ascertainment, breast cancer risk estimates on the basis of multiple case families were similar to the estimates from families ascertained through population-based studies ( P for difference = .41). On the basis of the combined data, the estimated risks to age 80 years were 53% (95% CI, 44% to 63%) for female breast cancer, 5% (95% CI, 2% to 10%) for ovarian cancer, 2%-3% (95% CI females, 1% to 4%; 95% CI males, 2% to 5%) for pancreatic cancer, and 1% (95% CI, 0.2% to 5%) for male breast cancer. CONCLUSION These results confirm PALB2 as a major breast cancer susceptibility gene and establish substantial associations between germline PALB2 PVs and ovarian, pancreatic, and male breast cancers. These findings will facilitate incorporation of PALB2 into risk prediction models and optimize the clinical cancer risk management of PALB2 PV carriers.

Background Individuals with cerebral palsy (CP) are less physically active, spend more time sedentary and have lower cardiorespiratory endurance as compared to typically developed individuals. RaceRunning enables high-intensity exercise in individuals with CP with limited or no walking ability, using a three-wheeled running bike with a saddle and a chest plate for support, but no pedals. Training adaptations using this type of exercise are unknown. Methods Fifteen adolescents/young adults (mean age 16, range 9–29, 7 females/8 males) with CP completed 12 weeks, two sessions/week, of RaceRunning training. Measurements of cardiorespiratory endurance (6-min RaceRunning test (6-MRT), average and maximum heart rate, rate of perceived exertion using the Borg scale (Borg-RPE)), skeletal muscle thickness (ultrasound) of the thigh (vastus lateralis and intermedius muscles) and lower leg (medial gastrocnemius muscle) and passive range of motion (pROM) of hip, knee and ankle were collected before and after the training period. Results Cardiorespiratory endurance increased on average 34% (6-MRT distance; pre 576 ± 320 m vs. post 723 ± 368 m, p p p p Conclusions These results support the efficacy of RaceRunning as a powerful and effective training modality in individuals with CP, promoting both cardiorespiratory and peripheral adaptations.

Fear of childbirth (FOC) can lead to maternal distress during and after pregnancy. The aim of this randomized controlled trial (RCT) was to examine whether art therapy as an adjunct to midwife-led ...

Introduction: Supraventricular tachycardia is the most common fetal tachyarrhythmia and if persistent often associated with fetal hydrops which can cause intrauterine and neonatal death. Case Presentation: We present a case of early second trimester supraventricular tachycardia in a hydropic fetus, initially refractory to transplacental treatment. Conclusion: The supraventricular tachycardia was successfully treated when supplemented with intraperitoneal flecainide in the fetus.

This practical, extensively illustrated handbook covers the procedures that are undertaken in andrology and ART laboratories to analyse and assess male-factor infertility, and to prepare spermatozoa for use in assisted conception therapy. The content is presented as brief, authoritative overviews of the relevant biological background for each area, plus detailed, step-by-step descriptions of the relevant analytical procedures. Each technical section includes quality control considerations and the optimum presentation of results. In addition to the comprehensive 'basic' semen analysis, incorporating careful analysis of sperm morphology, the handbook provides established techniques for the use of computer-aided sperm analysis and sperm functional assessment. The interpretation of laboratory results in the clinical context is highlighted throughout, and safe laboratory practice is emphasized. Fully revised, incorporating the new ISO TS 23162 on basic human semen analysis throughout, this is an invaluable resource to all scientists and technicians who perform diagnostic testing for male-factor infertility.

Purpose: Germline genetic testing for BRCA1 and BRCA2 variants has been a part of clinical practice for >2 decades. However, no studies have compared the cancer risks associated with missense pathogenic variants (PVs) with those associated with protein truncating (PTC) variants.Methods: We collected 582 informative pedigrees segregating 1 of 28 missense PVs in BRCA1 and 153 pedigrees segregating 1 of 12 missense PVs in BRCA2. We analyzed 324 pedigrees with PTC variants in BRCA1 and 214 pedigrees with PTC variants in BRCA2. Cancer risks were estimated using modified segregation analysis.Results: Estimated breast cancer risks were markedly lower for women aged >50 years carrying BRCA1 missense PVs than for the women carrying BRCA1 PTC variants (hazard ratio [HR] = 3.9 [2.4-6.2] for PVs vs 12.8 [5.7-28.7] for PTC variants; P =.01), particularly for missense PVs in the BRCA1 C-terminal domain (HR = 2.8 [1.4-5.6]; P =.005). In case of BRCA2, for women aged >50 years, the HR was 3.9 (2.0-7.2) for those heterozygous for missense PVs compared with 7.0 (3.3-14.7) for those harboring PTC variants. BRCA1 p.[Cys64Arg] and BRCA2 p.[Trp2626Cys] were associated with particularly low risks of breast cancer compared with other PVs.Conclusion: These results have important implications for the counseling of at-risk women who harbor missense PVs in the BRCA1/2 genes. (C) 2021 American College of Medical Genetics and Genomics. Published by Elsevier Inc. All rights reserved.

Breast and prostate cancer risks; Pathogenic variant Riscos de càncer de mama i pròstata; Variants patogèniques Riesgos de cáncer de mama y próstata; Variantes patogénicas Background Recent population-based female breast cancer and prostate cancer polygenic risk scores (PRS) have been developed. We assessed the associations of these PRS with breast and prostate cancer risks for male BRCA1 and BRCA2 pathogenic variant carriers. Methods 483 BRCA1 and 1318 BRCA2 European ancestry male carriers were available from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). A 147-single nucleotide polymorphism (SNP) prostate cancer PRS (PRSPC) and a 313-SNP breast cancer PRS were evaluated. There were 3 versions of the breast cancer PRS, optimized to predict overall (PRSBC), estrogen receptor (ER)–negative (PRSER-), or ER-positive (PRSER+) breast cancer risk. Results PRSER+ yielded the strongest association with breast cancer risk. The odds ratios (ORs) per PRSER+ standard deviation estimates were 1.40 (95% confidence interval [CI] =1.07 to 1.83) for BRCA1 and 1.33 (95% CI = 1.16 to 1.52) for BRCA2 carriers. PRSPC was associated with prostate cancer risk for BRCA1 (OR = 1.73, 95% CI = 1.28 to 2.33) and BRCA2 (OR = 1.60, 95% CI = 1.34 to 1.91) carriers. The estimated breast cancer odds ratios were larger after adjusting for female relative breast cancer family history. By age 85 years, for BRCA2 carriers, the breast cancer risk varied from 7.7% to 18.4% and prostate cancer risk from 34.1% to 87.6% between the 5th and 95th percentiles of the PRS distributions. Conclusions Population-based prostate and female breast cancer PRS are associated with a wide range of absolute breast and prostate cancer risks for male BRCA1 and BRCA2 carriers. These findings warrant further investigation aimed at providing personalized cancer risks for male carriers and informing clinical management. The CIMBA data management and data analysis were supported by Cancer Research UK grants C12292/A20861 and PPRPGM-Nov20\100002. The research leading to these results has received funding from the Italian Association for Cancer Research (AIRC) under IG 2018 - ID. 21389 and the Italian League for the Fight Against Cancer (LILT) under IG 2019 projects, P.I. Ottini Laura and Italian Ministry of Education, Universities and Research-Dipartimenti di Eccellenza-L. 232/2016. CIMBA: GCT is a National Health and Medical Research Council (NHMRC) Research Fellow. iCOGS and OncoArray data: the European Community’s Seventh Framework Programme under grant agreement No. 223175 (HEALTH-F2-2009-223175) (COGS), Cancer Research UK (C1287/A10118, C1287/A 10710, C12292/A11174, C1281/A12014, C5047/A8384, C5047/A15007, C5047/A10692, C8197/A16565), the National Institutes of Health (NIH) (CA128978) and Post-Cancer GWAS initiative (1U19 CA148537, 1U19 CA148065 and 1U19 CA148112 - the GAME-ON initiative), the Department of Defence (W81XWH-10-1-0341), the Canadian Institutes of Health Research (CIHR) for the CIHR Team in Familial Risks of Breast Cancer (CRN-87521), and the Ministry of Economic Development, Innovation and Export Trade (PSR-SIIRI-701), Komen Foundation for the Cure, the Breast Cancer Research Foundation, and the Ovarian Cancer Research Fund. The Personalized Risk Stratification for Prevention and Early Detection of Breast Cancer (PERSPECTIVE) and PERSPECTIVE I&I projects were supported by the Government of Canada through Genome Canada and the Canadian Institutes of Health Research, the Ministry of Economy and Innovation through Genome Québec, and The Quebec Breast Cancer Foundation and the Ontario Research Fund. Breast Cancer Family Registry (BCFR): UM1 CA164920 from the National Cancer Institute (NCI). Baltic Familial Breast Ovarian Cancer Consortium (BFBOCC): Lithuania (BFBOCC-LT): Research Council of Lithuania grant SEN-18/2015. Beth Israel Deaconess Medical Center (BIDMC): Breast Cancer Research Foundation. BRCA-gene mutations and breast cancer in South African women (BMBSA): Cancer Association of South Africa (PI Elizabeth J. van Rensburg). Spanish National Cancer Centre (CNIO): Spanish Ministry of Health PI16/00440 supported by Fondo Europeo de Desarrollo Regional (FEDER) funds, the Spanish Ministry of Economy and Competitiveness (MINECO) SAF2014-57680-R and the Spanish Research Network on Rare diseases (CIBERER). City of Hope - Clinical Cancer Genomics Community Research Network (COH-CCGCRN): Research reported in this publication was supported by the NCI of the NIH under grant No. R25CA112486, and RC4CA153828 (PI: J. Weitzel) from the NCI and the Office of the Director, NIH. CONsorzio Studi ITaliani sui Tumori Ereditari Alla Mammella (CONSIT TEAM): Associazione Italiana Ricerca sul Cancro (AIRC; IG2014 No.15547) to P. Radice. Funds from Italian citizens who allocated the 5x1000 share of their tax payment in support of the Fondazione IRCCS Istituto Nazionale Tumori, according to Italian laws (INT-Institutional strategic projects ‘5x1000’) to S. Manoukian. Associazione CAOS Varese to M.G. Tibiletti. AIRC (IG2015 No.16732) to P. Peterlongo. National Centre for Scientific Research Demokritos (DEMOKRITOS): European Union (European Social Fund—ESF) and Greek national funds through the Operational Program “Education and Lifelong Learning” of the National Strategic Reference Framework (NSRF) - Research Funding Program of the General Secretariat for Research & Technology: SYN11_10_19 NBCA. Investing in knowledge society through the European Social Fund. German Cancer Research Center (DFKZ): German Cancer Research Center. Epidemiological Study of Familial Breast Cancer (EMBRACE): Cancer Research UK Grants C1287/A10118 and C1287/A11990. D. Gareth Evans and Fiona Lalloo are supported by an National Institute for Health Research (NIHR) grant to the Biomedical Research Centre, Manchester. The Investigators at The Institute of Cancer Research and The Royal Marsden National Health Service (NHS) Foundation Trust are supported by an NIHR grant to the Biomedical Research Centre at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust. Ros Eeles and Elizabeth Bancroft are supported by Cancer Research UK Grant C5047/A8385. Ros Eeles is also supported by NIHR support to the Biomedical Research Centre at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust. Fox Chase Cancer Center (FCCC): The University of Kansas Cancer Center (P30 CA168524) and the Kansas Bioscience Authority Eminent Scholar Program. AKG was in part funded by the NCI (R01 CA214545 and R01 CA140323), The Kansas Institute for Precision Medicine (P20 GM130423), and the Kansas Bioscience Authority Eminent Scholar Program. A.K.G. is the Chancellors Distinguished Chair in Biomedical Sciences Professor. Fundación Pública Galega de Medicina Xenómica (FPGMX): FISPI05/2275 and Mutua Madrileña Foundation (FMMA). German Familial Breast Group (GC-HBOC): German Cancer Aid (grant No. 110837, Rita K. Schmutzler) and the European Regional Development Fund and Free State of Saxony, Germany (LIFE—Leipzig Research Centre for Civilization Diseases, project No. 713-241202, No. 713-241202, No. 14505/2470, and No. 14575/2470). Genetic Modifiers of cancer risk in BRCA1/2 mutation carriers (GEMO): Ligue Nationale Contre le Cancer; the Association “Le cancer du sein, parlons-en!” Award, the Canadian Institutes of Health Research for the “CIHR Team in Familial Risks of Breast Cancer” program and the French National Institute of Cancer (INCa grants 2013-1-BCB-01-ICH-1 and SHS-E-SP 18-015). Georgetown University (GEORGETOWN): the Non-Therapeutic Subject Registry Shared Resource at Georgetown University (NIH/NCI grant P30-CA051008), the Fisher Center for Hereditary Cancer and Clinical Genomics Research, and Swing Fore the Cure. Ghent University Hospital (G-FAST): Bruce Poppe is a senior clinical investigator of FWO. Mattias Van Heetvelde obtained funding from IWT. Hospital Clinico San Carlos (HCSC): Spanish Ministry of Health PI15/00059, PI16/01292, and CB-161200301 CIBERONC from ISCIII (Spain), partially supported by European Regional Development FEDER funds. Helsinki Breast Cancer Study (HEBCS): Helsinki University Hospital Research Fund, the Finnish Cancer Society and the Sigrid Juselius Foundation. Hereditary Breast and Ovarian cancer study the Netherlands (HEBON): the Dutch Cancer Society grants NKI1998-1854, NKI2004-3088, NKI2007-3756, the Netherlands Organization of Scientific Research grant NWO 91109024, the Pink Ribbon grants 110005 and 2014-187.WO76, the Biobanking and Biomolecular Resources Research Infrastructure (BBMRI) grant NWO 184.021.007/CP46 and the Transcan grant JTC 2012 Cancer 12-054. HEBON thanks the registration teams of Dutch Cancer Registry (IKNL; S. Siesling, J. Verloop) and the Dutch Pathology database (PALGA; L. Overbeek) for part of the data collection. Study of Genetic Mutations in Breast and Ovarian Cancer patients in Hong Kong and Asia (HRBCP): Hong Kong Sanatorium and Hospital, Dr Ellen Li Charitable Foundation, The Kerry Group Kuok Foundation, National Institute of Health1R 03CA130065, and North California Cancer Center. Molecular Genetic Studies of Breast- and Ovarian Cancer in Hungary (HUNBOCS): Hungarian Research Grants KTIA-OTKA CK-80745 and NKFI_OTKA K-112228. Institut Català d’Oncologia (ICO): The authors would like to particularly acknowledge the support of the Asociación Española Contra el Cáncer (AECC), the Instituto de Salud Carlos III (organismo adscrito al Ministerio de Economía y Competitividad) and “FEDER, una manera de hacer Europa” (PI10/01422, PI13/00285, PIE13/00022, PI15/00854, PI16/00563 and CIBERONC) and the Institut Català de la Salut and Autonomous Government of Catalonia (2009SGR290, 2014SGR338 and PERIS Project MedPerCan). International Hereditary Cancer Centre (IHCC): PBZ_KBN_122/P05/2004. Iceland Landspitali – University Hospital (ILUH): Icelandic Association “Walking for Breast Cancer Research” and by the Landspitali University Hospital Research Fund. INterdisciplinary HEalth Research Internal Team BReast CAncer susceptibility (INHERIT): Canadian Institutes of Health Research for the “CIHR Team in Familial Risks of Breast Cancer” program—grant No. CRN-87521 and the Ministry of Economic Development, Innovation and Export Trade—grant No. PSR-SIIRI-701. Istituto Oncologico Veneto (IOVHBOCS): Ministero della Salute and “5x1000” Istituto Oncologico Veneto grant. Portuguese Oncology Institute-Porto Breast Cancer Study (IPOBCS): Liga Portuguesa Contra o Cancro. Kathleen Cuningham Consortium for Research into Familial Breast Cancer (kConFab): The National Breast Cancer Foundation, and previously by the National Health and Medical Research Council (NHMRC), the Queensland Cancer Fund, the Cancer Councils of New South Wales, Victoria, Tasmania and South Australia, and the Cancer Foundation of Western Australia. Korean Hereditary Breast Cancer Study (KOHBRA): the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), and the National R&D Program for Cancer Control, Ministry of Health & Welfare, Republic of Korea (HI16C1127; 1020350; 1420190). Mayo Clinic (MAYO): NIH grants CA116167, CA192393 and CA176785, an NCI Specialized Program of Research Excellence (SPORE) in Breast Cancer (CA116201), and a grant from the Breast Cancer Research Foundation. McGill University (MCGILL): Jewish General Hospital Weekend to End Breast Cancer, Quebec Ministry of Economic Development, Innovation and Export Trade. Marc Tischkowitz is supported by the funded by the European Union Seventh Framework Program (2007Y2013)/European Research Council (Grant No. 310018). Modifier Study of Quantitative Effects on Disease (MODSQUAD): MH CZ—DRO (MMCI, 00209805), MEYS—NPS I—LO1413 to LF, and by Charles University in Prague project UNCE204024 (MZ). Memorial Sloane Kettering Cancer Center (MSKCC): the Breast Cancer Research Foundation, the Robert and Kate Niehaus Clinical Cancer Genetics Initiative, the Andrew Sabin Research Fund and a Cancer Center Support Grant/Core Grant (P30 CA008748). Women’s College Research Institute Hereditary Breast and Ovarian Cancer Study (NAROD): 1R01 CA149429-01. National Cancer Institute (NCI): the Intramural Research Program of the US NCI, NIH, and by support services contracts NO2-CP-11019-50, N02-CP-21013-63 and N02-CP-65504 with Westat, Inc, Rockville, MD. National Israeli Cancer Control Center (NICCC): Clalit Health Services in Israel, the Israel Cancer Association and the Breast Cancer Research Foundation (BCRF), NY. N.N. Petrov Institute of Oncology (NNPIO): the Russian Foundation for Basic Research (grants 17-54-12007, 17-00-00171 and 18-515-12007). NRG Oncology: U10 CA180868, NRG SDMC grant U10 CA180822, NRG Administrative Office and the NRG Tissue Bank (CA 27469), the NRG Statistical and Data Center (CA 37517) and the Intramural Research Program, NCI. The Ohio State University Comprehensive Cancer Center (OSUCCG): Ohio State University Comprehensive Cancer Center. Università di Pisa (PBCS): AIRC [IG 2013 N.14477] and Tuscany Institute for Tumors (ITT) grant 2014-2015-2016. South East Asian Breast Cancer Association Study (SEABASS): Ministry of Science, Technology and Innovation, Ministry of Higher Education (UM.C/HlR/MOHE/06) and Cancer Research Initiatives Foundation. Sheba Medical Centre (SMC): the Israeli Cancer Association. Swedish Breast Cancer Study (SWE-BRCA): the Swedish Cancer Society. University of Chicago (UCHICAGO): NCI Specialized Program of Research Excellence (SPORE) in Breast Cancer (CA125183), R01 CA142996, 1U01CA161032 and by the Ralph and Marion Falk Medical Research Trust, the Entertainment Industry Fund National Women’s Cancer Research Alliance and the Breast Cancer research Foundation. OIO is an American Cancer Society (ACS) Clinical Research Professor. University of California Los Angeles (UCLA): Jonsson Comprehensive Cancer Center Foundation; Breast Cancer Research Foundation. University of California San Francisco (UCSF): UCSF Cancer Risk Program and Helen Diller Family Comprehensive Cancer Center. UK Familial Ovarian Cancer Registry (UKFOCR): Cancer Research UK. University of Pennsylvania (UPENN): NIH (R01-CA102776 and R01-CA083855); Breast Cancer Research Foundation; Susan G. Komen Foundation for the cure, Basser Research Center for BRCA. Cancer Family Registry University of Pittsburg (UPITT/MWH): Hackers for Hope Pittsburgh. Victorian Familial Cancer Trials Group (VFCTG): Victorian Cancer Agency, Cancer Australia, National Breast Cancer Foundation. Women’s Cancer Program at Cedars-Sinai Medical Center (WCP): Dr Karlan is funded by the ACS Early Detection Professorship (SIOP-06-258-01-COUN) and the National Center for Advancing Translational Sciences (NCATS), Grant UL1TR000124. TN-D is a recipient of a Career Development Fellow from the National Breast Cancer Foundation (Australia, ECF-17-001).

Psoriasis is a prevalent chronic inflammatory disease. The inflammatory response is driven by T cells and mediated by multiple cytokines such as tumor necrosis factor and the interleukins IL-17 and IL-23. Moderate-to-severe psoriasis is treated systemically, using either biologics or conventional treatments with small-molecule drugs. The newer biologics are very effective and well tolerated, but not all patients respond to treatment with biologics, so there is a need for new treatment options for psoriasis. Janus kinase (JAK) inhibitors are a new drug class that may be of use in this respect. These inhibitors are already on the market for rheumatoid arthritis, psoriatic arthritis, and ulcerative colitis. They block the intracellular signal pathway mediated by JAK and signal transducer and activator of transcription (STAT) proteins, thereby inhibiting gene transcription of proinflammatory cytokines. JAK inhibitors are currently being tested as potential treatments for psoriasis. They have shown clinical efficacy as measured by the Psoriasis Area and Severity Index 75 response in both phase 2 and 3 trials, and appear to be well tolerated overall. This review provides an overview of the mechanisms underlying the actions of JAK inhibitors in psoriasis, together with the results of clinical trials testing their efficacies when used to treat the disease.

Psoriasis is linked with increased risk of cardiovascular disease (CVD) that is underestimated by traditional risk stratification. We conducted a large-scale plasma proteomic analysis by use of a proximity extension assay in 85 patients with a history of moderate-to-severe psoriasis with or without established atherosclerotic CVD. Differentially expressed proteins associated with CVD were correlated with subclinical atherosclerotic markers including vascular inflammation determined by 18F-fluorodeoxyglucose positron emission tomography/computed tomography, carotid intima-media thickness (CIMT), carotid artery plaques, and coronary artery calcium score (CCS) in the patients without CVD and statin treatment. We also examined the association between the neutrophil-to-lymphocyte ratio (NLR) and subclinical atherosclerosis. In unadjusted analyses, growth differentiation factor-15 (GDF-15) levels and NLR were increased, while tumor necrosis factor (TNF)-related activation-inducing ligand (TRANCE) and TNF-related apoptosis-induced ligand (TRAIL) levels were decreased in patients with established CVD compared to those without CVD. Among patients with psoriasis without CVD and statin treatment, GDF-15 levels were negatively associated with vascular inflammation in the ascending aorta and entire aorta, and positively associated with CIMT and CCS. NLR was positively associated with vascular inflammation in the carotid arteries. Our data suggest that circulating GDF-15 levels and NLR might serve as biomarkers of subclinical atherosclerosis in patients with psoriasis.

Hereditary Polyposis Syndromes are a group of rare, inherited syndromes characterized by the presence of histopathologically specific or numerous intestinal polyps and an increased risk of cancer. Some polyposis syndromes have been known for decades, but the development in genetic technologies has allowed the identification of new syndromes.. The diagnosis entails surveillance from an early age, but universal guideline on how to manage and surveille these new syndromes are lacking. This paper represents a condensed version of the recent guideline (2020) from a working group appointed by the Danish Society of Medical Genetics and the Danish Society of Surgery on recommendations for the surveillance of patients with hereditary polyposis syndromes, including rare polyposis syndromes. Supplementary Information The online version contains supplementary material available at 10.1186/s13053-021-00197-8.

Aims A higher surgical trainee combatted patients’ deaths and disasters from COVID-19. The trainee treated daily COVID-19-positive patients. In May 2020, he recognized symptoms of COVID-19. Throat swab test confirmed the suspicion of contagion. We aimed to study the acute stress disorder (ASD) during the COVID-19 pandemic in the surgical trainee. Methods The case self-isolated for 2 weeks with an intensifying fear of health deterioration. The case’s isolation and feelings of being in poor health, opened for an e-mail therapy. Sixty open-ended questions were answered in Socratic-maieutic style. The finding of severe (ASD) was validated and confirmed by use of the National Stressful Events Survey Acute Stress Disorder Short Scale. The mail therapy continued until the case felt that the crisis had faded. After 10 weeks a follow up was completed A, B and C times for 7 issues: death anxiety, worries about family after own death, chest pressure, other physical symptoms, stress, depression, other psychological symptoms Results Our hypothesis was termed “acute stress reactions”. Our case’s ASD was categorized as “severe”. Friedman test was applied for the related groups A, B and C, indicating an overall symptom improvement (p < .001) which by Page’s L trend test disclosed a significant trend in symptom cutback from A to C (p < .001). Conclusion The surgeons’ awareness is required that in some cases, the psychological symptoms escalate during isolation and quarantine periods and may even override the physical awkwardness, urging us to address both types of discomfort simultaneously and intensely.

Background: Patients with psoriasis have an increased risk of atherosclerotic cardiovascular disease (CVD). The molecular mechanisms behind this connection are not fully understood, but the involvement of neutrophils have drawn attention as a shared inflammatory factor. Methods: RNA sequencing using the Illumina platform was performed on blood from 38 patients with moderate to severe psoriasis, approximately half had prior CVD. The neutrophil to lymphocyte ratio (NLR) was obtained from blood samples. Subclinical atherosclerosis was assessed by 18F-fluorodeoxyglucose positron emission tomography/computed tomography and ultrasound imaging. Transcriptomic analysis for differential expression and functional enrichment were performed, followed by correlation analyses of differentially expressed genes (DEGs), NLR and subclinical measurers of CVD. Results: 291 genes were differentially expressed between patients with psoriasis with and without CVD. These included 208 upregulated and 83 downregulated DEGs. Neutrophil degranulation was identified as the most significant process related to the upregulated DEGs. Genes for the neutrophil-associated markers MPO, MMP9, LCN2, CEACAM1, CEACAM6 and CEACAM8 were identified as being of special interest and their mRNA levels correlated with NLR, high-sensitive C-reactive protein and markers of subclinical CVD. Conclusions: Patients with psoriasis and CVD had an increased expression of genes related to neutrophil degranulation in their blood transcriptome compared with patients with psoriasis without CVD. NLR may be a potential biomarker of subclinical CVD in psoriasis.

ObjectivesTo describe the prevalence of comorbidities in a population referred to standardised first-line intervention (patient education and exercise) for hip and knee osteoarthritis (OA), in comparison with the general population. Furthermore, we aimed to evaluate if eventual differences were associated with socioeconomic inequalities.DesignRegister-based study.SettingPrimary healthcare, Sweden.ParticipantsIndividuals with hip and/or knee OA included in the Better Management for Patients with Osteoarthritis Register between 2008 and 2016 and and an age-matched, sex-matched and residence-matched reference cohort (1:3) from the general Swedish population.Outcome measuresComorbidities were identified with the RxRisk Index, the Elixhauser Comorbidity Index and the Charlson Comorbidity Index, and presented with descriptive statistics as (1) individual diseases, (2) disease categories and (3) scores for each index. The prevalence of comorbidities in the two populations was tested using logistic regression, with separate analyses for age groups and the most affected joint. We then adjusted the analyses for socioeconomic status.ResultsIn this OA population, 85% had ≥1 comorbidity compared with 78% of the reference cohort (OR; 1.62 (95% CI 1.59 to 1.66)). Cardiovascular/blood diseases were the most common comorbidities in both populations (OA, 59%; reference, 54%), with OR; 1.22 (95% CI 1.20 to 1.24) for the OA population. Younger individuals with OA were more comorbid than their matched references overall, and population differences decreased with age (eg, ≥3 comorbidities, aged ≤45 years OR; 1.74 (95% CI 1.52 to 1.98), ≥81 years OR; 0.95 (95% CI 0.87 to 1.04)). Individuals with knee OA were more comorbid than those with hip OA overall. Adjustment for socioeconomic status did not change the estimates.ConclusionComorbidities were more common among individuals with hip and knee OA than among matched references from the general population. The differences could not be explained by socioeconomic status.Trial registration numberNCT03438630.

During the outbreak of the COVID-19 pandemic, guidelines have been issued by international, national and local authorities to address management and the need for preparedness. Children with COVID-19 differ from adults in that they are less often and less severely affected. Additional precautions required in the management of children address their increased radiosensitivity, need for accompanying carers, and methods for dealing with children in a mixed adult-paediatric institution. In this guidance document, our aim is to define a pragmatic strategy for imaging children with an emphasis on proven or suspected COVID-19 cases. Children suspected of COVID-19 should not be imaged routinely. Imaging should be performed only when expected to alter patient management, depending on symptoms, preexisting conditions and clinical evolution. In order to prevent disease transmission, it is important to manage the inpatient caseload effectively by triaging children and carers outside the hospital, re-scheduling nonurgent elective procedures and managing symptomatic children and carers as COVID-19 positive until proven otherwise. Within the imaging department one should consider conducting portable examinations with COVID-19 machines or arranging dedicated COVID-19 paediatric imaging sessions and performing routine nasopharyngeal swab testing before imaging under general anaesthesia. Finally, regular personal hygiene, appropriate usage of personal protective equipment, awareness of which procedures are considered aerosol generating and information on how to best disinfect imaging machinery after examinations should be highlighted to all staff members. Electronic supplementary material The online version of this article (10.1007/s00247-020-04749-3) contains supplementary material, which is available to authorized users.

Purpose: In recent years, there has been a significant increase in referrals for gender-affirming surgery to departments of plastic surgery in Denmark. There is currently no literature on postsurgical pain in trans men after mastectomy. We aimed at investigating the prevalence and severity of postsurgical persistent pain, sensory disturbances, and complications in trans men after mastectomy. Methods: The 90 trans men who underwent bilateral mastectomy between September 1, 2013 and August 31, 2018 were included. Patients' files were evaluated for complications, and 84 (response rate 93.3%) patients answered a questionnaire (validated for women undergoing oncologic mastectomy) regarding persistent pain and sensory disturbances. Results: Twenty-three patients (27.4%) reported either unilateral or bilateral persistent pain after mastectomy. Of these, 14 (60.9%) patients categorized the pain as mild. However, 77 (95.2%) of the patients did not use analgesics and nonopioid pain medication was sufficient for the remainder. Sensory disturbances were found in 44 (47.5%) of the patients, and 4 (4.8%) patients reported clear signs of neuropathic pain. Seven (7.8%) patients developed hematomas, and areola necrosis was seen in four (4.4%) patients. Due to infection, seven (7.8%) patients received antibiotics. Conclusion: Mastectomy as a part of gender-affirming surgery is a safe procedure with a few, nonsevere, complications. Although a quarter of the patients experienced persistent pain, the majority of that pain is mild, intermittent and can be treated with nonopioid pain medication.

Made available in DSpace on 2021-06-25T11:16:28Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-01-01 Agence Nationale Des Parcs Nationaux Centre for International Forestry Research Departamento Administrativo de Ciencia, Tecnología e Innovación (COLCIENCIAS) David and Lucile Packard Foundation European Space Agency Leverhulme Trust Gordon and Betty Moore Foundation Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Fundação de Amparo à Pesquisa do Estado de Goiás European Research Council Belgian Federal Science Policy Office Vlaamse Interuniversitaire Raad Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) National Science Foundation Natural Environment Research Council Royal Society National Geographic Society Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) Tropical forests are the most diverse and productive ecosystems on Earth. While better understanding of these forests is critical for our collective future, until quite recently efforts to measure and monitor them have been largely disconnected. Networking is essential to discover the answers to questions that transcend borders and the horizons of funding agencies. Here we show how a global community is responding to the challenges of tropical ecosystem research with diverse teams measuring forests tree-by-tree in thousands of long-term plots. We review the major scientific discoveries of this work and show how this process is changing tropical forest science. Our core approach involves linking long-term grassroots initiatives with standardized protocols and data management to generate robust scaled-up results. By connecting tropical researchers and elevating their status, our Social Research Network model recognises the key role of the data originator in scientific discovery. Conceived in 1999 with RAINFOR (South America), our permanent plot networks have been adapted to Africa (AfriTRON) and Southeast Asia (T-FORCES) and widely emulated worldwide. Now these multiple initiatives are integrated via ForestPlots.net cyber-infrastructure, linking colleagues from 54 countries across 24 plot networks. Collectively these are transforming understanding of tropical forests and their biospheric role. Together we have discovered how, where and why forest carbon and biodiversity are responding to climate change, and how they feedback on it. This long-term pan-tropical collaboration has revealed a large long-term carbon sink and its trends, as well as making clear which drivers are most important, which forest processes are affected, where they are changing, what the lags are, and the likely future responses of tropical forests as the climate continues to change. By leveraging a remarkably old technology, plot networks are sparking a very modern revolution in tropical forest science. In the future, humanity can benefit greatly by nurturing the grassroots communities now collectively capable of generating unique, long-term understanding of Earth's most precious forests. Resumen: Los bosques tropicales son los ecosistemas más diversos y productivos del mundo y entender su funcionamiento es crítico para nuestro futuro colectivo. Sin embargo, hasta hace muy poco, los esfuerzos para medirlos y monitorearlos han estado muy desconectados. El trabajo en redes es esencial para descubrir las respuestas a preguntas que trascienden las fronteras y los plazos de las agencias de financiamiento. Aquí mostramos cómo una comunidad global está respondiendo a los desafíos de la investigación en ecosistemas tropicales a través de diversos equipos realizando mediciones árbol por árbol en miles de parcelas permanentes de largo plazo. Revisamos los descubrimientos más importantes de este trabajo y discutimos cómo este proceso está cambiando la ciencia relacionada a los bosques tropicales. El enfoque central de nuestro esfuerzo implica la conexión de iniciativas locales de largo plazo con protocolos estandarizados y manejo de datos para producir resultados que se puedan trasladar a múltiples escalas. Conectando investigadores tropicales, elevando su posición y estatus, nuestro modelo de Red Social de Investigación reconoce el rol fundamental que tienen, para el descubrimiento científico, quienes generan o producen los datos. Concebida en 1999 con RAINFOR (Suramérica), nuestras redes de parcelas permanentes han sido adaptadas en África (AfriTRON) y el sureste asiático (T-FORCES) y ampliamente replicadas en el mundo. Actualmente todas estas iniciativas están integradas a través de la ciber-infraestructura de ForestPlots.net, conectando colegas de 54 países en 24 redes diferentes de parcelas. Colectivamente, estas redes están transformando nuestro conocimiento sobre los bosques tropicales y el rol de éstos en la biósfera. Juntos hemos descubierto cómo, dónde y porqué el carbono y la biodiversidad de los bosques tropicales está respondiendo al cambio climático y cómo se retroalimentan. Esta colaboración pan-tropical de largo plazo ha expuesto un gran sumidero de carbono y sus tendencias, mostrando claramente cuáles son los factores más importantes, qué procesos se ven afectados, dónde ocurren los cambios, los tiempos de reacción y las probables respuestas futuras mientras el clima continúa cambiando. Apalancando lo que realmente es una tecnología antigua, las redes de parcelas están generando una verdadera y moderna revolución en la ciencia tropical. En el futuro, la humanidad puede beneficiarse enormemente si se nutren y cultivan comunidades de investigadores de base, actualmente con la capacidad de generar información única y de largo plazo para entender los que probablemente son los bosques más preciados de la tierra. Resumo: Florestas tropicais são os ecossistemas mais diversos e produtivos da Terra. Embora uma boa compreensão destas florestas seja crucial para o nosso futuro coletivo, até muito recentemente os esforços de medições e monitoramento foram amplamente desconexos. É essencial formarmos redes para obtermos respostas que transcendem fronteiras e horizontes de agências financiadoras. Neste estudo nós mostramos como uma comunidade global está respondendo aos desafios da pesquisa de ecossistemas tropicais, com equipes diversas medindo florestas, árvore por árvore, em milhares de parcelas monitoradas à longo prazo. Nós revisamos as maiores descobertas científicas deste trabalho, e mostramos também como este processo está mudando a ciência de florestas tropicais. Nossa abordagem principal envolve unir iniciativas de base a protocolos padronizados e gerenciamento de dados a fim de gerar resultados robustos em escalas ampliadas. Ao conectar pesquisadores tropicais e elevar seus status, nosso modelo de Rede de Pesquisa Social reconhece o papel-chave do produtor dos dados na descoberta científica. Concebida em 1999 com o RAINFOR (América do Sul), nossa rede de parcelas permanentes foi adaptada para África (AfriTRON) e Sudeste asiático (T-FORCES), e tem sido extensamente reproduzida em todo o mundo. Agora estas múltiplas iniciativas estão integradas através de uma infraestrutura cibernética do ForestPlots.net, conectando colegas de 54 países de 24 redes de parcelas. Estas iniciativas estão transformando coletivamente o entendimento das florestas tropicais e seus papéis na biosfera. Juntos nós descobrimos como, onde e por que o carbono e a biodiversidade da floresta estão respondendo às mudanças climáticas, e seus efeitos de retroalimentação. Esta duradoura colaboração pantropical revelou um grande sumidouro de carbono persistente e suas tendências, assim como tem evidenciado quais direcionadores são mais importantes, quais processos florestais são mais afetados, onde eles estão mudando, seus atrasos no tempo de resposta, e as prováveis respostas das florestas tropicais conforme o clima continua a mudar. Dessa forma, aproveitando uma notável tecnologia antiga, redes de parcelas acendem faíscas de uma moderna revolução na ciência das florestas tropicais. No futuro a humanidade pode se beneficiar incentivando estas comunidades basais que agora são coletivamente capazes de gerar conhecimentos únicos e duradouros sobre as florestas mais preciosas da Terra. Résume: Les forêts tropicales sont les écosystèmes les plus diversifiés et les plus productifs de la planète. Si une meilleure compréhension de ces forêts est essentielle pour notre avenir collectif, jusqu'à tout récemment, les efforts déployés pour les mesurer et les surveiller ont été largement déconnectés. La mise en réseau est essentielle pour découvrir les réponses à des questions qui dépassent les frontières et les horizons des organismes de financement. Nous montrons ici comment une communauté mondiale relève les défis de la recherche sur les écosystèmes tropicaux avec diverses équipes qui mesurent les forêts arbre après arbre dans de milliers de parcelles permanentes. Nous passons en revue les principales découvertes scientifiques de ces travaux et montrons comment ce processus modifie la science des forêts tropicales. Notre approche principale consiste à relier les initiatives de base à long terme à des protocoles standardisés et une gestion de données afin de générer des résultats solides à grande échelle. En reliant les chercheurs tropicaux et en élevant leur statut, notre modèle de réseau de recherche sociale reconnaît le rôle clé de l'auteur des données dans la découverte scientifique. Conçus en 1999 avec RAINFOR (Amérique du Sud), nos réseaux de parcelles permanentes ont été adaptés à l'Afrique (AfriTRON) et à l'Asie du Sud-Est (T-FORCES) et largement imités dans le monde entier. Ces multiples initiatives sont désormais intégrées via l'infrastructure ForestPlots.net, qui relie des collègues de 54 pays à travers 24 réseaux de parcelles. Ensemble, elles transforment la compréhension des forêts tropicales et de leur rôle biosphérique. Ensemble, nous avons découvert comment, où et pourquoi le carbone forestier et la biodiversité réagissent au changement climatique, et comment ils y réagissent. Cette collaboration pan-tropicale à long terme a révélé un important puits de carbone à long terme et ses tendances, tout en mettant en évidence les facteurs les plus importants, les processus forestiers qui sont affectés, les endroits où ils changent, les décalages et les réactions futures probables des forêts tropicales à mesure que le climat continue de changer. En tirant parti d'une technologie remarquablement ancienne, les réseaux de parcelles déclenchent une révolution très moderne dans la science des forêts tropicales. À l'avenir, l'humanité pourra grandement bénéficier du soutien des communautés de base qui sont maintenant collectivement capables de générer une compréhension unique et à long terme des forêts les plus précieuses de la Terre. Abstrak: Hutan tropika adalah di antara ekosistem yang paling produktif dan mempunyai kepelbagaian biodiversiti yang tinggi di seluruh dunia. Walaupun pemahaman mengenai hutan tropika amat penting untuk masa depan kita, usaha-usaha untuk mengkaji dan mengawas hutah-hutan tersebut baru sekarang menjadi lebih diperhubungkan. Perangkaian adalah sangat penting untuk mencari jawapan kepada soalan-soalan yang menjangkaui sempadan dan batasan agensi pendanaan. Di sini kami menunjukkan bagaimana sebuah komuniti global bertindak balas terhadap cabaran penyelidikan ekosistem tropika melalui penglibatan pelbagai kumpulan yang mengukur hutan secara pokok demi pokok dalam beribu-ribu plot jangka panjang. Kami meninjau semula penemuan saintifik utama daripada kerja ini dan menunjukkan bagaimana proses ini sedang mengubah bidang sains hutan tropika. Teras pendekatan kami memberi tumpuan terhadap penghubungan inisiatif akar umbi jangka panjang dengan protokol standar serta pengurusan data untuk mendapatkan hasil skala besar yang kukuh. Dengan menghubungkan penyelidik-penyelidik tropika dan meningkatkan status mereka, model Rangkaian Penyelidikan Sosial kami mengiktiraf kepentingan peranan pengasas data dalam penemuan saintifik. Bermula dengan pengasasan RAINFOR (Amerika Selatan) pada tahun 1999, rangkaian-rangkaian plot kekal kami kemudian disesuaikan untuk Afrika (AfriTRON) dan Asia Tenggara (T-FORCES) dan selanjutnya telah banyak dicontohi di seluruh dunia. Kini, inisiatif-inisiatif tersebut disepadukan melalui infrastruktur siber ForestPlots.net yang menghubungkan rakan sekerja dari 54 negara di 24 buah rangkaian plot. Secara kolektif, rangkaian ini sedang mengubah pemahaman tentang hutan tropika dan peranannya dalam biosfera. Kami telah bekerjasama untuk menemukan bagaimana, di mana dan mengapa karbon serta biodiversiti hutan bertindak balas terhadap perubahan iklim dan juga bagaimana mereka saling bermaklum balas. Kolaborasi pan-tropika jangka panjang ini telah mendedahkan sebuah sinki karbon jangka panjang serta arah alirannya dan juga menjelaskan pemandu-pemandu perubahan yang terpenting, di mana dan bagaimana proses hutan terjejas, masa susul yang ada dan kemungkinan tindakbalas hutan tropika pada perubahan iklim secara berterusan di masa depan. Dengan memanfaatkan pendekatan lama, rangkaian plot sedang menyalakan revolusi yang amat moden dalam sains hutan tropika. Pada masa akan datang, manusia sejagat akan banyak mendapat manfaat jika memupuk komuniti-komuniti akar umbi yang kini berkemampuan secara kolektif menghasilkan pemahaman unik dan jangka panjang mengenai hutan-hutan yang paling berharga di dunia. Instituto de Ecología Regional (IER) Universidad Nacional de Tucumán (UNT) Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET) Facultad de Ciencias Agrarias Universidad Nacional de Jujuy James Cook University (JCU) CSIRO (Commonwealth Scientific and Industrial Research Organisation) School of Land & Food University of Tasmania CSIRO Tropical Forest Research Centre Independent Researcher Environmental Protection Agency (EPA) Centre for Tropical Environmental and Sustainability Science (TESS) College of Marine and Environmental Sciences James Cook University Centre for Tropical Environmental and Sustainability Science College of Science and Engineering James Cook University University of the Sunshine Coast University of York Flamingo Land Ltd. Sommersbergseestrasse Ghent University CAVElab Ghent University Royal Museum for Central Africa - Service of Wood Biology Isotope Bioscience Laboratory-ISOFYS Ghent University Gembloux Agro-Bio Tech Université de Liege Landscape Ecology and Vegetal Production Systems Unit CAVElab Computational & Applied Vegetation Ecology Ghent University Tropical Forestry Forest Resources Management Gembloux Agro-Bio Tech University of Liege Université Libre de Bruxelles (ULB) Evolutionary Biology and Ecology Royal Museum for Central Africa Royal Museum for Central Africa Ghent University Department of Environment Ghent University Service Evolution Biologique et Ecologie Belize Foundation for Research and Environmental Education IBIF Museo de Historia Natural Noel Kempff Mercado Universidad Autonoma Gabriel Rene Moreno PROMAB Museo Noel Kempff Consultor Independiente Jardin Botanico Municipal de Santa Cruz Museo de Historia Natural Noel Kempff Mercado Forest Management in Bolivia Universidad Autónoma del Beni Riberalta Museo de Historia Natural Noel Kempff Herbario del Sur de Bolivia Universidad Autónoma del Beni Conservation International Instituto de Biodiversidade e Floresta Universidade Federal do Oeste do Pará Universidade Federal de Pernambuco Universidade do Estado de Mato Grosso Universidade do Estado de Mato Grosso (UNEMAT) Projeto TEAM – Manaus Universidade Federal de Juiz de Fora (UFJF) Universidade Federal do Rio de Janeiro Instituto Nacional de Pesquisas da Amazônia Projeto Dinâmica Biológica de Fragmentos Florestais Departamento de Genética Ecologia e Evolução Universidade Federal de Minas Gerais Universidade Estadual de Campinas Laboratório de Ecologia de Comunidades e Funcionamento de Ecossistemas-ECoFERP Departamento de Biologia Faculdade de Filosofia Ciências e Letras USP National Institute for Space Research (INPE) Universidade Federal de Roraima (UFRR) UNESP - São Paulo State University Carbonozero Consultoria Ambiental Departamento de Biologia Universidade Federal do Amazonas (UFAM) Centro de Energia Nuclear na Agricultura Universidade de São Paulo UERR - Campus Rorainópolis Universidade Federal do Acre Instituto Agronômico de Campinas Universidade Federal do Rio Grande do Sul Embrapa Universidade Estadual do Norte Fluminense (UENF) Universidade Federal da Bahia (UFBA) Instituto de Biologia Universidade Estadual de Campinas Universidade Federal do Piauí (UFPI) Botany and Plant Ecology Laboratory Federal University of Acre INPA- Instituto Nacional de Pesquisas da Amazônia UERR - Campus Boa Vista Universidade Federal do Ceará Universidade Federal de Campina Grande Universidade Federal do Para Núcleo de Estudos e Pesquisas Ambientais Universidade Estadual de Campinas Instituto Federal de Educação Ciência e Tecnologia do Acre Instituto de Pesquisas Jardim Botânico do Rio de Janeiro Universidade Federal do Oeste do Pará UEFS Depto. de Ciências Biológicas Universidade Federal do Agreste de Pernambuco (UFAPE) Universidade Estadual de Montes Claros FFCLRP-USP/Br UNEMAT Universidade Federal de Jataí Universidade Federal do Pará Instituto de Ciências Biológicas Universidade de Campinas Universidade Federal de Lavras (UFLA) Museu Goeldi Embrapa Amazônia Oriental Instituto Nacional de Pesquisas da Amazônia UFMG - Universidade Federal de Minas Gerais Fundação Universidade Fedral de Rondônia - UNIR INPA- Instituto Nacional de Pesquisas Amazônicas Instituto Nacional de Pesquisas da Amazônia - Coordenação de Pesquisas em Silvicultura Tropical Jardim Botânico do Rio de Janeiro National Institute for Research in Amazonia Universidade Federal de Roraima (UFRR/PRONAT) Universidade Estadual de Campinas/UNICAMP Instituto Nacional de Pesquisas da Amazônia/CPBO Universidade Federal de Santa Catarina (UFSC) INCAPER- Instituto Capixaba de Pesquisa Assistência Técnica e Extensão Rural INPE- Instituto Nacional de Pesquisas Espaciais Universidade de São Paulo Instituto de Biociências Universidade Estadual Paulista Semiarid National Institute (INSA) Universidade de Brasília Departamento de Engenharia Florestal IBAM - Instituto Bem Ambiental Universidade do Estado de Mato Grosso Campus de Nova Xavantina University in Campinas Universidade Estadual do Norte Fluminense Darcy Ribeiro (UENF) LMF Instituto Nacional de Pesquisas da Amazônia Universidade Federal do Vale do São Francisco USP - University of São Paulo Instituto Federal do Espírito Santo (IFES) INPA - Instituto Nacional de Pesquisas da Amazônia Grupo MAUA Universidade Federal de Mato Grosso Instituto de Ciências Naturais Humanas e Sociais Instituto Nacional da Mata Atlântica RAINFOR-PPBIO Universidade Federal Rural da Amazônia - UFRA/CAPES Universidade Federal do Amazonas (UFAM) INPA/Max-Planck Project EMBRAPA- Empresa Brasileira de Pesquisa Agropecuária (Amazônia Oriental) Serviço Florestal Brasileiro Museu Universitário Universidade Federal do Acre Universidade Federal Rural de Pernambuco PUCPR - Pontifícia Universidade Católica do Paraná Museu Paraense Emilio Goeldi Universiti Brunei Darussalam Environmental and Life Sciences Faculty of Science Universiti Brunei Darussalam Institute for Biodiversity and Environmental Research Universiti Brunei Darussalam Plant Systematic and Ecology Laboratory Department of Biology Higher Teachers’ Training College University of Yaounde I Faculty of Science Department of Botany and Plant Physiology University of Buea Faculty of Science Department of Plant Science University of Buea National Herbarium Plant Systematics and Ecology Laboratory Higher Teachers’ Training College University of Yaoundé I Department of Plant Biology Faculty of Sciences University of Yaounde 1 Bioversity International Faculty of Forestry University of Toronto Ministère des Eaux Forêts Chasse et Pêche (MEFCP) Universidad Católica de la Santísima Concepción Universidad de La Serena Research Institute of Tropical Forestry Chinese Academy of Forestry Kunming Institute of Botany Chinese Academy of Sciences Beijing Forestry University Universidad Nacional Abierta y a Distancia Red COL-TREE Corporación COL-TREE Nuevo Estándar Biotropical NEBIOT SAS Universidad del Tolima Asociación GAICA Universidad de Nariño – Red BST-Col Parques Nacionales Naturales Territorial Caribe – Red BST-Col Universidad del Atlantico – Red BST-Col Departamento de Ciencias Forestales Universidad Nacional de Colombia - Sede Medellín Socioecosistemas y Clima Sostenible Fundacion con Vida Parques Nacionales Naturales de Colombia – Red BST-Col Instituto de Investigación de Recursos Biológicos Alexander von Humboldt – Red BST-Col UNAL Instituto de Investigación Recursos Biologicos Alexander von Humboldt – Red BST-Col Fundación Jardín Botánico de Medellín Herbario “Joaquín Antonio Uribe” (JAUM) – Red BST-Col Universidad Nacional de Colombia sede Amazonia Coltree Facultad del Medio Ambiente y Recursos Naturales Universidad Distrital Francisco José de Caldas – Red BST-Col Universidad de Tolima Fundación Orinoquia Biodiversa – Red BST-Col Departamento de Biología Facultad de Ciencias Naturales Universidad Icesi – Red BST-Col Instituto de Ciencias Naturales Universidad Nacional de Colombia Universidad de los Llanos Servicios Ecoysistemicos y Cambio Climatico (SECC) Fundación Con Vida & Corporación COL-TREE Universidad del Rosario Fundacion Ecosistemas Secos de Colombia – Red BST-Col Universidad de los Andes - ANDES herbarium Institute of Botany Czech Academy of Sciences Palacky University Czech University of Life Sciences Mendel University World Wide Fund for Nature Wildlife Conservation Society-DR Congo Lukuru Wildlife Research Foundation Université de Kisangani Faculté des Sciences Laboratoire d'écologie et aménagement forestier Université de Kisangani Université de Kisangani Faculté des Sciences Agronomiques République Démocratique du Congo Ministère de l'Environnement et Développement Durable Aarhus University University of Copenhagen Escuela Politécnica Nacional del Ecuador Herbario Alfredo Paredes (QAP) Universidad Central del Ecuador Universidad Técnica Particular de Loja Grupo de Investigación en Biodiversidad Medio Ambiente y Salud-BIOMAS Universidad de las Américas, Campus Queri Keller Science Action Center The Field Museum, 1400 South Lake Shore Dr. Universidad Estatal Amazónica Facultad de Ingeniería Ambiental Universidad Tecnica del Norte Herbario Nacional del Ecuador Grupo de Ecosistemas Tropicales y Cambio Global Universidad Regional Amazónica ikiam Colegio de Ciencias Biológicas y Ambientales COCIBA & Extensión Galápagos Universidad San Francisco de Quito-USFQ Herbario de Botánica Económica del Ecuador QUSF Universidad San Francisco de Quito USFQ Galapagos Science Center USFQ UNC Chapel Hill University of North Carolina-UNC Chapel Hill University of Florida FindingSpecies Mekelle University Environment Climate Change and Coffee Forest Forum (ECCCFF) University of Turku Centre de coopération International en Recherche Agronomique pour le Développement (CIRAD) CNRS ONF INRAE Centre National de la Recherche Scientifique AMAP Univ Montpellier IRD CNRS CIRAD INRA Forêts et Sociétés (F&S) Centre de coopération International en Recherche Agronomique pour le Développement (CIRAD) Departement Hommes Natures Societes Museum national d'histoire naturelle INRA Cirad UMR Ecologie des Forêts de Guyane (AgroparisTech CNRS INRAE Université des Antilles Université de la Guyane) Ministry of Forests Seas Environment and Climate Rougier-Gabon Agence Nationale des Parcs Nationaux Gabon Commission of Central African Forests (COMIFAC) Agence Nationale des Parcs Nationaux Ministère des Forêts des Eaux de la Mer de l'Environnement Chargé du Plan Climat des Objectifs de Développement Durable et du Plan d'Affectation des Terres Institut de Recherche en Ecologie Tropicale (CENAREST) Gabon/Agence Nationale des Parcs Nationaux Georg-August-University Göttingen University of Freiburg Institute of Botany University of Hohenheim Max Planck Institute for Chemistry Forestry Research Institute of Ghana (FORIG) Mensuration Unit Forestry Commission of Ghana Center for International Forestry Research Iwokrama International Centre for Rainforest Conservation and Development Guyana Forestry Commission Utrecht University Centre for Sustainable Technologies Indian Institute of Science Centre for International Forestry Research (CIFOR) Herbarium Borgoriense Indonesian Institute of Sciences (LIPI) Indonesian Institute of Science Forest Research and Development Agency (FORDA) Balitek-KSDA Samboja University of Florence and MUSE - Museo delle Scienze Cirad Hokkaido University Graduate School of Agriculture Kyoto University Forestry Development Authority of the Government of Liberia (FDA) University of Liberia Sungai Wain Protection Forest South East Asia Rainforest Research Partnership Danum Valley Field Centre Malaysian Palm Oil Board Sabah Forestry Department Forest Research Centre Universiti Malaysia Sabah Sabah Forestry Department Sarawak Forestry Corporation Eduardo Mondlane University Herbarium UNAN-Leon Universidad Nacional Autónoma de Nicaragua University of Abeokuta Natural History Museum of Norway University of Oslo Norwegian University of Life Sciences Universidad Nacional de la Amazonía Peruana (UNAP) Universidad Nacional de Jaén Jardin Botanico de Missouri Andes to Amazon Biodiversity Program Universidad Nacional de San Agustín de Arequipa Facultad de Ciencias Biológicas Universidad Nacional de la Amazonía Peruana Kené - Instituto de Estudios Forestales y Ambientales Instituto de Investigaciones de la Amazonia Peruana (IIAP) Universidad Nacional Jorge Basadre de Grohmann (UNJBG) Universidad Nacional de San Antonio Abad del Cusco Centro de Conservación Investigación y Manejo CIMA Pontificia Universidad Católica del Perú Asociacion Bosques Perú Université Officielle de Bukavu Université Marien N'Gouabi Wildlife Conservation Society Ecole Nationale Supérieure d'Agronomie et de Foresterie Université Marien Ngouabi Univeriste Marien Ngouabi The Gola Rainforest National Park Department of Geography National University of Singapore Departamento de Biología y Geología Física y Química inorgánica Universidad Rey Juan Carlos Real Jardín Botánico – CSIC Departamento de Biología Área de Botánica Universidad Autónoma de Madrid Museo Nacional de Ciencias Naturales (MNCN-CSIC) Centre for Agricultural Research in Suriname (CELOS) Stockholm Environment Institute Department of Plant Ecology and Evolution Uppsala University Southern Swedish Forest Research Centre InfoFlora Conservatoire et Jardin Botanique Geneve National Chung Hsing University Sokoine University of Agriculture Naturalis Biodiversity Center Wageningen University Forest Ecology and Forest Management Group Tropenbos International Institute for Biodiversity and Ecosystem Dynamics University of Amsterdam Bureau Waardenburg BV Van Hall Larenstein University of Applied Sciences Van der Hout Forestry Consulting Utrecht University, Domplein 29 Wageningen University Plant Ecology and Nature Conservation Group Data for Sustainability Department of Zoology Entomology & Fisheries Sciences Makerere University The Institute of Tropical Forest Conservation (ITFC) Mbarara University of Science and Technology (MUST) George Washington University Makerere University Department of Forestry Biodiversity and Tourism Makerere University University of Stirling University of Kent School of Geography University of Leeds UK Centre of Ecology & Hydrology Lancaster University University of Oxford The Landscapes and Livelihoods Group (TLLG) Overseas Development Institute Manchester Metropolitan University University of Aberdeen University of Exeter School of GeoSciences University of Edinburgh University of Cambridge Department of Environment and Geography University of York Department of Geography University College London Imperial College School of Geography Earth & Environmental Sciences Birmingham Institute of Forest Research University of Birmingham University of Plymouth Geography College of Life and Environmental Sciences University of Exeter Lancaster Environment Centre Lancaster University University of Edinburgh School of Biology University of Leeds Royal Botanic Garden Edinburgh CENAREST & ANPN & Stirling University University of Bristol School of Biological Sciences Department of Plant Sciences University of Cambridge Living with Lake Centre Laurentian University Royal Botanic Gardens Kew The Royal Society for the Protection of Birds centre for Conservation Science Environmental Change Institute School of Geography and the Environment University of Oxford UK Centre for Ecology & Hydrology School of Geography and the Environment University of Oxford The Royal Botanic Gardens Department of Geography and Environmental Science University of Dundee School of Biological Sciences University of Southampton University of East Anglia Stirling University School of Earth and Environment University of Leeds Department of Plant & Soil Science School of Biological Sciences University of Aberdeen, Cruickshank Building Institute for Transport Studies University of Leeds UK Research & Innovation University of Nottingham University of Bangor Center for Tropical Research Institute of the Environment and Sustainability University of California Center for Tropical Conservation Nicholas School of the Environment Duke University Ecology and Evolutionary Biology University of Michigan Saint Louis Zoo Department of Organismic and Evolutionary Biology Harvard University Center for Global Discovery and Conservation Science Arizona State University Wildlife Conservation Society – Programme Congo Woods Hole Research Center The University of Michigan Herbarium Nicholas School of the Environment National Park Service University of California ForestGEO Smithsonian Tropical Research Institute University of Texas at Austin Smithsonian Institute Washington University in Saint Louis Center for Conservation and Sustainable Development at the Missouri Botanical Garden Smithsonian Tropical Research Institute Smithsonian Institution Forest Global Earth Observatory (ForestGEO) Forest Global Earth Observatory (ForestGEO) Smithsonian Tropical Research Institute George Mason University Missouri Botanical Garden Broward County Parks and Recreation Nova Southeastern University Science and Education The Field Museum Department of Biology Boston University Wake Forest University Department of Geographical Sciences University of Maryland San Diego Zoo Institute for Conservation Research Biology Department Washington State University Yale School of Forestry & Environmental Studies Columbia University Department of Environmental Science Policy and Management University of California Berkeley School of Earth Sciences and Environmental Sustainability Northern Arizona University Department of Geography and the Environment University of Texas at Austin UNELLEZ-Guanare Programa de Ciencias del Agro y el Mar Herbario Universitario (PORT) Ci Progress GreenLife Universidad Nacional Experimental de Guayana Instituto Venezolano de Investigaciones Científicas (IVIC) Universidad de los Andes Viet Nature Conservation Centre CIRAD School of Life Sciences University of Lincoln UNESP - São Paulo State University Instituto de Biociências Universidade Estadual Paulista Gordon and Betty Moore Foundation: 1656 FAPESP: 2012/51509-8 FAPESP: 2012/51872-5 Fundação de Amparo à Pesquisa do Estado de Goiás: 2017/10267000329 European Research Council: 291585 Gordon and Betty Moore Foundation: 5349 European Research Council: 758873 Belgian Federal Science Policy Office: BR/132/A1/AFRIFORD Belgian Federal Science Policy Office: BR/143/A3/HERBAXYLAREDD Vlaamse Interuniversitaire Raad: CD2018TEA459A103 CNPq: CNPq/PPBio/457602/2012-0 National Science Foundation: DEB 1754647 Natural Environment Research Council: E/M0022021/1 Royal Society: ICA/R1/180100 Natural Environment Research Council: NE/D005590/1 European Research Council: NE/F005806/1 Natural Environment Research Council: NE/F005806/1 FAPESP: NE/K016431/1 Natural Environment Research Council: NE/N004655/1 FAPESP: NE/N012542/1 Royal Society: NE/P008755/1 FAPESP: NE/S011811/1 National Geographic Society: NE/T01279X/1 CNPq: PELD/441244/2016-5 Belgian Federal Science Policy Office: SD/AR/01A/COBIMFO

Objectives: To describe and compare patients appraisal of the rehabilitation and adherence to the rehabilitation program after acute ACL injury treated with (ACLR) or without (non-ACLR) reconstruction. Design: Prospective cohort study. Participants: 275 patients (143 females; mean age 25 +/- 7 years) with acute ACL injury, of whom 166 patients had ACLR within 24 months. Main outcome: Adherence to rehabilitation was assessed using the modified Sports Injury Rehabilitation Adherence Scale (SIRAS). Results: Appraisal of rehabilitation was higher in the post-ACLR group compared to the non-ACLR group at 3 months (91% compared to 70% scored rehabilitation as necessary, p = 0.025) and at 6 months (87% compared to 70% scored it as necessary, p = 0.017). SIRAS score did not differ between 3 and 6 months for the non-ACLR group (median (IQR) 13 (2) vs 13 (2)) or the post-ACLR group (14 (1) vs 14 (2), p>0.05). The post-ACLR group had a higher SIRAS score than the non-ACLR group at 3 and 6 months (p ≤0.001). Conclusion: Patients treated with ACLR reported valuing their rehabilitation more and rated greater adherence to the rehabilitation programme than non-surgically treated patients. As rehabilitation is essential for good knee function, strategies to improve adherence after non-ACLR treatment should be implemented. Funding Agencies: Swedish Medical Research Council (SMRC)European Commission [VR 2015-03687, VR 2018-02563]; Swedish Research Council for Sport Science (CIF) [P2017-0151, P2018-0132, P2019-0071]; Medical Research Council of Southeast Sweden, UK Research & Innovation (UKRI)Medical Research Council UK (MRC) [FORSS 662081]; ALF Grants Region Östergotland [LIO-798907, 900721, 934538]

Findings 5585 families with Lynch syndrome from 22 countries were eligible for the analysis. Of these, there were insufficient numbers to estimate penetrance for Asia and South America, and for those with EPCAM variants. Therefore, we used data (collected between July 11, 2014, and Dec 31, 2018) from 5255 families (1829 MLH1, 2179 MSH2, 798 MSH6, and 449 PMS2), comprising 79 809 relatives, recruited in 15 countries in North America, Europe, and Australasia. There was strong evidence of the existence of unknown familial risk factors modifying colorectal cancer risk for Lynch syndrome carriers (p 0 center dot 0001 for each of the three three continents). These familial risk factors resulted in a wide within-gene variation in the risk of colorectal cancer for men and women from each continent who all carried pathogenic variants in the same gene or the MSH2 c.942+3A T variant. The variation was especially prominent for MLH1 and MSH2 variant carriers, depending on gene, sex and continent, with 7-56% of carriers having a colorectal cancer penetrance of less than 20%, 9-44% having a penetrance of more than 80%, and onlyBackground Existing clinical practice guidelines for carriers of pathogenic variants of DNA mismatch repair genes (Lynch syndrome) are based on the mean age-specific cumulative risk (penetrance) of colorectal cancer for all carriers of pathogenic variants in the same gene. We aimed to estimate the variation in the penetrance of colorectal cancer between carriers of pathogenic variants in the same gene by sex and continent of residence. Methods In this retrospective cohort study, we sourced data from the International Mismatch Repair Consortium, which comprises 273 members from 122 research centres or clinics in 32 countries from six continents who are involved in Lynch syndrome research. Families with at least three members and at least one confirmed carrier of a pathogenic or likely pathogenic variant in a DNA mismatch repair gene (MLH1, MSH2, MSH6, or PMS2) were included. The families of probands with known de-novo pathogenic variants were excluded. Data were collected on the method of ascertainment of the family, sex, carrier status, cancer diagnoses, and ages at the time of pedigree collection and at last contact or death. We used a segregation analysis conditioned on ascertainment to estimate the mean penetrance of colorectal cancer and modelled unmeasured polygenic factors to estimate the variation in penetrance. The existence of unknown familial risk factors modifying colorectal cancer risk for Lynch syndrome carriers was tested by use of a Wald p value for the null hypothesis that the polygenic SD is zero. Findings 5585 families with Lynch syndrome from 22 countries were eligible for the analysis. Of these, there were insufficient numbers to estimate penetrance for Asia and South America, and for those with EPCAM variants. Therefore, we used data (collected between July 11, 2014, and Dec 31, 2018) from 5255 families (1829 MLH1, 2179 MSH2, 798 MSH6, and 449 PMS2), comprising 79 809 relatives, recruited in 15 countries in North America, Europe, and Australasia. There was strong evidence of the existence of unknown familial risk factors modifying colorectal cancer risk for Lynch syndrome carriers (pT variant. The variation was especially prominent for MLH1 and MSH2 variant carriers, depending on gene, sex and continent, with 7-56% of carriers having a colorectal cancer penetrance of less than 20%, 9-44% having a penetrance of more than 80%, and only 10-19% having a penetrance of 40-60%. Interpretation Our study findings highlight the important role of risk modifiers, which could lead to personalised risk assessments for precision prevention and early detection of colorectal cancer for people with Lynch syndrome. Funding National Health and Medical Research Council, Australia. Copyright (c) 2021 Elsevier Ltd. All rights reserved.Methods In this retrospective cohort study, we sourced data from the International Mismatch Repair Consortium, which comprises 273 members from 122 research centres or clinics in 32 countries from six continents who are involved in Lynch syndrome research. Families with at least three members and at least one confirmed carrier of a pathogenic or likely pathogenic variant in a DNA mismatch repair gene (MLH1, MSH2, MSH6, or PMS2) were included. The families of probands with known de-novo pathogenic variants were excluded. Data were collected on the method of ascertainment of the family, sex, carrier status, cancer diagnoses, and ages at the time of pedigree collection and at last contact or death. We used a segregation analysis conditioned on ascertainment to estimate the mean penetrance of colorectal cancer and modelled unmeasured polygenic factors to estimate the variation in penetrance. The existence of unknown familial risk factors modifying colorectal cancer risk for Lynch syndrome carriers was tested by use of a Wald p value for the null hypothesis that the polygenic SD is zero.

AIMS AND OBJECTIVES To describe how nurses and nurse managers consider sustainable development principles in their daily work, how well they recognise these principles and how these principles are considered in decision-making in perioperative work. BACKGROUND Sustainable development involves interpersonal social and cultural relations and long-term economic and ecological thinking in societal decision-making. These dimensions are well-suited for a foundation of decision-making in acute health care. No previous research has been performed on perioperative work from the sustainable development perspective. DESIGN Qualitative descriptive design was used. Data were collected from perioperative nurses (n = 20) and nurse managers (n = 6) working in five surgical departments in a Finnish university hospital. Data were analysed by content analysis. The reporting follows qualitative research checklist (COREQ). RESULTS The principles of sustainable development were poorly known among the participants. Nurse managers considered their opportunities to influence decision-making were reduced by their limited economic knowledge. Resource use, individuality, and ecological viewpoints were emphasised in the decision-making process in perioperative work. CONCLUSIONS Findings reveal that perioperative nurses and nurse managers are aware of economic and ecological sustainability, but they do not actively consider it as part of their work. Social and cultural sustainability must be developed further in decision-making in perioperative work. RELEVANCE TO CLINICAL PRACTICE Perioperative nurses and nurse managers consider that it is important to develop the principles of sustainable development in perioperative work. This research indicates that economic understanding is not guiding decision-making, and there is a lack of knowledge about the benefits of ecological procedures. Social and cultural sustainability are not connected in perioperative work, although there is collaboration between the surgical team and the patient is essential. This study helps to organise operating room management effectively and diversely.

Objectives: To assess the implementation, limited efficacy, and acceptability of the BEAST (better and safer return to sport) tool a rehabilitation and return-to-sport (RTS) decision tool after anterior cruciate ligament reconstruction (ACLR) in nonprofessional athletes. Design: Prospective cohort. Participants: 43 nonprofessional pivoting sport athletes with ACLR. Main outcome: Clinician-and athlete-experienced implementation challenges (implementation), changes in quadriceps power, side hop and triple hop performance from 6 to 8 months after ACLR (limited efficacy), athletes beliefs about the individual rehabilitation and RTS plans produced by the BEAST tool (acceptability). Results: The BEAST tool was developed and then implemented as planned for 39/43 (91%) athletes. Hop and quadriceps power performance improved significantly, with the largest improvement in involved quadriceps power (standardised response mean 1.4, 95% CI:1.1-1.8). Athletes believed the rehabilitation and RTS plan would facilitate RTS (8.2 [SD: 2.0]) and reduce injury risk (8.3 [SD: 1.2]; 0 = not likely at all, 10 = extremely likely). Conclusion: The BEAST tool was implemented with few challenges and adjustments were rarely necessary. Athletes had large improvements in quadriceps power and hop performance on the involved leg. Athletes believed that the individual rehabilitation and RTS plans produced by the tool would facilitate RTS and reduce injury risk. (c) 2021 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). Funding Agencies|Swedish Research Council for Sport Science; International Olympic Committee; Norwegian Fund for Post-Graduate Training in Physiotherapy

Purpose To investigate among women ≥ 70 years with early stage invasive breast cancer, whether primary endocrine therapy and omission of surgery resulted in an inferior relative survival, whether the omission of preoperative imaging resulted in an inferior local control, and whether the omission of axillary staging resulted in an inferior regional control and inferior relative survival. Methods A single center retrospective cohort study at Herlev Hospital, Denmark. Relative survival was expressed as standardized mortality ratios (SMR) and differences were estimated using Poisson regression and evaluated by rate ratios (RR). Differences in local and in regional recurrence were estimated by a Cause Specific Hazard Model and evaluated by hazard ratios (HR). Models were adjusted for age, comorbidity, and tumor size. Results We identified 1,142 women. Patients who received only endocrine therapy had a higher SMR than patients treated with primary surgery (RR = 2.57;95%CI:2.01–3.30). Patients treated with primary breast conserving surgery (BCS) did not have a lower risk of local recurrence if they received preoperative imaging (HR = 0.88;95%CI:0.27–2.81). Finally, patients who received an axillary staging had a lower risk of regional recurrence compared to patients who did not receive axillary surgery (HR = 0.25;95%CI:0.08–0.84), but not a statistically significant superior relative survival (RR = 0.78;95%CI:0.60-1.00). Conclusion Elderly women with early stage breast cancer treated with only endocrine therapy had an inferior relative survival, omission of axillary staging resulted in a higher risk of regional recurrence and a tendency to an inferior relative survival, and omission of preoperative imaging before BCS did not result in a higher risk of local recurrence.

Aims: Improvements in technology and access have led to growing adoption of continuous glucose monitoring (CGM). Targets for glucose metrics including time in range (TIR) have been published. We aimed to investigate i) the proportion of people with ≥70% TIR and ii) the proportion with ≥70% TIR and Methods: Data were collected from 2015 to 2019 from the Cornerstone4Care (C4C) database, a freely available patient support program for people with both type 1 diabetes (T1D) and type 2 diabetes (T2D) on any treatment type. CGM traces were divided into 14-day periods according to the ambulatory glucose profile (AGP)-reporting system. Only profiles with data aligned with these standards were included. Patient data are presented using the first or the mean of all AGP profiles. Results: In total, 484 persons uploaded CGM-data to the database (4727 AGPs); 242 had T1D and 74 had T2D (self-reported), the rest were unknown (Table). People uploaded between 1 and 75 AGPs (mean=10). Average TIR (70-180 mg/dL) based on mean profiles was 63%, 68% and 64% for T1D, T2D and all, respectively. Conclusions: Less than half of the population achieved ≥70% TIR, ~30% with ≥70% TIR and Disclosure R. M. Bergenstal: Advisory Panel; Self; Abbott Diabetes, Eli Lilly and Company, Novo Nordisk, Onduo LLC., Roche, Sanofi, United Healthcare, Consultant; Self; Abbott Diabetes, Ascensia, Dexcom, Inc., Eli Lilly and Company, Hygieia, Johnson & Johnson, Medtronic, Novo Nordisk, Onduo LLC., Roche, Sanofi, United Healthcare, Other Relationship; Self; HealthPartners Institute, Research Support; Self; Abbott Diabetes, Dexcom, Inc., Eli Lilly and Company, Helmsley Charitable Trust, Hygieia, Johnson & Johnson, Medtronic, NIDDK, Novo Nordisk, Onduo LLC., Roche, Sanofi, United Healthcare. E. Hachmann-nielsen: Employee; Self; Novo Nordisk A/S. J. Tarp: Employee; Self; Novo Nordisk. K. Kvist: Employee; Self; Novo Nordisk A/S. J. B. Buse: Consultant; Self; Cirius Therapeutics, CSL Behring, Fortress Biotch, Mellitus Health, Moderna, Pendulum Therapeutics, Praetego Inc., Stability Health, Zealand Pharma A/S, Other Relationship; Self; AstraZeneca, Eli Lilly and Company, Novo Nordisk, vTv Therapeutics, Research Support; Self; NovaTarg Therapeutics, Novo Nordisk, Sanofi, Tolerion, Inc., vTv Therapeutics, Stock/Shareholder; Self; Mellitus Health, Pendulum Therapeutics, PhaseBio Pharmaceuticals, Inc., Stability Health. Funding Novo Nordisk A/S

Research question What is the risk of miscarriage after a viable fetus verified on ultrasound at 6–8 weeks’ gestation among women who conceive with medically assisted reproduction (MAR), stratified by type of fertility treatment? Design A nationwide register-based cohort study of women identified in the Danish ART-Registry with a viable singleton pregnancy at 6–8 weeks’ gestation between 2007 and 2010 (n = 10,011). Women were identified from The Danish Fetal Medicine Database (DFMD), which holds information on early (between 6–8 and 11–14 weeks) and late (between 11–14 and 22 weeks) miscarriages. The late miscarriage rate was compared with a control group of naturally conceived pregnancies with a viable fetus at 11–14 weeks’ gestation from 2008 to 2010, identified in the DFMD (n = 146,932). Results In the MAR1 cohort, the overall miscarriage rate was 11.8% (1091/9261) after an ultrasound verified viable pregnancy at 6–8 weeks’ gestation. Most miscarriages occurred before the 11–14-week scan (1035/1091 [94.9%]). The early miscarriage rate was slightly higher in women who conceived with frozen embryo transfer compared with intrauterine insemination (IUI), corresponding to an adjusted OR of 1.31 (1.02 to 1.68). We found no significant risk associated with IVF and intracytoplasmic sperm injection compared with IUI pregnancies. The late miscarriage rate was 0.8% in women conceiving with MAR and 0.6% among controls (P = 0.013). Conclusions After adjustment for maternal characteristics, none of the fertility treatment types were associated with an increased risk of miscarriage compared with naturally conceiving women.

Identifying risk factors for major depression and depressive symptoms in youths could have important implications for prevention efforts. This study examined the association of polygenic risk scores (PRSs) for a broad depression phenotype derived from a large-scale genome-wide association study (GWAS) in adults, and its interaction with childhood abuse, with clinically relevant depression outcomes in clinical and epidemiological youth cohorts.The clinical cohort comprised 279 youths with major depression (mean age=14.76 years [SD=2.00], 68% female) and 187 healthy control subjects (mean age=14.67 years [SD=2.45], 63% female). The first epidemiological cohort included 1,450 youths (mean age=13.99 years [SD=0.92], 63% female). Of those, 694 who were not clinically depressed at baseline underwent follow-ups at 6, 12, and 24 months. The replication epidemiological cohort comprised children assessed at ages 8 (N=184; 49.2% female) and 11 (N=317; 46.7% female) years. All cohorts were genome-wide genotyped and completed measures for major depression, depressive symptoms, and/or childhood abuse. Summary statistics from the largest GWAS to date on depression were used to calculate the depression PRS.In the clinical cohort, the depression PRS predicted case-control status (odds ratio=1.560, 95% CI=1.230-1.980), depression severity (β=0.177, SE=0.069), and age at onset (β=-0.375, SE=0.160). In the first epidemiological cohort, the depression PRS predicted baseline depressive symptoms (β=0.557, SE=0.200) and prospectively predicted onset of moderate to severe depressive symptoms (hazard ratio=1.202, 95% CI=1.045-1.383). The associations with depressive symptoms were replicated in the second epidemiological cohort. Evidence was found for an additive, but not an interactive, effect of the depression PRS and childhood abuse on depression outcomes.Depression PRSs derived from adults generalize to depression outcomes in youths and may serve as an early indicator of clinically significant levels of depression.