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IntroductionIt would be valuable if home-based rehabilitation training technologies could automatically assess arm impairment after stroke. Here, we tested whether a simple measure—the repetition rate (or “rep rate”) when performing specific exercises as measured with simple sensors—can be used to estimate Upper Extremity Fugl-Meyer (UEFM) score.Methods41 individuals with arm impairment after stroke performed 12 sensor-guided exercises under therapist supervision using a commercial sensor system comprised of two pucks that use force and motion sensing to measure the start and end of each exercise repetition. 14 of these participants then used the system at home for three weeks.ResultsUsing linear regression, UEFM score was well estimated using the rep rate of one forward-reaching exercise from the set of 12 exercises (r2 = 0.75); this exercise required participants to alternately tap pucks spaced about 20 cm apart (one proximal, one distal) on a table in front of them. UEFM score was even better predicted using an exponential model and forward-reaching rep rate (Leave One Out Cross Validation (LOOCV) r2 = 0.83). We also tested the ability of a nonlinear, multivariate model (a regression tree) to predict UEFM, but such a model did not improve prediction (LOOCV r2 = 0.72). However, the optimal decision tree also used the forward-reaching task along with a pinch grip task to subdivide more and less impaired patients in a way consistent with clinical intuition. At home, rep rate for the forward-reaching exercise well predicted UEFM score using an exponential model (LOOCV r2 = 0.69), but only after we re-estimated coefficients using the home data.DiscussionThese results show how a simple measure—exercise rep rate measured with simple sensors—can be used to infer an arm impairment score and suggest that prediction models should be tuned separately for the clinic and home environments.

IntroductionChronic pelvic pain (CPP) is a common condition affecting up to 26.6% of women, with many suffering for several years before diagnosis and/or treatment. Its clinical presentation is varied and there are frequently comorbid conditions both within and outside the pelvis. We aim to explore whether specific subgroups of women with CPP report different clinical symptoms and differing impact of pain on their quality of life (QoL).MethodsThe study is part of the Translational Research in Pelvic Pain (TRiPP) project which is a cross-sectional observational cohort study. The study includes 769 female participants of reproductive age who completed an extensive set of questions derived from standardised WERF EPHect questionnaires. Within this population we defined a control group (reporting no pelvic pain, no bladder pain syndrome, and no endometriosis diagnosis, N = 230) and four pain groups: endometriosis-associated pain (EAP, N = 237), interstitial cystitis/bladder pain syndrome (BPS, N = 72), comorbid endometriosis-associated pain and BPS (EABP, N = 120), and pelvic pain only (PP, N = 127).ResultsClinical profiles of women with CPP (13–50 years old) show variability of clinical symptoms. The EAP and EABP groups scored higher than the PP group (p

Although varicose veins are a common condition, the genetic basis is not well understood. Here, the authors find genetic variants associated with varicose veins and show that a higher polygenic risk score for varicose veins correlates with a greater likelihood of patients undergoing surgical treatment.

Arm movement recovery after stroke can improve with sufficient exercise. However, rehabilitation therapy sessions are typically not enough. To address the need for effective methods of increasing arm exercise outside therapy sessions we developed a novel armrest, called Boost. It easily attaches to a standard manual wheelchair just like a conventional armrest and enables users to exercise their arm in a linear forward-back motion. This paper provides a detailed design description of Boost, the biomechanical analysis method to evaluate the joint torques required to operate it, and the results of pilot testing with five stroke patients. Biomechanics results show the required shoulder flexion and elbow extension torques range from −25% to +36% of the torques required to propel a standard pushrim wheelchair, depending on the direction of applied force. In pilot testing, all five participants were able to exercise the arm with Boost in stationary mode (with lower physical demand). Three achieved overground ambulation (with higher physical demand) exceeding 2 m/s after 2–5 practice trials; two of these could not propel their wheelchair with the pushrim. This simple to use, dynamic armrest provides people with hemiparesis a way to access repetitive arm exercise outside of therapy sessions, independently right in their wheelchair. Significantly, Boost removes the requirements to reach, grip, and release the pushrim to propel a wheelchair, an action many individuals with stroke cannot complete.

Purpose: To examine the current provision and practice patterns of diabetic retinopathy screening (DRS) in Haryana. Methods: This was a descriptive cross-sectional survey in Haryana. All ophthalmologists registered with Haryana Ophthalmological Society in Haryana state were invited to participate on an online survey comprised of twenty questions exploring diabetic retinopathy screening provision, and barriers to screening services in Haryana. Results: The response rate was 82% (153/186). The majority (84%) of the eye care providers practiced in urban areas. Most ophthalmologists (89%, 136/153), considered diabetic retinopathy screening by non-ophthalmic human resource inappropriate because of technical feasibility issues (62%) followed by non-availability of trained staff (33%). Only half (54%) of the respondents had access to written protocols for the diagnosis and management of diabetic retinopathy in their practice. Barriers to optimize diabetic retinopathy screening were lack of knowledge or awareness among patients (95.5%), perception that eye complications were unlikely (76%) and cost of care (30%). Conclusion: Diabetic retinopathy screening practices are mainly opportunistic and urban-centric, likely delivering inequitable services for the rural populations in the state. The inclusion of other personnel in screening will require stakeholder engagement from all health professions and changing the perceptions of ophthalmologists about task shifting.

IntroductionCaesarean section (C-section) is a life-saving procedure when medically indicated but unmet need and overuse can add to avoidable morbidity and mortality. It is not clear whether C-section has a negative impact on breastfeeding and there is limited data available on rates of C-section or breastfeeding from Northern Cyprus, an emerging region in Europe. This study aimed to investigate prevalence, trends and associations of C-section and breastfeeding in this population.MethodsUsing self-reported data from the representative Cyprus Women's Health Research (COHERE) Initiative, we used 2,836 first pregnancies to describe trends in C-section and breastfeeding between 1981 and 2017. Using modified Poisson regression, we examined the relationship between year of pregnancy and C-section and breastfeeding, as well as the association between C-section and breastfeeding prevalence and duration.ResultsC-section prevalence in first pregnancies increased from 11.1% in 1981 to 72.5% in 2017 with a relative risk of 2.60 (95%CI; 2.14-2.15) of babies being delivered by C-section after 2005 compared to before 1995, after full adjustment for demographic and maternal medical and pregnancy related factors. Prevalence of ever breastfeeding remained steady throughout the years at 88.7% and there was no significant association between breastfeeding initiation and the year of pregnancy, or demographic and maternal medical and pregnancy related variables. After full adjustment, women who gave birth after 2005 were 1.24 (95%CI; 1.06-1.45) times more likely to breastfeed for >12 weeks compared to women who gave birth before 1995. There was no association between C-section and breastfeeding prevalence or length.ConclusionPrevalence of C-section in this population is much higher than WHO recommendations. Public awareness campaigns surrounding choice during pregnancy and change in legal framework to allow for midwife-led continuity models of birthing care should be implemented. Further research is required to understand the reasons and drivers behind this high rate.

Abstract Background Insomnia is common in people with long-term medical conditions and is related to increased mortality and morbidity. Cognitive behavioral therapy for insomnia (CBT-I) is first choice treatment and effective for people with insomnia and comorbid long-term medical conditions. However, CBT-I has some limitations as it might not always be available or appeal to patients with medical conditions. Furthermore, a small proportion of patients do not respond to CBT-I. Preliminary evidence and clinical experience suggest that low-dose amitriptyline (AM) might be an effective alternative to treat insomnia in patients with medical comorbidity. In this randomized controlled trial, we will determine whether AM is non-inferior to the first choice treatment for insomnia, CBT-I. Methods/design This study will test if treatment with low-dose amitriptyline for insomnia in patients with medical comorbidity is non-inferior to CBT-I in a multicenter randomized controlled non-inferiority trial. Participants will be 190 adults with a long-term medical condition and insomnia. Participants will be randomly allocated to one of two intervention arms: 12 weeks AM (starting with 10 mg per day, and if ineffective at 3 weeks, doubling this dose) or 12 weeks of CBT-I consisting of 6 weekly sessions and a follow-up session 6 weeks later. The primary outcome is subjective insomnia severity, measured with the Insomnia Severity Index (ISI). The primary endpoint is at 12 weeks. Secondary outcomes include sleep quality (e.g., sleep efficiency), questionnaires on daytime functioning (physical functioning and impairment of functioning), and symptoms (e.g., fatigue, pain, anxiety) at 12 weeks and 12 months post treatment and relapse of insomnia until 12 months after treatment. Discussion Irrespective of the outcome, this study will be a much-needed contribution to evidence based clinical guidelines on the treatment of insomnia in patients with medical comorbidity. Trial registration Dutch Trial Register NTR NL7971 . Registered on 18 August 2019

Background: The burden of urological diseases is rising as the worldwide population ages. Although specialist urological provision is needed, a large proportion of these conditions will be managed in primary care. The importance of including urology in medical education currently remains unclear. Objective: To provide recommendations on undergraduate medical education for urology in Europe. Design, setting, and participants: A three-round Delphi process to reach consensus on standardising the undergraduate urology curriculum in Europe was endorsed by the European School of Urology. Outcome measurements and statistical analysis: The levels of agreement were set using a nine-point scale according to the GRADE grid: 1–3, disagree; 4–6, uncertain; and 7–9, agree. Consensus was defined as at least 70% of the participants scoring within the same 3-point grouping. Results and limitations: Overall, consensus was reached for 20 of 34 statements (70.5%) across the three Delphi rounds, with agreement for 75% (n = 15) and disagreement for 25% (n = 5). The following main points were agreed. Urological teaching should be introduced before year 5 of medical school, with at least 20 h of theoretical activities and at least 30 h of practical activities. Urology should be taught as a stand-alone subject rather than combined with another surgical specialty or a nephrology programme. The participants agreed that urology should be taught according to symptoms. A urology programme should include the anatomy and physiology of the urinary tract, and students should know how to clinically assess a urological patient. Conclusions: Our recommended urology pathway will allow European medical schools to provide a more comprehensive undergraduate urology curriculum. It will also help to improve and maintain standards of urology undergraduate teaching across Europe. Patient summary: Our survey showed that urology in universities should have, at minimum, time for theoretical and practical activities and should be taught as a stand-alone subject on the basis of symptoms. Students should give feedback to facilitate constant improvement and evolution of the teaching programme.

Each of us should work to save the planet from the impending ecological disaster to the best of our abilities. As chemical engineering educators, this means recruiting the young people in our care to apply their skills to the same endeavour. This contribution presents two examples of activities currently in progress at the Technion, Israel and at the University of Twente, Holland, to achieve this aim. The first example concerns the setup of a fast moving consumer goods supply chain, balancing profit with environmental impact. The second example concerns the sustainable production of methanol from concentrated carbon dioxide streams and renewable hydrogen. These two examples illustrate how students can be motivated to design emission-free processes and are intended to feed a further discussion how sustainability can be structurally integrated in the chemical engineering curriculum. Emission-free, sustainability, chemical engineering curriculum, education.

PURPOSE:Ablation plays a growing role in the treatment of small renal masses (SRMs) due to its nephron sparing properties and low invasiveness. Irreversible electroporation (IRE) has the potential, although still experimental, to overcome current limitations of thermal ablation. No prospective imaging studies exist of the ablation zone in the follow up after renal IRE in humans. Objectives are to assess computed tomography (CT) and magnetic resonance imaging (MRI) on the ablation zone volume (AZV), enhancement and imaging characteristics after renal IRE.METHODS:Prospective phase 2 study of IRE in nine patients with ten SRMs. MRI imaging was performed pre-IRE, 1 week, 3 months, 6 months and 12 months after IRE. CT was performed pre-IRE, perioperatively (direct after ablation), 3 months, 6 months and 12 months after IRE. AZVs were assessed by two independent observers. Observer variation was analyzed. Evolution of AZVs, and relation between the needle configuration volume (NCV; planned AZV) and CT- and MRI volumes were evaluated.RESULTS:Eight SRMs were clear cell renal cell carcinomas, one SRM was a papillary renal cell carcinoma and one patient had a non-diagnostic biopsy. On CT, median AZV increased perioperatively until 3 months post-IRE (respectively, 16.8 cm3 and 6.2 cm3) compared to the NCV (4.8 cm3). On MRI, median AZV increased 1-week post-IRE until 3 months post-IRE (respectively, 14.5 cm3 and 4.6 cm3) compared to the NCV (4.8 cm3). At 6 months the AZV starts decreasing (CT 4.8 cm3; MRI 3.0 cm3), continuing at 12 months (CT 4.2 cm3, MRI 1.1 cm3). Strong correlation was demonstrated between the planning and the post-treatment volumes. Inter-observer agreement between observers was excellent (CT 95% CI 0.82-0.95, MRI 95% CI 0.86-0.96). All SRMs appeared non-enhanced immediately after ablation, except for one residual tumour. Subtraction images confirmed non-enhancement on MRI in unclear enhancement cases (3/9). Directly after IRE, gas bubbles, perinephric stranding and edema were observed in all cases.CONCLUSION:The AZV increases immediately on CT until 3 months after IRE. On MRI, the AZV increases at 1 week until 3 months post-IRE. At 6 months the AZV starts decreasing until 12 months post-IRE on both CT and MRI. Enhancement was absent post-IRE, except for one residual tumour. Gas bubbles, perinephric stranding and edema are normal findings directly post-IRE.

Many people with a stroke have a severely paretic arm, and it is often assumed that they are unable to learn novel, skilled behaviors that incorporate use of that arm. Here, we show that a group of people with chronic stroke (n = 5, upper extremity Fugl-Meyer scores: 31, 30, 26, 22, 8) learned to use their impaired arm to propel a novel, yoked-clutch lever drive wheelchair. Over six daily training sessions, each involving about 134 training movements with their "useless" arm, the users gradually achieved a 3-fold increase in wheelchair speed on average, with a 4-6 fold increase for three of the participants. They did this by learning a bimanual skill: pushing the levers with both arms while activating the yoked-clutches at the right time with their ipsilesional (i.e. "good") hand to propel the wheelchair forward. They perceived the task as highly motivating and useful. The speed improvements exceeded a 1.5-factor improvement observed when young, unimpaired users learned to propel the chair. The learning rate also exceeded a sample of learning rates from a variety of classic learning studies. These results suggest that appropriately-designed assistive technologies (or "unmasking technologies - UTs") can unleash a powerful, latent ability for motor learning even for severely paretic arms. While UTs may not reduce clinical impairment, they may facilitate large improvements in a specific functional ability.

Endometriosis is a heritable hormone-dependent gynecological disorder, associated with severe pelvic pain and reduced fertility; however, its molecular mechanisms remain largely unknown. Here we perform a meta-analysis of 11 genome-wide association case-control data sets, totalling 17,045 endometriosis cases and 191,596 controls. In addition to replicating previously reported loci, we identify five novel loci significantly associated with endometriosis risk (P

ImportanceThe causal direction and magnitude of the association between telomere length and incidence of cancer and non-neoplastic diseases is uncertain owing to the susceptibility of observational studies to confounding and reverse causation.ObjectiveTo conduct a Mendelian randomization study, using germline genetic variants as instrumental variables, to appraise the causal relevance of telomere length for risk of cancer and non-neoplastic diseases.Data sourcesGenomewide association studies (GWAS) published up to January 15, 2015.Study selectionGWAS of noncommunicable diseases that assayed germline genetic variation and did not select cohort or control participants on the basis of preexisting diseases. Of 163 GWAS of noncommunicable diseases identified, summary data from 103 were available.Data extraction and synthesisSummary association statistics for single nucleotide polymorphisms (SNPs) that are strongly associated with telomere length in the general population.Main outcomes and measuresOdds ratios (ORs) and 95% confidence intervals (CIs) for disease per standard deviation (SD) higher telomere length due to germline genetic variation.ResultsSummary data were available for 35 cancers and 48 non-neoplastic diseases, corresponding to 420 081 cases (median cases, 2526 per disease) and 1 093 105 controls (median, 6789 per disease). Increased telomere length due to germline genetic variation was generally associated with increased risk for site-specific cancers. The strongest associations (ORs [95% CIs] per 1-SD change in genetically increased telomere length) were observed for glioma, 5.27 (3.15-8.81); serous low-malignant-potential ovarian cancer, 4.35 (2.39-7.94); lung adenocarcinoma, 3.19 (2.40-4.22); neuroblastoma, 2.98 (1.92-4.62); bladder cancer, 2.19 (1.32-3.66); melanoma, 1.87 (1.55-2.26); testicular cancer, 1.76 (1.02-3.04); kidney cancer, 1.55 (1.08-2.23); and endometrial cancer, 1.31 (1.07-1.61). Associations were stronger for rarer cancers and at tissue sites with lower rates of stem cell division. There was generally little evidence of association between genetically increased telomere length and risk of psychiatric, autoimmune, inflammatory, diabetic, and other non-neoplastic diseases, except for coronary heart disease (OR, 0.78 [95% CI, 0.67-0.90]), abdominal aortic aneurysm (OR, 0.63 [95% CI, 0.49-0.81]), celiac disease (OR, 0.42 [95% CI, 0.28-0.61]) and interstitial lung disease (OR, 0.09 [95% CI, 0.05-0.15]).Conclusions and relevanceIt is likely that longer telomeres increase risk for several cancers but reduce risk for some non-neoplastic diseases, including cardiovascular diseases.

ImportanceThe causal direction and magnitude of the association between telomere length and incidence of cancer and non-neoplastic diseases is uncertain owing to the susceptibility of observational studies to confounding and reverse causation.ObjectiveTo conduct a Mendelian randomization study, using germline genetic variants as instrumental variables, to appraise the causal relevance of telomere length for risk of cancer and non-neoplastic diseases.Data sourcesGenomewide association studies (GWAS) published up to January 15, 2015.Study selectionGWAS of noncommunicable diseases that assayed germline genetic variation and did not select cohort or control participants on the basis of preexisting diseases. Of 163 GWAS of noncommunicable diseases identified, summary data from 103 were available.Data extraction and synthesisSummary association statistics for single nucleotide polymorphisms (SNPs) that are strongly associated with telomere length in the general population.Main outcomes and measuresOdds ratios (ORs) and 95% confidence intervals (CIs) for disease per standard deviation (SD) higher telomere length due to germline genetic variation.ResultsSummary data were available for 35 cancers and 48 non-neoplastic diseases, corresponding to 420 081 cases (median cases, 2526 per disease) and 1 093 105 controls (median, 6789 per disease). Increased telomere length due to germline genetic variation was generally associated with increased risk for site-specific cancers. The strongest associations (ORs [95% CIs] per 1-SD change in genetically increased telomere length) were observed for glioma, 5.27 (3.15-8.81); serous low-malignant-potential ovarian cancer, 4.35 (2.39-7.94); lung adenocarcinoma, 3.19 (2.40-4.22); neuroblastoma, 2.98 (1.92-4.62); bladder cancer, 2.19 (1.32-3.66); melanoma, 1.87 (1.55-2.26); testicular cancer, 1.76 (1.02-3.04); kidney cancer, 1.55 (1.08-2.23); and endometrial cancer, 1.31 (1.07-1.61). Associations were stronger for rarer cancers and at tissue sites with lower rates of stem cell division. There was generally little evidence of association between genetically increased telomere length and risk of psychiatric, autoimmune, inflammatory, diabetic, and other non-neoplastic diseases, except for coronary heart disease (OR, 0.78 [95% CI, 0.67-0.90]), abdominal aortic aneurysm (OR, 0.63 [95% CI, 0.49-0.81]), celiac disease (OR, 0.42 [95% CI, 0.28-0.61]) and interstitial lung disease (OR, 0.09 [95% CI, 0.05-0.15]).Conclusions and relevanceIt is likely that longer telomeres increase risk for several cancers but reduce risk for some non-neoplastic diseases, including cardiovascular diseases.

The 3rd International Consensus Workshop on Research Priorities in Endometriosis was held in São Paulo on May 4, 2014, following the 12th World Congress on Endometriosis. The workshop was attended by 60 participants from 19 countries and was divided into 5 main sessions covering pathogenesis/pathophysiology, symptoms, diagnosis/classification/prognosis, disease/symptom management, and research policy. This research priorities consensus statement builds on earlier efforts to develop research directions for endometriosis. Of the 56 research recommendations from the 2011 meeting in Montpellier, a total of 41 remained unchanged, 13 were updated, and 2 were deemed to be completed. Fifty-three new research recommendations were made at the 2014 meeting in Sao Paulo, which in addition to the 13 updated recommendations resulted in a total of 66 new recommendations for research. The research recommendations published herein, as well as those from the 2 previous papers from international consensus workshops, are an attempt to promote high-quality research in endometriosis by identifying and agreeing on key issues that require investigation. New areas included in the 2014 recommendations include infertility, patient stratification, and research in emerging nations, in addition to an increased focus on translational research. A revised and updated set of research priorities that builds on this document will be developed at the 13th World Congress on Endometriosis to be held on May 17-20, 2017, in Vancouver, British Columbia, Canada.

Direct air carbon capture (DAC) technologies can substantially lower the CO2 concentrations in the atmosphere by enabling negative emissions. This study shows in detail the design of the DAC plant at industrial scale and provides insights on its performance in terms of process economic and CO2 emissions count. The proposed DAC plant is optimized to capture CO2 directly from the atmospheric air, employing a sensitivity analysis to find the influence of operation and design parameters on the total cost. Absorption using sodium hydroxide as chemisorbent is utilized with a capture rate of 0.7. Industrially mature common process units are considered to achieve a design that is relevant in the near future. An initial base case design indicates a carbon cost of 244 $/ton-CO2 with the operating expenses comprising 84% of the total cost. Then, two scenarios are proposed to enhance the process performance: heat integration and use of renewable energy. Through the heat integration, the carbon ratio (CO2 captured / CO2 emitted) improves from a value of 2.7 for the base case to 3.73, meaning less CO2 is emitted per captured amount due to lower fuel consumption. The resulting cost goes down to 125 $/ton-CO2, with two additional heat exchangers added to the network. Furthermore, renewable scenario is considered where a parallel electrolysis stage feeds the process hydrogen fuel and oxygen required for combustion in the calciner. This scenario indicates that higher operating costs are incurred due to the expensive green fuel. Finally, a profitability analysis is performed to establish the feasibility for further processing to methanol in a Power-to-X facility. The estimations indicate that the hydrogen price has to go down by 46.3% in order to break-even.

[This corrects the article DOI: 10.1371/journal.pmed.1003679.].

Abstract Background Staphylococcus and Streptococcus species can cause many different diseases, ranging from mild skin infections to life-threatening necrotizing fasciitis. Both genera consist of commensal species that colonize the skin and nose of humans and animals, and of which some can display a pathogenic phenotype. Results We compared 235 Staphylococcus and 315 Streptococcus genomes based on their protein domain content. We show the relationships between protein persistence and essentiality by integrating essentiality predictions from two metabolic models and essentiality measurements from six large-scale transposon mutagenesis experiments. We identified clusters of strains within species based on proteins associated to similar biological processes. We built Random Forest classifiers that predicted the zoonotic potential. Furthermore, we identified shared attributes between of Staphylococcus aureus and Streptococcus pyogenes that allow them to cause necrotizing fasciitis. Conclusions Differences observed in clustering of strains based on functional groups of proteins correlate with phenotypes such as host tropism, capability to infect multiple hosts and drug resistance. Our method provides a solid basis towards large-scale prediction of phenotypes based on genomic information.

The challenges associated with biofuel quality come from its heterogenous nature as biomass crops grow in different lands and under different conditions. Moreover, the inconsistency of the handling and sampling techniques in the laboratories or in the feedstock storage piles increase biomass variability. These issues affect the calorific value and as a result, the accuracy of the measurement for each feedstock pile of the measured data might be widely scattered. Furthermore, the current standards, e.g., ISO, DIN or ASTM are limited and do not consider the deviations caused by determination errors during the measurements. Therefore, this study quantifies the causes of these deviations by performing an inter-laboratory comparison on a metrological level between 3 national metrology institutes. Eventually this comparison helps to optimize the existing strategies and provides an enhanced technical practice for the determination of the calorific value by bomb calorimetry. It has been found that by assuring that the equilibrium moisture content of the samples is reached and that by avoiding the sources of error during the measurements, the repeatability of the samples can be improved by up to 50%. Consequently, this improvement will help to lower the final uncertainty by 10-25%.

Persevering with home rehabilitation exercise is a struggle for millions of people in the US each year. A key factor that may influence motivation to engage with rehabilitation exercise is the challenge level of the assigned exercises, but this hypothesis is currently supported only by subjective, self-report. Here, we studied the relationship between challenge level and perseverance using long-term, self-determined exercise patterns of a large number of individuals (N = 2,581) engaging in home rehabilitation with a sensor-based exercise system without formal supervision. FitMi is comprised of two puck-like sensors and a library of 40 gamified exercises for the hands, arms, trunk, and legs that are designed for people recovering from a stroke. We found that individuals showed the greatest perseverance with the system over a 2-month period if they had (1) a moderate level of motor impairment and (2) high but not perfect success during the 1st week at completing the exercise game. Further, a steady usage pattern (vs. accelerating or decelerating use) was associated with more overall exercise, and declines in exercise amount over time were associated with exponentially declining session initiation probability rather than decreasing amounts of exercise once a session was initiated. These findings confirm that an optimized challenge level and regular initiation of exercise sessions predict achievement of a greater amount of overall rehabilitation exercise in a group of users of commercial home rehabilitation technology and suggest how home rehabilitation programs and exercise technologies can be optimized to promote perseverance.

This work presents a study of the effects that integration of electrolysis facilities for Power-to-X processes have on the power grid. The novel simulation setup combines a high-resolution grid optimization model and a detailed scheduling model for alkaline water electrolysis. The utilization and congestion of power lines in northern Germany is investigated by setting different installed capacities and production strategies of the electrolysis facility. For electrolysis capacities up to 300 MW (∼50 ktH2/a), local impacts on the grid are observed, while higher capacities cause supra-regional impacts. Thereby, impacts are defined as deviations from the average line utilization greater than 5%. In addition, the minimum line congestion is determined to coincide with the daily-constrained production strategy of the electrolysis facility. Our result show a good compromise for the integrated grid-facility operation with minimum production cost and reduced impact on the grid.

Birth weight (BW) has been shown to be influenced by both fetal and maternal factors and in observational studies is reproducibly associated with future risk of adult metabolic diseases including type 2 diabetes (T2D) and cardiovascular disease. These life-course associations have often been attributed to the impact of an adverse early life environment. Here, we performed a multi-ancestry genome-wide association study (GWAS) meta-analysis of BW in 153,781 individuals, identifying 60 loci where fetal genotype was associated with BW (P

UnlabelledIndividuals with chronic stroke have limited options for hand rehabilitation at home. Here, we sought to determine the feasibility and efficacy of home-based MusicGlove therapy. Seventeen participants with moderate hand impairment in the chronic phase of stroke were randomized to 3 wk of home-based exercise with either the MusicGlove or conventional tabletop exercises. The primary outcome measure was the change in the Box and Blocks test score from baseline to 1 mo posttreatment. Both groups significantly improved their Box and Blocks test score, but no significant difference was found between groups. The MusicGlove group did exhibit significantly greater improvements than the conventional exercise group in motor activity log quality of movement and amount of use scores 1 mo posttherapy (p = 0.007 and p = 0.04, respectively). Participants significantly increased their use of MusicGlove over time, completing 466 gripping movements per day on average at study end. MusicGlove therapy was not superior to conventional tabletop exercises for the primary end point but was nevertheless feasible and led to a significantly greater increase in self-reported functional use and quality of movement of the impaired hand than conventional home exercises.Clinical trial registrationClinicalTrials.gov; "Influence of Timing on Motor Learning"; NCT01769326; https://clinicaltrials.gov/ct2/show/NCT01769326.

Miscarriage affects around 15% of clinically confirmed pregnancies. Here the authors carry out a large genome-wide association study for sporadic and multiple consecutive miscarriage and suggest links with placental biology.

Abstract Background Endometriosis is a gynaecological condition characterised by immune cell infiltration and distinct inflammatory signatures found in the peritoneal cavity. In this study, we aim to characterise the immune microenvironment in samples isolated from the peritoneal cavity in patients with endometriosis. Methods We applied mass cytometry (CyTOF), a recently developed multiparameter single-cell technique, in order to characterise and quantify the immune cells found in peritoneal fluid and peripheral blood from endometriosis and control patients. Results Our results demonstrate the presence of more than 40 different distinct immune cell types within the peritoneal cavity. This suggests that there is a complex and highly heterogeneous inflammatory microenvironment underpinning the pathology of endometriosis. Stratification by clinical disease stages reveals a dynamic spectrum of cell signatures suggesting that adaptations in the inflammatory system occur due to the severity of the disease. Notably, among the inflammatory microenvironment in peritoneal fluid (PF), the presence of CD69+ T cell subsets is increased in endometriosis when compared to control patient samples. On these CD69+ cells, the expression of markers associated with T cell function are reduced in PF samples compared to blood. Comparisons between CD69+ and CD69− populations reveal distinct phenotypes across peritoneal T cell lineages. Taken together, our results suggest that both the innate and the adaptive immune system play roles in endometriosis. Conclusions This study provides a systematic characterisation of the specific immune environment in the peritoneal cavity and identifies cell immune signatures associated with endometriosis. Overall, our results provide novel insights into the specific cell phenotypes governing inflammation in patients with endometriosis. This prospective study offers a useful resource for understanding disease pathology and opportunities for identifying therapeutic targets.

Background Obesity is observationally associated with altered risk of many female reproductive conditions. These include polycystic ovary syndrome (PCOS), abnormal uterine bleeding, endometriosis, infertility, and pregnancy-related disorders. However, the roles and mechanisms of obesity in the aetiology of reproductive disorders remain unclear. Thus, we aimed to estimate observational and genetically predicted causal associations between obesity, metabolic hormones, and female reproductive disorders. Methods and findings Logistic regression, generalised additive models, and Mendelian randomisation (MR) (2-sample, non-linear, and multivariable) were applied to obesity and reproductive disease data on up to 257,193 women of European ancestry in UK Biobank and publicly available genome-wide association studies (GWASs). Body mass index (BMI), waist-to-hip ratio (WHR), and WHR adjusted for BMI were observationally (odds ratios [ORs] = 1.02–1.87 per 1-SD increase in obesity trait) and genetically (ORs = 1.06–2.09) associated with uterine fibroids (UF), PCOS, heavy menstrual bleeding (HMB), and pre-eclampsia. Genetically predicted visceral adipose tissue (VAT) mass was associated with the development of HMB (OR [95% CI] per 1-kg increase in predicted VAT mass = 1.32 [1.06–1.64], P = 0.0130), PCOS (OR [95% CI] = 1.15 [1.08–1.23], P = 3.24 × 10−05), and pre-eclampsia (OR [95% CI] = 3.08 [1.98–4.79], P = 6.65 × 10−07). Increased waist circumference posed a higher genetic risk (ORs = 1.16–1.93) for the development of these disorders and UF than did increased hip circumference (ORs = 1.06–1.10). Leptin, fasting insulin, and insulin resistance each mediated between 20% and 50% of the total genetically predicted association of obesity with pre-eclampsia. Reproductive conditions clustered based on shared genetic components of their aetiological relationships with obesity. This study was limited in power by the low prevalence of female reproductive conditions among women in the UK Biobank, with little information on pre-diagnostic anthropometric traits, and by the susceptibility of MR estimates to genetic pleiotropy. Conclusions We found that common indices of overall and central obesity were associated with increased risks of reproductive disorders to heterogenous extents in a systematic, large-scale genetics-based analysis of the aetiological relationships between obesity and female reproductive conditions. Our results suggest the utility of exploring the mechanisms mediating the causal associations of overweight and obesity with gynaecological health to identify targets for disease prevention and treatment. Using observational and Mendelian randomization approaches, Samvida Venkatesh and colleagues investigate associations between obesity, metabolic factors, and female reproductive conditions. Author summary Why was this study done? Female reproductive disorders are common, yet relatively understudied, conditions with a large impact on women’s health and overall well-being. Obesity has previously been associated with the risk of developing female reproductive conditions, but estimates may be biased by weight gain caused by the disease or its treatment, as well as confounding environmental and lifestyle factors. What did the researchers do and find? In one of the largest publicly available datasets on human health, which includes up to 250,000 women, we saw positive associations between obesity and a range of female reproductive disorders, including uterine fibroids, polycystic ovary syndrome, heavy menstrual bleeding, and pre-eclampsia. We found that inherited genetic variation that is associated with obesity is also associated with female reproductive disorders, but the strength of these associations differs by type of obesity and reproductive condition. As genetic variants are randomly assigned at birth, this is a method to estimate the effect of obesity on reproductive conditions unbiased by environmental and lifestyle factors or reverse causation. Hormones such as leptin, which is secreted by fat cells, and insulin were found to mediate the genetic association of obesity with pre-eclampsia. What do these findings mean? Genetics-based investigations such as these provide support for the role of obesity in increasing the risk of reproductive conditions, reinforcing the need to address rising obesity rates in the population. Increased obesity and insulin resistance are potentially modifiable risk factors, and addressing these risk factors could help mitigate or treat female reproductive disorders, but further research must confirm that their manipulation influences risk of disease.

Abdominal hernias are common and characterised by the abnormal protrusion of a viscus through the wall of the abdominal cavity. The global incidence is 18.5 million annually and there are limited non-surgical treatments. To improve understanding of common hernia aetiopathology, we performed a six-stage genome-wide association study (GWAS) of 62,637 UK Biobank participants with either single or multiple hernia phenotypes including inguinal, femoral, umbilical and hiatus hernia. Additionally, we performed multivariable meta-analysis with metaUSAT, to allow integration of summary data across traits to generate combined effect estimates. On individual hernia analysis, we identified 3404 variants across 38 genome-wide significant (p < 5×10-8) loci of which 11 are previously unreported. Robust evidence for five shared susceptibility loci was discovered: ZC3H11B, EFEMP1, MHC region, WT1 and CALD1. Combined hernia phenotype analyses with additional multivariable meta-analysis of summary statistics in metaUSAT revealed 28 independent (seven previously unreported) shared susceptibility loci. These clustered in functional categories related to connective tissue and elastic fibre homeostasis. Weighted genetic risk scores also correlated with disease severity suggesting a phenotypic-genotypic severity correlation, an important finding to inform future personalised therapeutic approaches to hernia.

Summary: Background: We undertook a Grand Challenges in Global Eye Health prioritisation exercise to identify the key issues that must be addressed to improve eye health in the context of an ageing population, to eliminate persistent inequities in health-care access, and to mitigate widespread resource limitations. Methods: Drawing on methods used in previous Grand Challenges studies, we used a multi-step recruitment strategy to assemble a diverse panel of individuals from a range of disciplines relevant to global eye health from all regions globally to participate in a three-round, online, Delphi-like, prioritisation process to nominate and rank challenges in global eye health. Through this process, we developed both global and regional priority lists. Findings: Between Sept 1 and Dec 12, 2019, 470 individuals complete round 1 of the process, of whom 336 completed all three rounds (round 2 between Feb 26 and March 18, 2020, and round 3 between April 2 and April 25, 2020) 156 (46%) of 336 were women, 180 (54%) were men. The proportion of participants who worked in each region ranged from 104 (31%) in sub-Saharan Africa to 21 (6%) in central Europe, eastern Europe, and in central Asia. Of 85 unique challenges identified after round 1, 16 challenges were prioritised at the global level; six focused on detection and treatment of conditions (cataract, refractive error, glaucoma, diabetic retinopathy, services for children and screening for early detection), two focused on addressing shortages in human resource capacity, five on other health service and policy factors (including strengthening policies, integration, health information systems, and budget allocation), and three on improving access to care and promoting equity. Interpretation: This list of Grand Challenges serves as a starting point for immediate action by funders to guide investment in research and innovation in eye health. It challenges researchers, clinicians, and policy makers to build collaborations to address specific challenges. Funding: The Queen Elizabeth Diamond Jubilee Trust, Moorfields Eye Charity, National Institute for Health Research Moorfields Biomedical Research Centre, Wellcome Trust, Sightsavers, The Fred Hollows Foundation, The Seva Foundation, British Council for the Prevention of Blindness, and Christian Blind Mission. Translations: For the French, Spanish, Chinese, Portuguese, Arabic and Persian translations of the abstract see Supplementary Materials section.

Background: Urology, traditionally a maledominated specialty, keeping pace with the quickly changing gender landscape, has been characterized by waves of feminization. This study aims to understand the perspectives of women urologists on the obstacles to their career development, and the impact of such hurdles on their professional roles in urological education, practice, and leadership. Methods: 119 female urology residents/consultants were surveyed via a webinar-based platform, covering relevant questions on domains of Academia, Mentorship, Leadership, Parenting, and Charity. Statistical analysis was done using frequency distribution based on the responses. Results: 46.8% of the respondents felt that there is an under-representation of women in academia. ‘Having a good mentor’ was the most important factor for a novice to succeed in academia (68%). The most important trait in becoming a good leader was ‘good communication skills’ (35%), followed by ‘visionary’ (20%). The greatest challenge faced by leaders in the medical field was considered as ‘time management’ (31.9%). Only 21.2% of the participants felt difficulty in having a work-personal life balance, whereas 63.8% of them found it difficult only ‘sometimes’. As a working parent, ‘the guilt that they are not available all the time’ was considered the most difficult aspect (59.5%), and ‘more flexible schedule’ was needed to make their lives as a working parent easier (46.8%). 34% of the respondents were affiliated with some charitable organizations. The biggest drive to do charity was their satisfaction with a noble cause (72.3%). Conclusions: Need for increased encouragement and recruitment of females into urology, and to support and nurture them in their career aspirations.

A membrane reactor produces high-quality biodiesel by combining both reaction and separation in a single unit. However, the reactor has disadvantages such as high operating expense and reduced efficiency over time due to membrane fouling. To solve this issue, frequent cleaning with physical and chemical methods is required. Membrane cleaning contributes to the reactor’s operating cost to a large extent, including energy, chemicals and even production loss. Although there have been studies undertaken focusing on improving membrane cleaning, optimizing the performance of the membrane reactor in biodiesel production has received limited attention. In this work, a novel membrane cleaning model is presented and used to optimize the membrane reactor efficiency in terms of biodiesel yield and cleaning costs. The model captures the dynamic states of reversible and irreversible membrane fouling during the cleaning process. It is further used to evaluate the effects of backwashing and chemical cleaning on the membrane reactor. The results show that the number of backwashes during operation is a crucial factor to improve reactor productivity and reduce the cleaning cost. The membrane reactor’s operating time rose 2 to 3 times when the operating period between two backwashes, or an operating cycle, reduced from 70 min to 15 min. The biodiesel yield increased significantly due to the extended operation. However, longer operating time led to an accumulation of more irreversible fouling, which could not be removed by backwashing. The cost of chemical cleaning rose as the irreversible fouling level increased. Regarding the cost-to-yield ratio of the biodiesel reactor, the best operating conditions were found at the operating cycle of 25 minutes between 2 backwashes. Overall, the cleaning model allows the prediction and reduction of the cleaning expense of the membrane reactor, increasing its potential as a biodiesel production technology significantly.

In this work, we propose a mapping of suitable feedstock, products, and technologies used in various stages of algae biorefinery, including cultivation, harvesting, dewatering, drying, cell disruption, and extraction. The current technologies at each interval are studied and compared with each other. To set up, compare and select the most promising production pathways, a superstructure is proposed. A superstructure of algae biorefinery based on a literature review is developed and presented. Due to the significant impact of the environment on compositions and the number of microalgae, the effect of two factors i.e., light intensity and nutrient composition, on biomass production efficiency are critical. We will further demonstrate the potential application of algae as source for various products such as cosmetic ingredients, nutraceuticals (e.g., carotenoids and proteins), energy carriers (e.g., biodiesel, bioethanol, biohydrogen, biogas) and fertilizer.