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Background: The presence of dental caries impacts on children's daily lives, particularly among those living in deprived areas. There are successful interventions across the United Kingdom for young children based on toothbrushing with fluoride toothpaste. However, evidence is lacking for oral health improvement programmes in secondary-school pupils to reduce dental caries and its sequelae., Objectives: To determine the clinical and cost effectiveness of a behaviour change intervention promoting toothbrushing for preventing dental caries in secondary-school pupils., Design: A multicentre, school-based, assessor-blinded, two-arm cluster randomised controlled trial with an internal pilot and embedded health economic and process evaluations., Setting: Secondary schools in Scotland, England and Wales with above-average proportion of pupils eligible for free school meals. Randomisation occurred within schools (year-group level), using block randomisation stratified by school., Participants: Pupils aged 11-13 years at recruitment, who have their own mobile telephone., Interventions: Two-component intervention based on behaviour change theory: (1) 50-minute lesson delivered by teachers, and (2) twice-daily text messages to pupils' mobile phones about toothbrushing, compared with routine education., Main Outcome Measures: Primary outcome: presence of at least one treated or untreated carious lesion using D ICDAS4-6 MFT (Decayed, Missing and Filled Teeth) in any permanent tooth, measured at pupil level at 2.5 years. Secondary outcomes included: number of D ICDAS4-6 MFT; presence and number of D ICDAS1-6 MFT; plaque; bleeding; twice-daily toothbrushing; health-related quality of life (Child Health Utility 9D); and oral health-related quality of life (Caries Impacts and Experiences Questionnaire for Children)., Results: Four thousand six hundred and eighty pupils (intervention, n  = 2262; control, n  = 2418) from 42 schools were randomised. The primary analysis on 2383 pupils (50.9%; intervention 1153, 51.0%; control 1230, 50.9%) with valid data at baseline and 2.5 years found 44.6% in the intervention group and 43.0% in control had obvious decay experience in at least one permanent tooth. There was no evidence of a difference (odds ratio 1.04, 95% confidence interval 0.85 to 1.26, p  = 0.72) and no statistically significant differences in secondary outcomes except for twice-daily toothbrushing at 6 months (odds ratio 1.30, 95% confidence interval 1.03 to 1.63, p  = 0.03) and gingival bleeding score (borderline) at 2.5 years (geometric mean difference 0.92, 95% confidence interval 0.85 to 1.00, p  = 0.05). The intervention had higher incremental mean costs (£1.02, 95% confidence interval -1.29 to 3.23) and lower incremental mean quality-adjusted life-years (-0.003, 95% confidence interval -0.009 to 0.002). The probability of the intervention being cost-effective was 7% at 2.5 years. However, in two subgroups, pilot trial schools and schools with higher proportions of pupils eligible for free school meals, there was an 84% and 60% chance of cost effectiveness, respectively, although their incremental costs and quality-adjusted life-years remained small and not statistically significant. The process evaluation revealed that the intervention was generally acceptable, although the implementation of text messages proved challenging. The COVID-19 pandemic hampered data collection. High rates of missing economic data mean findings should be interpreted with caution., Conclusions: Engagement with the intervention and evidence of 6-month change in toothbrushing behaviour was positive but did not translate into a reduction of caries. Future work should include work with secondary-school pupils to develop an understanding of the determinants of oral health behaviours, including toothbrushing and sugar consumption, particularly according to free school meal eligibility., Trial Registration: This trial is registered as ISRCTN12139369., Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 15/166/08) and is published in full in Health Technology Assessment ; Vol. 28, No. 52. See the NIHR Funding and Awards website for further award information.

Purpose: In patients with a need for frequent but intermittent apheresis, vascular access can prove challenging. We describe the migration of the use of a Vortex LP dual lumen port (Angiodynamics, Latham, NY) to one Powerflow and one ClearVUE power injectable port (Becton Dickinson, Franklin Lakes, NJ) in a series of patients undergoing intermittent apheresis., Materials and Methods: All patients had a need for long-term intermittent apheresis. Eight had double lumen Vortex port (pre) and were exchanged for one Powerflow port and one conventional subcutaneous venous port with 90° needle entry (post) while 12 did not have any port in place and received the same configuration. IRB approval was granted. We recorded the treatment time, flow rate, and tissue plasminogen activator (tPA) use for five treatment sessions after placement. When available, we compared five treatments with the Vortex port and the new configuration., Results: The mean treatment time is reduced with the new configuration (P = 0.0033). The predicted mean treatment time, adjusting for gender, race, BMI and age and accounting for correlations within a patient is 91.18 min pre and 77.96 min post. The flow rate is higher with the new configuration (P < 0.0001). The predicted mean flow rate in mL/min is 61.59 for the Vortex port and 71.89 for the new configuration. tPA use was eliminated in the population converted from Vortex ports and had a 48% reduction when compared to all other configurations in the study., Conclusion: The introduction of a novel device configuration of venous access ports for intermittent apheresis resulted in higher flow rates and less total time for treatment. Use of tPA was greatly reduced. These results suggest that the new configuration could result in less expense for the hospital and better throughput in a busy pheresis practice. Clinical trial registration with ClinicalTrials.gov: NCT04846374., (© 2024 Wiley Periodicals LLC.)

Objectives: This multicentre, assessor-blinded, two-arm cluster randomized trial evaluated the clinical and cost-effectiveness of a behaviour change intervention promoting toothbrushing for preventing dental caries in UK secondary schools., Methods: Pupils aged 11-13 years with their own mobile telephone attending secondary schools with above average free school meals eligibility were randomized (at year-group level) to receive a lesson and twice-daily text messages or to usual care. Year-groups (n = 84) from 42 schools including 4680 pupils (intervention, n = 2262; control, n = 2418) were randomized., Results: In 2383 participants with valid data at baseline and 2.5 years, the primary outcome of presence of at least one treated or untreated carious lesion (D 4-6 MFT [Decayed, Missing and Filled Teeth] in permanent teeth using International Caries Detection and Assessment System) was 44.6% in the intervention group and 43.0% in control (odds ratio [OR] 1.04, 95% CI 0.85-1.26, p = .72). There were no statistically significant differences in secondary outcomes of presence of at least one treated or untreated carious lesion (D 1-6 MFT), number of D 4-6 MFT and D 1-6 MFT, plaque and bleeding scores or health-related- (Child Health Utility 9D) or oral health-related- quality of life (CARIES-QC). However, twice-daily toothbrushing, reported by 77.6% of pupils at baseline, increased at 6 months (intervention, 86.9%; control, 83.0%; OR 1.30, 95% CI 1.03-1.63, p = .03), but returned to no difference at 2.5 years (intervention, 81.0%; control, 79.9%; OR 1.05, 95% CI 0.84-1.30, p = .69). Estimated incremental costs and quality-adjusted life-years (QALYs) of the intervention, relative to control, were £1.02 (95% CI -1.29 to 3.23) and -0.003 (95% CI -0.009 to 0.002), respectively, with a 7% chance of being cost-effective (£20 000/QALY gained threshold)., Conclusion: There was no evidence of statistically significant difference for caries prevalence at 2.5-years. The intervention's positive 6-month toothbrushing behaviour change did not translate into caries reduction. (ISRCTN 12139369). COVID-19 pandemic adversly affected follow-up., (© 2024 The Authors. Community Dentistry and Oral Epidemiology published by John Wiley & Sons Ltd.)

Background: Libraries provide public access to information that may be used to inform healthcare decisions. Exploring the health information needs of library-users could improve community health outcomes, especially during times of crisis like the COVID-19 pandemic., Objective: The purpose of this study was to identify the health information needs of library-users to explore the potential role of libraries in advancing community health., Methods: A quantitative, descriptive, cross-sectional survey was employed., Results: One hundred and fifty participants in the (Memphis) Tennessee metropolitan area, ranging from 18 to 84 years of age, completed the survey between September 2020 and April 2021. Most respondents reported seeking physical and mental health-related information from libraries. In addition, nearly half of respondents reported delaying medical care due to risk of exposure to COVID-19, cost or appointment issues., Discussion: Study results indicated that there were urgent health information needs among library-users in this community, that COVID-19 further limited or delayed access to information, and that library-users accessed health information during library visits., Conclusion: Public libraries have the potential to serve as information hubs to improve community health outcomes. Additional research should be conducted to collect qualitative community health information needs and the ways in which public library systems can address them., (© 2024 Health Libraries Group.)

Background: A number of children experience difficulties with social communication and this has long-term deleterious effects on their mental health, social development and education. The E-PLAYS-2 study will test an intervention ('E-PLAYS') aimed at supporting such children. E-PLAYS uses a dyadic computer game to develop collaborative and communication skills. Preliminary studies by the authors show that E-PLAYS can produce improvements in children with social communication difficulties on communication test scores and observed collaborative behaviours. The study described here is a definitive trial to test the effectiveness and cost-effectiveness of E-PLAYS delivered by teaching assistants in schools., Methods: The aim of the E-PLAYS-2 trial is to establish the effectiveness and cost-effectiveness of care as usual plus the E-PLAYS programme, delivered in primary schools, compared to care as usual. Cluster-randomisation will take place at school level to avoid contamination. The E-PLAYS intervention will be delivered by schools' teaching assistants. Teachers will select suitable children (ages 5-7 years old) from their schools using guidelines provided by the research team. Assessments will include blinded language measures and observations (conducted by the research team), non-blinded teacher-reported measures of peer relations and classroom behaviour and parent-reported use of resources and quality of life. A process evaluation will also include interviews with parents, children and teaching assistants, observations of intervention delivery and a survey of care as usual. The primary analysis will compare pragmatic language scores for children who received the E-PLAYS intervention versus those who did not at 40 weeks post-randomisation. Secondary analyses will assess cost-effectiveness and a mixed methods process evaluation will provide richer data on the delivery of E-PLAYS., Discussion: The aim of this study is to undertake a final, definitive test of the effectiveness of E-PLAYS when delivered by teaching assistants within schools. The use of technology in game form is a novel approach in an area where there are currently few available interventions. Should E-PLAYS prove to be effective at the end of this trial, we believe it is likely to be welcomed by schools, parents and children., Trial Registration: ISRCTN 17561417, registration date 19th December 2022., Protocol Version: v1.1 19th June 2023., (© 2024. The Author(s).)

Objective: Smell and taste disorders among patients with COVID-19 has become increasingly reported in the literature, however the prevalence varies. Post-infectious respiratory dysfunction has also been linked to influenza. In this study, we aimed to compare the rates of smell and taste disorders between COVID-19 and Influenza in unvaccinated patients., Study Design: Retrospective cohort study., Setting: TriNetX research network., Methods: Two queries were made on 7/1/2023 to include Influenza without a diagnosis of COVID-19 and a COVID-19 without a diagnosis of Influenza. The queries included patients from January 1 to December 31, 2022 from 102 Healthcare Organizations. The resultant population of patients with ICD-10 codes for COVID-19 and Influenza were matched using demographic characteristics to evaluate the risk of smell disorders., Results: The overall 3-month incidence of smell and taste disorders was 0.73 % in the COVID-19 population and 0.1 % in the influenza population. The 3-month matched risk ratios were 11.1 [95 % CI (8.8,13.8)]; p < 0.001) times higher for disorders of the smell and taste secondary to COVID-19 compared to influenza., Conclusions: Disorders of the smell and taste are more common among patients with COVID-19 compared to patients with Influenza. Beyond smell loss, patients experience additional nasal and sinus-related rhinological symptoms, pointing to COVID-19's and influenza's wider impact on overall rhinological health. We believe that due to the transient nature of these disorders, they might go underreported., Competing Interests: Conflicts of interest The authors deny any conflicts of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Purpose: Endocrine-based therapy is the initial primary treatment option for hormone receptor-positive and human epidermal growth factor receptor 2-negative (HR+/HER2-) metastatic breast cancer (mBC). However, patients eventually experience disease progression due to resistance to endocrine therapy. Molibresib (GSK525762) is a small-molecule inhibitor of bromodomain and extraterminal (BET) family proteins (BRD2, BRD3, BRD4, and BRDT). Preclinical data suggested that the combination of molibresib with endocrine therapy might overcome endocrine resistance. This study aimed to investigate the safety, tolerability, pharmacokinetics, pharmacodynamics, and efficacy [objective response rate (ORR)] of molibresib combined with fulvestrant in women with HR+/HER2- mBC., Patients and Methods: In this phase I/II dose-escalation and dose-expansion study, patients received oral molibresib 60 or 80 mg once daily in combination with intramuscular fulvestrant. Patients enrolled had relapsed/refractory, advanced/metastatic HR+/HER2- breast cancer with disease progression on prior treatment with an aromatase inhibitor, with or without a cyclin-dependent kinase 4/6 inhibitor., Results: The study included 123 patients. The most common treatment-related adverse events (AE) were nausea (52%), dysgeusia (49%), and fatigue (45%). At a 60-mg dosage of molibresib, >90% of patients experienced treatment-related AE. Grade 3 or 4 treatment-related AE were observed in 47% and 48% of patients treated with molibresib 60 mg and molibresib 80 mg, respectively. The ORR was 13% [95% confidence interval (CI), 8-20], not meeting the 25% threshold for proceeding to phase II. Among 82 patients with detected circulating tumor DNA and clinical outcome at study enrollment, a strong association was observed between the detection of copy-number amplification and poor progression-free survival (HR, 2.89; 95% CI, 1.73-4.83; P < 0.0001)., Conclusions: Molibresib in combination with fulvestrant did not demonstrate clinically meaningful activity in this study., (©2023 The Authors; Published by the American Association for Cancer Research.)

Background This paper describes the sociodemographics and oral health of UK secondary school pupils. They were participants of the BRIGHT trial, which was designed to evaluate the effectiveness of a toothbrushing intervention to reduce dental caries.Methods Overall, 4,680 pupils aged 11-13 years attending 42 secondary schools in England, Scotland and Wales with above average proportion of pupils eligible for free school meals, were recruited to the trial. Sociodemographic data were collected. Participants had a clinical assessment for caries, plaque and bleeding and completed measures of oral and general health-related quality of life and oral health behaviours (frequency of toothbrushing, dental attendance and cariogenic food/drinks consumed). Regression analyses were performed.Results Over one-third (34.7%) of participants had caries experience, with 44.5% reporting their oral health had an impact on their daily lives. Factors associated with a statistically significant increased likelihood of caries experience were older age, being female, eligibility for free school meals, worse oral health-related quality of life, higher cariogenic diet, less than twice-daily toothbrushing, living in a more deprived area and lower school attendance.Conclusions The prevalence and impact of dental caries on the lives of pupils remains high, with further oral health promotion activities needed in targeted secondary schools., (© 2023. The Author.)

A 6 yr old male castrated American Staffordshire terrier was referred for a nonhealing wound at the site of a previously incompletely excised, high-grade soft tissue sarcoma. Physical examination revealed right popliteal lymphadenopathy and a fungating mass of the right pelvic limb at the level of the hock. Thoracic and abdominal computed tomography revealed mild lymphadenopathy of multiple iliac and inguinal lymph nodes. Right pelvic limb amputation and inguinal lymphadenectomy were performed. Histopathology was consistent of a high-grade soft tissue sarcoma with diffuse spread through the lymphatic vessels of the right pelvic limb up to the right inguinal lymph node but not affecting the lymph node itself. Doxorubicin chemotherapy was elected postoperatively as adjuvant therapy. Approximately 4 mo following initiation of chemotherapy, the patient developed a firm, tubular subcutaneous mass starting near the previous amputation site with tracking toward the thorax. Fine needle aspiration of the new mass was consistent with atypical spindle cell proliferation. Palliative care was elected, and the patient was euthanized 3 mo later because of progressive disease. In-transit metastasis is a rare behavior for soft tissue sarcomas across all species, and this is the first report of such a presentation for canine soft tissue sarcoma., (© 2023 by American Animal Hospital Association.)

Ferroptosis is a non-apoptotic form of regulated cell death that is triggered by the discoordination of regulatory redox mechanisms culminating in massive peroxidation of polyunsaturated phospholipids. Ferroptosis inducers have shown considerable effectiveness in killing tumour cells in vitro, yet there has been no obvious success in experimental animal models, with the notable exception of immunodeficient mice 1,2 . This suggests that the effect of ferroptosis on immune cells remains poorly understood. Pathologically activated neutrophils (PMNs), termed myeloid-derived suppressor cells (PMN-MDSCs), are major negative regulators of anti-tumour immunity 3-5 . Here we found that PMN-MDSCs in the tumour microenvironment spontaneously die by ferroptosis. Although decreasing the presence of PMN-MDSCs, ferroptosis induces the release of oxygenated lipids and limits the activity of human and mouse T cells. In immunocompetent mice, genetic and pharmacological inhibition of ferroptosis abrogates suppressive activity of PMN-MDSCs, reduces tumour progression and synergizes with immune checkpoint blockade to suppress the tumour growth. By contrast, induction of ferroptosis in immunocompetent mice promotes tumour growth. Thus, ferroptosis is a unique and targetable immunosuppressive mechanism of PMN-MDSCs in the tumour microenvironment that can be pharmacologically modulated to limit tumour progression., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

PLAIN LANGUAGE SUMMARY What is the context? Herpes zoster or shingles and its complications such as postherpetic neuralgia - a painful condition that affects the nerve fibers and skin - may lead to complex pain that can be addressed using opioids in some patients.The recombinant zoster vaccine (RZV) vaccine prevents shingles and, therefore, may reduce the use of opioids and the negative health outcomes and costs associated with it. What is new? In this retrospective medical claims study, including patients between 2012 and 2017, we evaluated the receipt of pain medication including opioids in herpes zoster patients, and assessed factors associated with opioid prescription.estimated health care resource utilization and costs associated with opioid use among patients with herpes zoster.assessed the impact of vaccination on opioid prescriptions.Among subjects receiving opioids, 78.5% started with a weak opioid dose. Dose escalation was uncommon.Postherpetic neuralgia, immunocompromised status, and comorbidities are the main risk factors associated with opioid prescription.Health care costs are almost double in patients with herpes zoster receiving opioids compared with patients without an opioid prescription.In a population of 1 million adults aged 50 years or older, vaccination with the recombinant zoster vaccine could prevent over 19,000 patients from receiving opioids. What is the impact? Prevention of herpes zoster through vaccination may be a highly effective strategy to reduce opioid prescriptions and costs related to pain management in a susceptible population.Increasing RZV vaccination coverage in adults aged ≥50 years may further reduce potential opioid prescriptions through a decrease in shingles incidence.

Background: Prior to exercise, a warm-up routine has been suggested to be an imperative factor in task readiness with the anticipation that it will enhance performance. One of the key benefits of a warm-up is the increase in muscle and core temperature, which can be achieved in a variety of ways. An effective way to achieve improvements in core and muscle temperature is by performing an active warm-up. However, lengthy transition periods between an active warm-up and exercise performance are known to cause a decline in core and muscle temperature, thereby reducing performance capability. As such, methods are needed to assist athletes during transition periods, to maintain the benefits of a warm-up with the aim of optimising performance. Accordingly, the purpose of this review is to systematically analyse the evidence base that has investigated the use of passive heating to aide sporting performance when a transition period is experienced., Methods: A systematic review and meta-analysis were undertaken following relevant studies being identified using PubMed, Web of Science, and EBSCO. Studies investigating the effects of passive heating strategies during the transition period between an active warm-up and exercise performance were included. The quality of the included studies were assessed by two independent reviewers using a modified version of the Physiotherapy Evidence Database scale., Results: Seven studies, all high quality (mean = 7.6), reported sufficient data (quality score > 5) on the effects of passive heating strategies on exercise performance, these studies consisted of 85 well-trained athletes (78 male and 7 female). Passive heating strategies used between an active warm-up and exercise, significantly increased peak power output in all studies (ES = 0.54 [95% CI 0.17 to 0.91]). However, only a favourable trend was evident for exercise performance (ES = 1.07 [95% CI - 0.64 to 0.09])., Conclusions: Based upon a limited number of well-conducted, randomised, controlled trials, it appears that passive heating strategies used between an active warm-up and exercise have a positive impact on peak power output. Although, additional research is necessary to determine the optimum procedure for passive warm-up strategies., (© 2022. The Author(s).)

Objectives: To reveal hearing loss patterns in patients with enlarged vestibular aqueduct (EVA) syndrome according to demographic and clinical characteristics., Methods: A retrospective, longitudinal study design was utilized to identify patients with EVA. Ears of patients were categorized into one of four cohorts: progressive fluctuating, progressive non-fluctuating, stable fluctuating, and stable non-fluctuating patterns. Pairwise and group comparisons were performed with non-parametric tests to assess vestibular aqueduct (VA) morphology, clinical, and demographic variables between hearing loss pattern cohorts. Rates of hearing loss in the subgroups were determined utilizing a mixed linear effects model., Results: 44 patients (25 female, 19 male, median diagnosis age: 8.06 years) met inclusion criteria. 16 individuals demonstrated unilateral EVA and 29 had bilateral EVA, resulting in 74 total ears with EVA. Amongst the four cohorts, differences in operculum widths amongst groups were statistically significant (p = 0.049) while VA midpoint widths were not (p = 0.522). Progressive hearing loss ears without fluctuations demonstrated a 3.20 dB per year (p < 0.001) progression while progressive hearing loss ears with fluctuations reported a rate of 3.52 dB loss per year (p < 0.001)., Conclusion: Hearing fluctuations occur similarly in EVA patients with stable and progressive hearing loss. With the exception of increased rates of hearing loss progression for fluctuating progressive hearing loss patients, vestibular aqueduct morphology, demographic, and clinical characteristics commonly reported are likely not strong predictors for whether patients will or will not experience fluctuating patterns of hearing loss., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Objectives: |The aim of this study was to evaluate the use of volumetric HRCT measurements in the diagnosis of enlarged vestibular aqueduct syndrome (EVAS) and describe the association of this novel radiographic approach with clinical hearing outcomes. We hypothesized that volumetric measurements may have stronger correlation to hearing loss given the anatomic variability of the vestibular aqueduct in linear measurements., Methods: A retrospective study design was used, including 51 patients that fit the inclusion criteria for the study for a total of 81 ears. 3D volumes were calculated using the MIM Software platform (MIM Software Inc.) from semiautomatic segmentation of the VA across individual slices on CT scan. Air and bone conduction data was collected from medical records with the air-bone gap being calculated from these data. Univariate and multivariate analyses were conducted to determine if volumetric VA size correlated with hearing loss outcomes., Results: Out of the study population, 30 subjects (58.8%) demonstrated bilateral EVA. Average VA size estimated by volumetric CT methodology was 0.035 mm 3 ; sd = 0.025 mm 3 . Volumetric measurements significantly correlated to both midpoint length and operculum size. Multivariate analysis adjusting for age, race, and gender demonstrated significant correlation between volumetric VA size and both low and high frequencies for PTA Air (p = 0.009; 0.010) and PTA Bone (p = 0.027; 0.002), respectively. Of note, the coefficient values for volumetric data were higher than linear measurements showing a potentially stronger correlation, albeit with high variability. Volumetric size was not significantly correlated to air-bone gap at either low or high frequency (p = 0.335; 0.062)., Conclusion: Our results indicate that volumetric CT measurements of the VA may be a valid and viable new method for assessing EVAS patients. In our study, volumetric VA measurements demonstrated a strong correlation across both air and bone conduction at both frequency ranges measured, with potentially greater correlative strength than linear measurements., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Introduction: Although non-Hispanic Black women have increased risks of adverse birth outcomes compared with non-Hispanic white women in the United States, there is a lack of research specifically focusing on non-Hispanic Black women. Thus, this study's purpose was to evaluate whether place of birth and type of attendant used during labor is associated with having a newborn born small for gestational age (SGA) among non-Hispanic Black Medicaid recipients., Methods: This study used 2017 Natality data from the National Vital Statistics System for non-Hispanic Black women who used Medicaid as a source of payment (N = 322,604). Type of attendant (ie, the medical professional who assisted during childbirth), place of birth (ie, setting where the woman gave birth), maternal factors, and SGA were obtained from birth certificates. We used multivariate logistic regression to investigate the association between place of birth, type of birth attendant, and newborns born SGA., Results: After adjustment, women who used a certified nurse-midwife or other midwife as an attendant during labor had statistically significant decreased odds of having a neonate born SGA compared with those who had a physician as an attendant (odds ratio [OR], 0.69; 95% CI, 0.66-0.71 and OR, 0.68; 95% CI, 0.55-0.85, respectively). Those who gave birth in a birthing center or had planned home births also had statistically significant decreased odds of having a neonate born SGA (OR, 0.52; 95% CI, 0.38-0.69 and OR, 0.37; 95% CI, 0.21-0.66, respectively). However, those who had an unplanned home birth had twice the odds of having a neonate born SGA compared with those who gave birth at a hospital or clinic (OR, 2.00; 95% CI, 1.50-2.64)., Discussion: Given the racial disparity in adverse birth outcomes for non-Hispanic Black women, the observed associations provide justification for future research to determine whether birthing location and birth attendant are related to SGA., (© 2022 by the American College of Nurse-Midwives.)

Objective: The objective of this study is to identify the incidence of and risk factors for urinary tract infection (UTI) after office cystoscopy and urodynamic studies (UDS) in a female population., Methods: This was a retrospective cohort study investigating incidence of and risk factors for UTI after office testing. Inclusion criteria included women presenting for either cystoscopy or UDS from September 2019 to February 2020. Modified Poisson regression with robust error variance was used to identify risk factors for UTI after cystoscopy and UDS in a female population., Results: A total of 274 patients met inclusion criteria. One hundred eighty-five patients underwent office cystoscopy. Nine (4.8%) had a postcystoscopy UTI. Significant risk factors for postcystoscopy UTI included recurrent UTI (relative risk, 7.51; 95% confidence interval, 1.66-34.05) and a history of interstitial cystitis (relative risk, 4.56; 95% confidence interval, 1.52-13.73). Of those with recurrent UTI, 13.7% had a postcystoscopy UTI. Among patients with interstitial cystitis, 25% had a postcystoscopy UTI. One hundred ninety-two patients underwent UDS. Ten (5.2%) developed a post-UDS UTI. No risk factors were identified., Conclusions: Patients with recurrent UTI were 7.51 times more likely to develop a UTI after cystoscopy, whereas those with interstitial cystitis were 4.56 times more likely to develop a UTI after cystoscopy. The incidence of UTI after UDS was low overall. Understanding who is at higher risk of postprocedural UTIs may help identify subpopulations that may benefit from prophylactic strategies., Competing Interests: The authors have declared that there are no conflicts of interest., (Copyright © 2022 American Urogynecologic Society. All rights reserved.)

High precision measurements of the polarized electron beam-spin asymmetry in semi-inclusive deep inelastic scattering (SIDIS) from the proton have been performed using a 10.6 GeV incident electron beam and the CLAS12 spectrometer at Jefferson Lab. We report here a high precision multidimensional study of single π^{+} SIDIS data over a large kinematic range in Bjorken x, fractional energy, and transverse momentum of the hadron as well as photon virtualities Q^{2} ranging from 1-7  GeV^{2}. In particular, the structure function ratio F&#95;{LU}^{sinϕ}/F&#95;{UU} has been determined, where F&#95;{LU}^{sinϕ} is a twist-3 quantity that can reveal novel aspects of emergent hadron mass and quark-gluon correlations within the nucleon. The data's impact on the evolving understanding of the underlying reaction mechanisms and their kinematic variation is explored using theoretical models for the different contributing transverse momentum dependent parton distribution functions.

The financial considerations of becoming a physician are often not fully understood or appreciated until after residency and fellowship training. Once training is complete, physicians face a combination of increased financial rewards mixed with significant, and seemingly overwhelming, financial responsibilities, often with limited financial knowledge or understanding. Appropriately managing debt obligations, living expenses, saving for retirement, children's education, and establishing financial safety nets through savings, investments, and insurance are critical. This article is a starting point to provide the new physician with an introduction into some of those financial considerations, to both encourage further learning and promote successful financial decisions., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Strange matter is believed to exist in the cores of neutron stars based on simple kinematics. If this is true, then hyperon-nucleon interactions will play a significant part in the neutron star equation of state. Yet, compared to other elastic scattering processes, there is very little data on Λ-N scattering. This experiment utilized the CEBAF Large Acceptance Spectrometer (CLAS) detector to study the Λp→Λp elastic scattering cross section in the incident Λ momentum range 0.9-2.0  GeV/c. These are the first data on this reaction since the 1970s. The new cross sections have significantly better accuracy and precision than the existing world data, and the techniques developed here can also be used in future experiments.

Multiple myeloma is a progressive and incurable hematologic malignancy. It is predominantly a disease of older individuals, with a third of these patients considered to be elderly. In recent years, there has been a focus and emphasis on identifying and stratifying patients based on their functional status and frailty. There are several hallmark complications of the disease-hypercalcemia, renal insufficiency, anemia, bone pain-along with thromboembolism and compromised immunity that are common in patients with multiple myeloma. Due to the wide range of patient ages and functional status, there are, accordingly, different considerations for management of the above complications based on numerous factors, including frailty status. This review focuses on considerations and management of common complications of multiple myeloma in elderly patients. These include renal failure, skeletal complications, anemia, thromboembolism, and infectious complications., Competing Interests: Disclosure The authors have no conflicts of interest to disclose., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Since 1997, sediment metal concentrations have been monitored in the Alberta Oil Sands Region (AOSR) of the Lower Athabasca River by the Regional Aquatics Monitoring Program (RAMP; 1997-2002), the Joint Oil Sands Monitoring Program (JOSM; 2012-2014), and the Oil Sands Monitoring Program (OSM; 2015-present). However, it has remained difficult to differentiate industrial sources from natural sources and quantify the extent of pollution due to inadequate knowledge of predevelopment reference conditions. Here, baselines were constructed using predevelopment (i.e., pre-1967) sediment concentrations of US EPA priority pollutants (Be, Cr, Cu, Ni, Pb) and V, an element elevated in bitumen and associated waste materials, normalized to Al concentration in cores from floodplain and upland lakes within the AOSR to characterize the natural range of variability. The Lower Athabasca River sediment metal monitoring data were examined in the context of the predevelopment baselines. Most metals are below the threshold for minimal enrichment (<1.5x baseline) except for chromium (up to 4.8x) in some RAMP samples. The predevelopment baselines for sediment metal concentrations will be of particular importance as the oil sands industry potentially shifts from a no-release policy to the treatment and release of oil sands process waters directly to the Lower Athabasca River.

Background: Antimicrobial resistance is a growing concern in canine Staphylococcus pseudintermedius dermatitis. Treatment with rifampicin (RFP) is considered only in meticillin-resistant and multidrug-resistant S. pseudintermedius (MDR-MRSP)., Hypothesis/objectives: To determine an optimal RFP dosing for MDR-MRSP treatment without induction of RFP resistance and identify causal mutations for antimicrobial resistance., Methods and Materials: Time-kill assays were performed in a control isolate and three MDR-MRSP isolates at six clinically relevant concentrations [32 to 1,024 × MIC (the minimum inhibitory concentration)]. Whole-genome resequencing and bioinformatic analysis were performed in the resistant strains developed in this assay., Results: The genomic analysis identified nine antimicrobial resistance genes (ARGs) in MDR-MRSP isolates, which are responsible for resistance to seven classes of antibiotics. RFP activity against all four isolates was consistent with a time-dependent and bacteriostatic response. RFP resistance was observed in six of the 28 time-kill assays, including concentrations 64 × MIC in MDR-MRSP1 isolates at 24 h, 32 × MIC in MDR-MRSP2 at 48 h, 32 × MIC in MDR-MRSP3 at 48 h and 256 × MIC in MDR-MRSP3 at 24 h. Genome-wide mutation analyses in these RFP-resistant strains discovered the causal mutations in the coding region of the rpoB gene., Conclusions and Clinical Relevance: A study has shown that 6 mg/kg per os results in plasma concentrations of 600-1,000 × MIC of S. pseudintermedius. Based on our data, this dose should achieve the minimum MIC (×512) to prevent RFP resistance development; therefore, we recommend a minimum daily dose of 6 mg/kg for MDR-MRSP pyoderma treatment when limited antibiotic options are available., (© 2021 ESVD and ACVD.)

The observation of beam spin asymmetries in two-pion production in semi-inclusive deep inelastic scattering off an unpolarized proton target is reported. The data presented here were taken in the fall of 2018 with the CLAS12 spectrometer using a 10.6 GeV longitudinally spin-polarized electron beam delivered by CEBAF at JLab. The measured asymmetries provide the first opportunity to extract the parton distribution function e(x), which provides information about the interaction between gluons and quarks, in a collinear framework that offers cleaner access than previous measurements. The asymmetries also constitute the first ever signal sensitive to the helicity-dependent two-pion fragmentation function G&#95;{1}^{⊥}. A clear sign change is observed around the ρ mass that appears in model calculations and is indicative of the dependence of the produced pions on the helicity of the fragmenting quark.

The quark structure of the f&#95;{2}(1270) meson has, for many years, been assumed to be a pure quark-antiquark (qq[over ¯]) resonance with quantum numbers J^{PC}=2^{++}. Recently, it was proposed that the f&#95;{2}(1270) is a molecular state made from the attractive interaction of two ρ mesons. Such a state would be expected to decay strongly to final states with charged pions due to the dominant decay ρ→π^{+}π^{-}, whereas decay to two neutral pions would likely be suppressed. Here, we measure for the first time the reaction γp→π^{0}π^{0}p, using the CEBAF Large Acceptance Spectrometer detector at Jefferson Lab for incident beam energies between 3.6 and 5.4 GeV. Differential cross sections, dσ/dt, for f&#95;{2}(1270) photoproduction are extracted with good precision due to low backgrounds and are compared to theoretical calculations.

In an emulsion-counter hybrid experiment performed at J-PARC, a Ξ^{-} absorption event was observed which decayed into twin single-Λ hypernuclei. Kinematic calculations enabled a unique identification of the reaction process as Ξ^{-}+^{14}N→&#95;{Λ}^{10}Be+&#95;{Λ}^{5}He. For the binding energy of the Ξ^{-} hyperon in the Ξ^{-}-^{14}N system a value of 1.27±0.21  MeV was deduced. The energy level of Ξ^{-} is likely a nuclear 1p state which indicates a weak ΞN-ΛΛ coupling.

A first measurement of the longitudinal beam spin asymmetry A&#95;{LU} in the semi-inclusive electroproduction of pairs of charged pions is reported. A&#95;{LU} is a higher-twist observable and offers the cleanest access to the nucleon twist-3 parton distribution function e(x). Data have been collected in the Hall-B at Jefferson Lab by impinging a 5.498-GeV electron beam on a liquid-hydrogen target, and reconstructing the scattered electron and the pion pair with the CLAS detector. One-dimensional projections of the A&#95;{LU}^{sinϕ&#95;{R}} moments are extracted for the kinematic variables of interest in the valence quark region. The understanding of dihadron production is essential for the interpretation of observables in single-hadron production in semi-inclusive DIS, and pioneering measurements of single-spin asymmetries in dihadron production open a new avenue in studies of QCD dynamics.

We have measured beam-spin asymmetries to extract the sinϕ moment A&#95;{LU}^{sinϕ} from the hard exclusive e[over →]p→e^{'}nπ^{+} reaction above the resonance region, for the first time with nearly full coverage from forward to backward angles in the center of mass. The A&#95;{LU}^{sinϕ} moment has been measured up to 6.6  GeV^{2} in -t, covering the kinematic regimes of generalized parton distributions (GPD) and baryon-to-meson transition distribution amplitudes (TDA) at the same time. The experimental results in very forward kinematics demonstrate the sensitivity to chiral-odd and chiral-even GPDs. In very backward kinematics where the TDA framework is applicable, we found A&#95;{LU}^{sinϕ} to be negative, while a sign change was observed near 90° in the center of mass. The unique results presented in this Letter will provide critical constraints to establish reaction mechanisms that can help to further develop the GPD and TDA frameworks.

Objective: To describe the Healthy Meal Program (HMP), a community-academic partnership that aims to address the food insecurity and social isolation in older adults living in an urban setting., Program Implementation: Low-income older adults were screened for food insecurity and social isolation. A partnership with the food bank and a farm-based organization helped provide a weekly congregate or home-delivered meal, pilot a cooking class, and offer a mobile market selling fresh vegetables at discounted prices., Program Evaluation: Overall, 339 individuals agreed to participate in the screening process. Sixty-eight percent (n = 230) screened positive for food insecurity and 41% (n = 139) screened positive for social isolation. Among individuals who were food insecure, 159 were referred to a food commodity program, 31 to meals on wheels, 23 to Supplemental Nutrition Assistance Program benefits, and 28 to emergency food pantries. The mobile market served 75 participants weekly and 15 individuals took part in cooking classes., Conclusions: Screening for food insecurity and social isolation in the HMP helped to assess the prevalence of these social determinants of health in low-income older adults. Weekly congregate meals, home visits, and group cooking classes were initiatives taken to decrease the impact of food insecurity and social isolation in this vulnerable population., (© 2020 Wiley Periodicals LLC.)

Background: Antiangiogenic-targeting agents have low response rates in patients with nonpancreatic neuroendocrine tumors (NETs). Nintedanib is an oral antiangiogenic agent that has inhibitory effects on the fibroblast growth factor receptor, which is highly expressed in NETs. The authors hypothesized that nintedanib would be active in patients with nonpancreatic NETs., Methods: Patients with advanced, grade 1 or 2, nonpancreatic NETs who were receiving a stable dose of somatostatin analogue were enrolled. Nintedanib was administered at a dose of 200 mg twice daily in 28-day cycles. The primary endpoint was progression-free survival (PFS) at 16 weeks., Results: Thirty-two patients were enrolled, and 30 were evaluable for the primary outcome. Most had radiographic disease progression within 12 months before enrollment. The 16-week PFS rate was 83%, and the median PFS and overall survival were 11.0 months and 32.7 months, respectively. Nintedanib was well tolerated and delayed deterioration in quality of life. The baseline serotonin level had a strong, positive correlation with activated but exhausted T cells., Conclusions: Nintedanib is active in nonpancreatic NETs. The immunosuppressive effect of serotonin should be targeted in future clinical trials., (© 2020 American Cancer Society.)

Background: Influenza is an infectious disease causing a high annual economic and public health burden. The most efficient management of the disease is through prevention with vaccination. Many influenza vaccines are available, with varying efficacy and cost, targeting different age groups. Therefore, strategic decision-making about which vaccine to deliver to whom is warranted to improve efficiency., Objective: We present the use of a constrained optimization (CO) model to evaluate targeted strategies for providing influenza vaccines in three adult age groups in the USA., Methods: CO was considered for identifying an influenza vaccine provision strategy that maximizes the benefits at constrained annual budgets, by prioritizing vaccines based on return on investment. The approach optimizes a set of predefined outcome measures over several years resulting from an increasing investment using the best combination of influenza vaccines., Results: Results indicate the importance of understanding the relative differences in benefits for each vaccine type within and across age groups. Scenario and threshold analyses demonstrate the impact of changing budget distribution over time, price setting per vaccine type, and selection of outcome measure to optimize., Conclusion: Significant gains in cost efficiency can be realized for a decision maker using a CO model, especially for a disease like influenza with many vaccine options. Testing the model under different scenarios offers powerful insights into maximum achievable benefit overall and per age group within the predefined constraints of a vaccine budget.

Supercharge end-to-side anterior interosseous-to-ulnar motor nerve transfer is commonly performed in the authors' institution to augment intrinsic hand function. Following observations of recovery patterns, the authors hypothesized that despite its more distal innervation, the first dorsal interosseous muscle recovers to a greater extent than the abductor digiti minimi muscle. The objective of this work was to evaluate the clinical and electrodiagnostic pattern of reinnervation of intrinsic hand musculature following supercharge end-to-side anterior interosseous-to-ulnar motor nerve transfer. A retrospective cohort of prospectively collected data included all patients who underwent a supercharge end-to-side anterior interosseous-to-ulnar motor nerve transfer. Two independent reviewers performed data collection. Reinnervation was assessed with two primary outcome measures: (1) clinically, with serial Medical Research Council strength assessments; and (2) electrodiagnostically, with serial motor amplitude measurements. Statistical analysis was performed using nonparametric statistics. Seventeen patients (65 percent male; mean age, 56.9 ± 13.3 years) were included with a mean follow-up of 16.7 ± 8.5 months. Preoperatively, all patients demonstrated clinically significant weakness and electrodiagnostic evidence of denervation. Postoperatively, strength and motor amplitude increased significantly for both the first dorsal interosseous muscle (p = 0.002 and p = 0.016) and the abductor digiti minimi muscle (p = 0.044 and p = 0.015). Despite comparable preoperative strength (p = 0.098), postoperatively, the first dorsal interosseous muscle achieved significantly greater strength when compared to the abductor digiti minimi muscle (p = 0.023). Following supercharge end-to-side anterior interosseous-to-ulnar motor nerve transfer, recovery of intrinsic muscle function differs between the abductor digiti minimi and the first dorsal interosseous muscles, with better recovery observed in the more distally innervated first dorsal interosseous muscle. Further work to elucidate the underlying physiologic and anatomical basis for this discrepancy is indicated. CLINICAL QUESTION/LEVEL OF EVIDENCE:: Therapeutic, IV.

Public health and other researchers express growing concern for the role of maternal adiposity and gestational weight gain in driving the obesity epidemic and health disparities based on race and class. Biocultural scholars must continue to contribute to conversations on how best to address issues of population health including the developmental context of obesity, drawing from both evolutionary and social theory. I discuss a number of intervention studies designed to address gestational weight gain in low-income and minority women and consider the degree to which they address the social, political, and economic context, and developmental history of mothers. I further examine the potential for these interventions, focused on the individual behavior of mothers, to contribute to stigma based on socially defined race, class, and body shape and size, and to draw attention away from the powerful economic interests that contribute to and benefit from the obesity epidemic. I end with a discussion of the value of developmental systems theory for thinking critically about obesity and other health interventions., (© 2019 Wiley Periodicals, Inc.)

Staphylococcus pseudintermedius is a Gram-positive bacterial species highly relevant to animal and human health. In this study, we report the draft genome sequences of two clinical isolates of S. pseudintermedius from canine skin biopsy specimens at the Dermatology Service of the Auburn University Small Animal Teaching Hospital., (Copyright © 2020 Cao et al.)

We measured missing mass spectrum of the ^{12}C(γ,p) reaction for the first time in coincidence with potential decay products from η^{'} bound nuclei. We tagged an (η+p) pair associated with the η^{'}N→ηN process in a nucleus. After applying kinematical selections to reduce backgrounds, no signal events were observed in the bound-state region. An upper limit of the signal cross section in the opening angle cosθ&#95;{lab}^{ηp}<-0.9 was obtained to be 2.2  nb/sr at the 90% confidence level. It is compared with theoretical cross sections, whose normalization ambiguity is suppressed by measuring a quasifree η^{'} production rate. Our results indicate a small branching fraction of the η^{'}N→ηN process and/or a shallow η^{'}-nucleus potential.

Study Design: This is a case report., Introduction: Persons with rheumatoid arthritis frequently use assistive devices as a compensatory strategy to enhance occupational performance when client factors such as hand weakness, pain, and/or limited range of motion interfere with activity performance. Computer-aided design software and 3D printers are increasingly being used to design and make assistive devices., Purpose of the Study: This case report describes a client-centered approach in the selection, three-dimensional (3D) printing, and evaluation of outcomes for three assistive devices to enhance occupational performance in a subject with rheumatoid arthritis., Methods: Outcome measures used in this study included the Patient-Specific Functional Scale, Numeric Pain Rating Scale, and Quebec User Evaluation of Satisfaction with Assistive Technology V2.0. Activity analysis along with the subject input informed a client-centered approach in the selection, color, and design modifications of 3D printed assistive devices made for the study., Results: The subject reported decreased pain, improved occupational performance, and satisfaction with use of 3D printed assistive devices to open plastic beverage bottles, unlock/lock doors, and write., Discussion: 3D printing offers therapists a means to design and make assistive devices that can be cost-effective, customizable, and client-centered., Conclusion: Assistive devices made with 3D printing resulted in positive outcomes in a subject with rheumatoid arthritis., (Copyright © 2020 Hanley & Belfus. Published by Elsevier Inc. All rights reserved.)

Objectives: The objectives of this pilot study were to analyze the electromyography (EMG) activity of masseter and anterior temporalis muscles during chewing in 2 different posture conditions: natural head posture (NHP) and maximum yet comfortable forward head posture (FHP) in healthy individuals; and to compare EMG activity between subjects based on their NHP during chewing., Methods: Fifteen subjects participated. Sagittal head posture in sitting position was clinically assessed using a plumb line. Participants were classified as having FHP or upright head posture (UP). Surface EMG was used to evaluate superficial masseter and anterior temporalis bilaterally during chewing in NHP and FHP. Three trials with five chewing cycles were recorded. EMG data were normalized using a maximum voluntary contraction. An independent t -test was used to calculate differences between sides. If no differences were found, both sides were analyzed together. To analyze differences between the 2 conditions, a paired t -test was used. Independent t -test was used to calculate difference between subjects with UP and FHP., Results: A significant increase in muscle activity was found for masseter muscle in the FHP condition. No differences were found in muscle activity in natural head position by posture classification. A trend of increased activity was observed for masseter and temporalis muscles during chewing in FHP., Conclusion: Head and neck posture was found to influence masticatory muscle activity during the function of chewing. The results of this study may help clinicians to better understand the association between head and neck posture alterations with masticatory muscles related disorders., Competing Interests: The authors report no conflicts of interest., (© 2020 Craniofacial Research Foundation. Published by Elsevier B.V. All rights reserved.)

Precision health's more individualized molecular approach will enrich our understanding of disease etiology and patient outcomes. Universal implementation of precision health will not be feasible, however, until there is much greater automation of processes related to genomic data transmission, transformation, and interpretation. In this paper, we describe a framework for genomic data flow developed by the Clinical Informatics Work Group of the NIH National Human Genome Research Institute (NHGRI) IGNITE Network consortium. We subsequently report the results of a genomic data flow survey administered to sites funded by NIH-NHGRI for large scale genomic medicine implementations. Finally, we discuss insights and challenges identified through these survey results as they relate to both the current and a desirable future state of genomic data flow., (©2019 AMIA - All rights reserved.)

The ability to isolate adult cardiac myocytes has permitted researchers to study a variety of cardiac pathologies at the single cell level. While advances in calcium sensitive dyes have permitted the robust optical recording of single cell calcium dynamics, recording of robust transmembrane optical voltage signals has remained difficult. Arguably, this is because of the low single to noise ratio, phototoxicity, and photobleaching of traditional potentiometric dyes. Therefore, single cell voltage measurements have long been confined to the patch clamp technique which while the gold standard, is technically demanding and low throughput. However, with the development of novel potentiometric dyes, large, fast optical responses to changes in voltage can be obtained with little to no phototoxicity and photobleaching. This protocol describes in detail how to isolate adult murine myocytes which can be used for cellular shortening, calcium, and optical voltage measurements. Specifically, the protocol describes how to use a ratiometric calcium dye, a single-excitation calcium dye, and a single excitation voltage dye. This approach can be used to assess the cardiotoxicity and arrhythmogenicity of various chemical agents. While phototoxicity is still an issue at the single cell level, methodology is discussed on how to reduce it.

Current work investigates a typical issue in formulating a physically stable solution especially when more than one counter ions exist in the composition. The impact of different counter ions on solubilization of monohydrate esylate salt of a free base GSK-497,[BH + :C 2 H 5 SO 3 - :H 2 O] (1:1) (pKa value 8.0) was investigated to formulate ready to use small volume injectable solution. The concentration dependent aggregation was also appeared to be responsible for hemolytic nature of the drug, therefore a careful investigation was needed to select appropriate counter ion solution without compromising solubilization and leading into higher order aggregation. The esylate salt's native pH in water was closer to pH max , thus it was risky to render the solution unbuffered. Generally, it is recommended to formulate at least two pH unit away from pH max , using a lactate counter ion (other than esylate salt of API salt) that did not compromise solubility of the given phase and did not appear to promote higher order of aggregation. The rationale for selecting second counter ion was primarily based on the comparison of esylate salt's solubility product (K max ), with the K sp value generated from equilibrium solubility of the free base combined with several different counter ions (chloride, lactate, aspartate, citrate and tartrate) at equimolar molar ratio. This approach suggested that the use of a counter ion with higher K sp (lactate and aspartate) value did not compromise the solubility of original esylate salt but a higher extent of aggregation was possible if aspartate is used to achieve higher solubility. In contrary, use of a counter ion with lower K sp (citrate, tartrate, chloride) reduced the solubility hence did not favor higher order of aggregation. Thus, based on K sp (citrate, tartrate, chloride) reduced the solubility hence did not favor higher order of aggregation. Thus, based on K sp comparison a rationale of selecting second counter ion to buffer the salt solution is discussed in this work and optimal formulation concentration is determined based on drug aggregation threshold in solution., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Aims: Morphine is shown to relieve chronic breathlessness in chronic obstructive pulmonary disease. There are no definitive data in people with heart failure. We aimed to determine the effectiveness and cost-effectiveness of 12 weeks morphine therapy for the relief of chronic breathlessness in people with chronic heart failure compared with placebo., Methods and Results: Parallel group, double-blind, randomized, placebo-controlled, phase III trial of 20 mg daily oral modified release morphine was conducted in 13 sites in England and Scotland: hospital/community cardiology or palliative care outpatients. The primary analysis compared between-group numerical rating scale average breathlessness/24 hours at week 4 using a covariance pattern linear mixed model. Secondary outcomes included treatment-emergent harms (worse or new). The trial closed early due to slow recruitment, randomizing 45 participants [average age 72 (range 39-89) years; 84% men; 98% New York Heart Association class III]. For the primary analysis, the adjusted mean difference was 0.26 (95% confidence interval, -0.86 to 1.37) in favour of placebo. All other breathlessness measures improved in both groups (week 4 change-from-baseline) but by more in those assigned to morphine. Neither group was excessively drowsy at baseline or week 4. There were no between-group differences in quality of life (Kansas) or cognition (Montreal) at any time point. There was no exercise-related desaturation and no change between baseline and week 4 in either group. There was no change in vital signs at week 4. The natriuretic peptide measures fell in both groups but by more in the morphine group [morphine 2169 (1092, 3851) pg/mL vs. placebo 2851 (1694, 5437)] pg/mL. There was no excess serious adverse events in the morphine group. Treatment-emergent harms during the first week were more common in the morphine group; all apart from 1 were ≤ grade 2., Conclusions: We could not answer our primary objectives due to inadequate power. However, we provide novel placebo-controlled medium-term benefit and safety data useful for clinical practice and future trial design. Morphine should only be prescribed in this population when other measures are unhelpful and with early management of side effects., (© 2019 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.)

Objective: This study describes secular trends in physical stature, Cormic Index (CI), and body mass index (BMI) of adult Makushi Amerindians born between 1910 and 1980, compares the stature of these Makushi adults to Makushi adults measured in 1921, and provides contextual data to inform the findings., Methods: Pearson's correlation was used to assess the relationship between year of birth and physical stature, BMI, and CI for 231 females and 113 males, 20 to 90 years of age measured in 2000 to 2001. Wilcoxon's test was used to compare physical stature of Makushi adults measured in 2000 to 2001 with that of 40 Makushi adults measured in 1921., Results: Among Makushi measured in 2000 to 2001, females and males born more recently were taller and had a lower CI but did not differ in BMI relative to their elders. Makushi measured in 2000 to 2001 are significantly taller than those Maksuhi measured in 1921., Conclusion: The increased physical stature of and decreased CI in more recently born Makushi may be explained by a more favorable early life environment possibly due to public health measures and dietary changes. As well, trends in stature may be linked to genetic admixture with African-Guyanese migrating into the region during this time., (© 2019 Wiley Periodicals, Inc.)

The eyes and periorbital region are central components of facial beauty and harmony, but the periorbital region is also one of the earliest to show signs of aging. Over the past few decades, significant progress has been made in our understanding of the anatomy in this area, as well as the deleterious effects of aging in this region. In turn, surgical philosophy and techniques have evolved to better combat changes in this area to achieve a more youthful, natural appearance., Competing Interests: None., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Knowledge of optical properties, such as the refractive index (RI), of biological tissues is important in optical imaging, as they influence the distribution and propagation of light in tissue. To accurately study the response of cancerous cells to drugs, optimised imaging protocols are required. This study uses a simple custom-built spectral domain optical coherence tomography (OCT) system to conduct RI measurements of multicellular spheroids, three-dimensional (3D) in-vitro culture systems, of the cell line HCT116. The spheroid RIs are compared to study the effect of growth over time. To improve confocal microscopy imaging protocols, two immersion media (glycerol and ScaleView-A2) matching the spheroid RIs were trialled, with the aim to reduce the RI mismatch between the spheroid and the immersion medium and thus improve imaging depth with confocal microscopy. ScaleView-A2 (n = 1.380) aided in achieving greater depths of imaging of the multicellular spheroids under confocal microscopy. This improvement in imaging depth confirmed the utility of our RI measurements, proving the promising outlook of OCT as a complementary tool to microscopy in cancer research.

In the past two decades, deeply virtual Compton scattering of electrons has been successfully used to advance our knowledge of the partonic structure of the free proton and investigate correlations between the transverse position and the longitudinal momentum of quarks inside the nucleon. Meanwhile, the structure of bound nucleons in nuclei has been studied in inclusive deep-inelastic lepton scattering experiments off nuclear targets, showing a significant difference in longitudinal momentum distribution of quarks inside the bound nucleon, known as the EMC effect. In this Letter, we report the first beam spin asymmetry (BSA) measurement of exclusive deeply virtual Compton scattering off a proton bound in ^{4}He. The data used here were accumulated using a 6 GeV longitudinally polarized electron beam incident on a pressurized ^{4}He gaseous target placed within the CLAS spectrometer in Hall-B at the Thomas Jefferson National Accelerator Facility. The azimuthal angle (ϕ) dependence of the BSA was studied in a wide range of virtual photon and scattered proton kinematics. The Q^{2}, x&#95;{B}, and t dependencies of the BSA on the bound proton are compared with those on the free proton. In the whole kinematical region of our measurements, the BSA on the bound proton is smaller by 20% to 40%, indicating possible medium modification of its partonic structure.