Underrepresentation of racial and ethnic minority groups in gynecologic oncology: An analysis of over 250 trials.

OBJECTIVE: To describe the participation of racial and ethnic minority groups (REMGs) in gynecologic oncology trials. METHODS: Gynecologic oncology studies registered on ClinicalTrials.gov between 2007 and 2020 were identified. Trials with published results were analyzed based on reporting of race/ethnicity in relation to disease site and trial characteristics. Expected enrollment by race/ethnicity was calculated and compared to actual enrollment, adjusted for 2010 US Census population data. RESULTS: 2146 gynecologic oncology trials were identified. Of published trials (n = 252), 99 (39.3%) reported race/ethnicity data. Recent trials were more likely to report these data (36% from 2007 to 2009; 51% 2013-2015; and 53% from 2016 to 2018, p = 0.01). Of all trials, ovarian cancer trials were least likely to report race/ethnicity data (32.1% vs 39.3%, p = 0.011). Population-adjusted under-enrollment for Blacks was 7-fold in ovarian cancer, Latinx 10-fold for ovarian and 6-fold in uterine cancer trials, Asians 2.5-fold in uterine cancer trials, and American Indian and Alaska Native individuals 6-fold in ovarian trials. Trials for most disease sites have enrolled more REMGs in recent years - REMGs made up 19.6% of trial participants in 2007-2009 compared to 38.1% in 2016-2018 (p < 0.0001). CONCLUSION: Less than half of trials that published results reported race/ethnicity data. Available data reveals that enrollment of REMGs is significantly below expected rates based on national census data. These disparities persisted even after additionally adjusting for population size. Despite improvement in recent years, additional recruitment of REMGs is needed to achieve more representative and equitable participation in gynecologic cancer clinical trials.

Patient medication management, understanding and adherence during the transition from hospital to outpatient care - a qualitative longitudinal study in polymorbid patients with type 2 diabetes.

BACKGROUND: Continuity of care is under great pressure during the transition from hospital to outpatient care. Medication changes during hospitalization may be poorly communicated and understood, compromising patient safety during the transition from hospital to home. The main aims of this study were to investigate the perspectives of patients with type 2 diabetes and multimorbidities on their medications from hospital discharge to outpatient care, and their healthcare journey through the outpatient healthcare system. In this article, we present the results focusing on patients' perspectives of their medications from hospital to two months after discharge. METHODS: Patients with type 2 diabetes, with at least two comorbidities and who returned home after discharge, were recruited during their hospitalization. A descriptive qualitative longitudinal research approach was adopted, with four in-depth semi-structured interviews per participant over a period of two months after discharge. Interviews were based on semi-structured guides, transcribed verbatim, and a thematic analysis was conducted. RESULTS: Twenty-one participants were included from October 2020 to July 2021. Seventy-five interviews were conducted. Three main themes were identified: (A) Medication management, (B) Medication understanding, and (C) Medication adherence, during three periods: (1) Hospitalization, (2) Care transition, and (3) Outpatient care. Participants had varying levels of need for medication information and involvement in medication management during hospitalization and in outpatient care. The transition from hospital to autonomous medication management was difficult for most participants, who quickly returned to their routines with some participants experiencing difficulties in medication adherence. CONCLUSIONS: The transition from hospital to outpatient care is a challenging process during which discharged patients are vulnerable and are willing to take steps to better manage, understand, and adhere to their medications. The resulting tension between patients' difficulties with their medications and lack of standardized healthcare support calls for interprofessional guidelines to better address patients' needs, increase their safety, and standardize physicians', pharmacists', and nurses' roles and responsibilities.

Navigating outpatient care of patients with type 2 diabetes after hospital discharge - a qualitative longitudinal study.

BACKGROUND: The transition from hospital to outpatient care is a particularly vulnerable period for patients as they move from regular health monitoring to self-management. This study aimed to map and investigate the journey of patients with polymorbidities, including type 2 diabetes (T2D), in the 2 months following hospital discharge and examine patients' encounters with healthcare professionals (HCPs). METHODS: Patients discharged with T2D and at least two other comorbidities were recruited during hospitalization. This qualitative longitudinal study consisted of four semi-structured interviews per participant conducted from discharge up to 2 months after discharge. The interviews were based on a guide, transcribed verbatim, and thematically analyzed. Patient journeys through the healthcare system were represented using the patient journey mapping methodology. RESULTS: Seventy-five interviews with 21 participants were conducted from October 2020 to July 2021. The participants had a median of 11 encounters (min-max: 6-28) with HCPs. The patient journey was categorized into six key steps: hospitalization, discharge, dispensing prescribed medications by the community pharmacist, follow-up calls, the first medical appointment, and outpatient care. CONCLUSIONS: The outpatient journey in the 2 months following discharge is a complex and adaptive process. Despite the active role of numerous HCPs, navigation in outpatient care after discharge relies heavily on the involvement and responsibilities of patients. Preparation for discharge, post-hospitalization follow-up, and the first visit to the pharmacy and general practitioner are key moments for carefully considering patient care. Our findings underline the need for clarified roles and a standardized approach to discharge planning and post-discharge care in partnership with patients, family caregivers, and all stakeholders involved.

Large-scale, mobile and technology-enhanced serious game for interprofessional education: pilot study and lessons learnt.

Recent research suggests that serious gaming is a promising strategy for interprofessional education (IPE). This report describes the design and pilot testing of a large-scale, mobile, technology-enhanced serious game embedded in the IPE curriculum in Geneva, Switzerland. Organized into teams of eight, the students were tasked with finding a young patient who had just escaped from the intensive care unit. Through a series of 10 stations, they explored hospital- and community-based locations of the healthcare system and were engaged in various learning and game activities; they were rewarded with cues to unveil the mystery. A total of 582 undergraduate students from seven disciplines (medicine, midwifery, nursing, nutrition-dietetics, pharmacy, physiotherapy, and technology in medical radiology) took part. Survey results (response rate: 62.8%) suggest that an overall majority of students valued the game, particularly the collaborative experience of actively learning from others in autonomous teams. Qualitative feedback allowed us to identify future areas for improvement: simplifying the adventure storyline and optimizing student flow. Educational institutions across the world facing challenges when creating IPE activities will find in this report ideas and lessons learnt to use mobile technology and serious gaming for large cohorts of students.

Estimation of adherence to medication treatment in presence of censoring.

AIMS: The purpose of this study is to provide a theoretical framework for the analysis of medication adherence based on longitudinal data from electronic medication monitors and to suggest methods for unbiased estimation of the effect of time and covariates on adherence. METHODS: After defining the statistical summaries involved in adherence analyses and the assumptions necessary for their estimation, we address the issue of bias encountered when adherence is estimated on censored data. We suggest 2 unbiased methods to estimate adherence: (i) indirect combining implementation and persistence; and (ii) based on weights, allowing estimation of the effect of time and covariates on adherence via generalized estimating equations models. RESULTS: We applied the proposed methods to investigate the effect of sex on adherence in a sample of 43 oncology patients followed 1 year. Implementation was higher for men than for women at baseline (98.8 vs. 97.5%, odds ratio [OR] 2.08, 95% confidence interval [CI]: 1.00-4.35), whereas the relationship was reversed at 1 year (94.5 vs. 96.4%, OR 0.65, 95%CI: 0.28-1.52). Adherence declined faster in men, with year-end values of 46.3% for men and 92.2% for women (OR 0.07, 95%CI: 0.02-0.26). CONCLUSION: Estimation of adherence is a complex statistical issue with longitudinal and duration data, possibly censored, interleaving. This study provides a theoretical framework and suggests methods for unbiased estimation of adherence as a function of time and covariates. This allows the effect of an intervention to be estimated in clinical trials, and helps healthcare providers reframe adherence programmes to address covariates such as sex.

The effect of phacoemulsification on visual function among Filipino cataract patients measured by a validated Filipino translation of Catquest-9SF.

BACKGROUND: This study developed a validated Filipino version of the Catquest-9SF and administered it to cataract patients pre- and post- surgery. METHODS: This is a two-phase, single-center, cross sectional, questionnaire type study. The study included participants decked for surgery who are 18 years and above. Sampling was done purposively. The Catquest-9SF questionnaire was translated into Filipino, according to a standard procedure, and validated. The validated version was administered to the participants before and after unilateral cataract surgery. Data were analyzed using Rasch analysis. RESULTS: Sixty-one patients were enrolled in the study. The preliminary Rasch analysis showed misfit of item 2, which was subsequently excluded from analysis. The remaining eight items showed person separation index of 2.70, reliability coefficient of 0.88, infit of 0.66 to 1.17, outfit of 0.66 to 1.49, observed raw variance explained by measures of 55.3% and eigenvalues of 1.9, 1.4, 1.2, 1.0 and 0.9. There was slightly poor targeting (mean person location 1.24) and multidimensionality but no evidence of differential item functioning (DIF). High internal consistency of items were observed (Cronbach's alpha ≥ 90). Comparison of responses between pre- and post-surgery showed highly significant marginal homogeneity (p < 0.001). CONCLUSION: The Filipino translation of Catquest-9SF, the Catquest-8SF-PH, was highly valid. It showed improved perceived visual outcomes among Filipino patients post-cataract surgery.

Effectiveness of the multi-component intervention 'Focus' on reducing smoking among students in the vocational education setting: a cluster randomized controlled trial.

BACKGROUND: Social inequality in smoking remains an important public health issue. Upper secondary schools offering vocational education and training (VET) comprise more students from lower socioeconomic backgrounds and have higher smoking prevalence than general high schools. This study examined the effects of a school-based multi-component intervention on students' smoking. METHODS: A cluster randomized controlled trial. Eligible participants were schools offering VET basic courses or preparatory basic education in Denmark, and their students. Schools were stratified by subject area and eight schools were randomly allocated to intervention (1,160 invited students; 844 analyzed) and six schools to control (1,093 invited students; 815 analyzed). The intervention program comprised smoke-free school hours, class-based activities, and access to smoking cessation support. The control group was encouraged to continue with normal practice. Primary outcomes were daily cigarette consumption and daily smoking status at student level. Secondary outcomes were determinants expected to impact smoking behavior. Outcomes were assessed in students at five-month follow-up. Analyses were by intention-to-treat and per protocol (i.e., whether the intervention was delivered as intended), adjusted for covariates measured at baseline. Moreover, subgroup analyses defined by school type, gender, age, and smoking status at baseline were performed. Multilevel regression models were used to account for the cluster design. Missing data were imputed using multiple imputations. Participants and the research team were not blinded to allocation. RESULTS: Intention-to-treat analyses showed no intervention effect on daily cigarette consumption and daily smoking. Pre-planned subgroup analyses showed statistically significant reduction in daily smoking among girls compared with their counterparts in the control group (OR = 0.39, 95% CI: 0.16, 0.98). Per-protocol analysis suggested that schools with full intervention had higher benefits compared with the control group (daily smoking: OR = 0.44, 95% CI: 0.19, 1.02), while no marked differences were seen among schools with partial intervention. CONCLUSION: This study was among the first to test whether a complex, multicomponent intervention could reduce smoking in schools with high smoking risk. Results showed no overall effects. There is a great need to develop programs for this target group and it is important that they are fully implemented if an effect is to be achieved. TRIAL REGISTRATION: https://www.isrctn.com/ISRCTN16455577 , date of registration 14/06/2018.

Infant negative affectivity and patterns of affect-biased attention.

Biased attention toward affective cues often cooccurs with the emergence and maintenance of internalizing disorders. However, few studies have assessed whether affect-biased attention in infancy relates to early indicators of psychopathological risk, such as negative affectivity. The current study evaluates whether negative affectivity relates to affect-biased attention in 6-month-old infants. Affect-biased attention was assessed via a free-viewing eye-tracking task in which infants were presented with a series of face pairs (comprised of a happy, angry, or sad face and a neutral face). Attention was quantified with metrics of both attention orienting and attention holding. Overall, infants showed no differences in attention orienting (i.e., speed of looking) or attention holding (i.e., duration of looking) toward emotional faces in comparison to the neutral face pairs. Negative affectivity, assessed via parent report, did not relate to attention orienting but was associated with biased attention toward positive, happy faces and away from threat-cueing, angry faces in comparison to the neutral faces they were paired with. These findings suggest that negative affectivity is associated with differences in attention holding, but not initial orienting toward emotional faces; biases which have important implications for the trajectory of socioemotional development.

Predictors of Preexposure Prophylaxis Eligibility among Pregnant People with Opioid Use Disorder.

OBJECTIVE: We seek to evaluate risk factors for eligibility for preexposure prophylaxis (PrEP) among pregnant people with opioid use disorder (OUD). STUDY DESIGN: This is a single-site retrospective cohort study of pregnant people admitted for management of OUD at an urban, tertiary care center from 2013 to 2022. PrEP eligibility was defined based on (1) modified American College of Obstetricians and Gynecologists' (ACOG) 2014 criteria: diagnosis of a sexually transmitted infection (STI), engagement in transactional sex work, intravenous drug use (IVDU), or incarceration and (2) modified 2021 Centers for Disease Control (CDC) criteria: diagnosis of bacterial STI (e.g., gonorrhea or syphilis) or transactional sex work. Risk factors associated with PrEP eligibility were evaluated using chi- square or Fischer's exact tests for categorical variables and t-tests or Wilcoxon rank-sum tests for continuous variables. Multivariable regression was used to control for confounding covariates, defined as p < 0.10 on bivariate analysis. p < 0.05 was used to indicate statistical significance. RESULTS: A total of 132 individuals met inclusion criteria, of whom 101 (76.5%) were deemed eligible for PrEP by meeting one or more modified 2014 ACOG criteria: 42 (31.8%) were incarcerated or had one or more STIs, while 30 (22.7%) endorsed engaging in transactional sex work and 68 (58.6%) endorsed IVDU. Using modified 2021 CDC criteria, 37 (28%) met PrEP eligibility, with 12 (9.1%) diagnosed specifically with a bacterial STI and 30 (22.7%) engaging in transactional sex work. Only comorbid psychiatric illness was associated with an increased risk for PrEP eligibility based on 2014 criteria, which persisted after controlling for maternal race/ethnicity (aRR 1.52, 95% confidence interval [CI] 1.24-1.86), and 2021 criteria, which persisted after controlling for nulliparity (aRR 2.12, 95% CI 1.30-3.57). CONCLUSION: A significant number of pregnant people with OUD meet one or more criteria for PrEP, with comorbid psychiatric conditions increasing the risk of meeting criteria. KEY POINTS: · Comorbid psychiatric illness is significantly associated with high risk of PrEP eligibility.. · A large proportion of pregnant individuals with active OUD meet criteria for PrEP prescribing.. · Risk-based screening algorithms for PrEP eligibility have limitations..

Nucleation of α-Synuclein Amyloid Fibrils Induced by Cross-Interaction with ß-Hairpin Peptides Derived from Immunoglobulin Light Chains.

Heterologous interactions between different amyloid-forming proteins, also called cross-interactions, may have a critical impact on disease-related amyloid formation. ß-hairpin conformers of amyloid-forming proteins have been shown to affect homologous interactions in the amyloid self-assembly process. Here, we applied two ß-hairpin-forming peptides derived from immunoglobulin light chains as models to test how heterologous ß-hairpins modulate the fibril formation of Parkinson's disease-associated protein α-synuclein (αSyn). The peptides SMAhp and LENhp comprise ß-strands C and C' of the κ4 antibodies SMA and LEN, which are associated with light chain amyloidosis and multiple myeloma, respectively. SMAhp and LENhp bind with high affinity to the ß-hairpin-binding protein ß-wrapin AS10 according to isothermal titration calorimetry and NMR spectroscopy. The addition of SMAhp and LENhp affects the kinetics of αSyn aggregation monitored by Thioflavin T (ThT) fluorescence, with the effect depending on assay conditions, salt concentration, and the applied ß-hairpin peptide. In the absence of agitation, substoichiometric concentrations of the hairpin peptides strongly reduce the lag time of αSyn aggregation, suggesting that they support the nucleation of αSyn amyloid fibrils. The effect is also observed for the aggregation of αSyn fragments lacking the N-terminus or the C-terminus, indicating that the promotion of nucleation involves the interaction of hairpin peptides with the hydrophobic non-amyloid-ß component (NAC) region.

Kimura Disease: A case report with bilateral upper lid masses and a right parotid mass.

A 38-year-old male presented with bilateral upper eyelid masses and a right parotid mass. Nineteen years before the consultation, the patient experienced swelling at both upper eyelids. Formerly diagnosed by an ophthalmologist, corticosteroid, an anti-inflammatory medication, was prescribed for the patient, which resulted in partial resolution of the lid swelling. However, he was lost to follow-up, and progressive enlargement of the lids was observed with the development of a right parotid mass. The visual acuity of the patient was classified as counting fingers, three feet bilaterally. A detailed examination was difficult owing to the obstructive nature of the masses. However, ocular structures appeared intact. An excisional biopsy with a reconstruction of bilateral upper lids was performed. Histopathologic findings revealed a lymphoproliferative lesion suggestive of Kimura disease (KD). The patient was subsequently referred to rheumatology for management, where they started a regimen of oral steroids and antihistamines.

Leveraging PEPFAR-Supported Health Information Systems for COVID-19 Pandemic Response.

Since 2003, the US President's Emergency Plan for AIDS Relief (PEPFAR) has supported implementation and maintenance of health information systems for HIV/AIDS and related diseases, such as tuberculosis, in numerous countries. As the COVID-19 pandemic emerged, several countries conducted rapid assessments and enhanced existing PEPFAR-funded HIV and national health information systems to support COVID-19 surveillance data collection, analysis, visualization, and reporting needs. We describe efforts at the US Centers for Disease Control and Prevention (CDC) headquarters in Atlanta, Georgia, USA, and CDC country offices that enhanced existing health information systems in support COVID-19 pandemic response. We describe CDC activities in Haiti as an illustration of efforts in PEPFAR countries. We also describe how investments used to establish and maintain standards-based health information systems in resource-constrained settings can have positive effects on health systems beyond their original scope.

Management of Pathogenic CDH1 Variant Carriers Within the FREGAT Network: A Multicentric Retrospective Study.

OBJECTIVE: To describe the management of pathogenic CDH1 variant carriers (pCDH1vc) within the FREGAT (FRench Eso-GAsTric tumor) network. Primary objective focused on clinical outcomes and pathological findings, Secondary objective was to identify risk factor predicting postoperative morbidity (POM). BACKGROUND: Prophylactic total gastrectomy (PTG) remains the recommended option for gastric cancer risk management in pCDH1vc with, however, endoscopic surveillance as an alternative. METHODS: A retrospective observational multicenter study was carried out between 2003 and 2021. Data were reported as median (interquartile range) or as counts (proportion). Usual tests were used for univariate analysis. Risk factors of overall and severe POM (ie, Clavien-Dindo grade 3 or more) were identified with a binary logistic regression. RESULTS: A total of 99 patients including 14 index cases were reported from 11 centers. Median survival among index cases was 12.0 (7.6-16.4) months with most of them having peritoneal carcinomatosis at diagnosis (71.4%). Among the remaining 85 patients, 77 underwent a PTG [median age=34.6 (23.7-46.2), American Society of Anesthesiologists score 1: 75%] mostly via a minimally invasive approach (51.9%). POM rate was 37.7% including 20.8% of severe POM, with age 40 years and above and low-volume centers as predictors ( P =0.030 and 0.038). After PTG, the cancer rate on specimen was 54.5% (n=42, all pT1a) of which 59.5% had no cancer detected on preoperative endoscopy (n=25). CONCLUSIONS: Among pCDH1vc, index cases carry a dismal prognosis. The risk of cancer among patients undergoing PTG remained high and unpredictable and has to be balanced with the morbidity and functional consequence of PTG.

Music in premature infants enhances high-level cognitive brain networks.

Neonatal intensive care units are willing to apply environmental enrichment via music for preterm newborns. However, no evidence of an effect of music on preterm brain development has been reported to date. Using resting-state fMRI, we characterized a circuitry of interest consisting of three network modules interconnected by the salience network that displays reduced network coupling in preterm compared with full-term newborns. Interestingly, preterm infants exposed to music in the neonatal intensive care units have significantly increased coupling between brain networks previously shown to be decreased in premature infants: the salience network with the superior frontal, auditory, and sensorimotor networks, and the salience network with the thalamus and precuneus networks. Therefore, music exposure leads to functional brain architectures that are more similar to those of full-term newborns, providing evidence for a beneficial effect of music on the preterm brain.

The Hepatitis C Clinical Exchange Network: A Local Health Department Partnership With Acute Care Hospitals to Promote Screening and Treatment of Hepatitis C Virus Infection.

CONTEXT: As of 2015, an estimated 116000 New York City (NYC) residents had chronic hepatitis C, many of them undiagnosed. Although effective medications have been available since 2014 with the advent of direct-acting antivirals, provider-based barriers to treatment remain. The NYC Department of Health and Mental Hygiene (Health Department) coordinated the Hepatitis C Clinical Exchange Network (HepCX) from 2015 to 2019. The main goal of HepCX was to promote hepatitis C screening and treatment by hospital-based providers. PROGRAM: The Health Department recruited hepatitis C champions (Champions) from acute care hospitals (n = 40) to promote improved hepatitis C care at their institutions. The Health Department provided technical assistance for hospitals to improve electronic medical record (EMR) systems and implement reflex RNA testing, coordinated trainings to increase capacity to treat hepatitis C, and distributed dashboards containing facility-specific testing and treatment metrics. IMPLEMENTATION: By the end of the project period (2019), most hospitals (36/40; 90%) reported having a screening alert for baby boomers in their EMR system and 34 (85%) reported performing reflex RNA testing after a positive hepatitis C antibody test. The Health Department coordinated opportunities for Champions to share their work with providers from network hospitals at meetings and webinars and provided clinical education on hepatitis C treatment in partnership with a local nonprofit organization focused on liver health. Facility-specific dashboards were distributed annually to hospital leadership. RNA confirmation testing increased from an average of 57% in 2015 to 85% in 2018. Treatment initiation rates remained similar over 2 years, averaging 39% in 2017 and 38% in 2018. DISCUSSION: HepCX was a multipronged initiative designed to promote hepatitis C testing and treatment initiation among providers at NYC acute care hospitals. Improvements were observed in confirmatory testing rates; however, treatment initiation rates did not change. Further efforts should be targeted to hospitals in need of additional resources for linkage to care and treatment of hepatitis C.

The Inspired Life Program: Development of a multicomponent positive psychology intervention for rural adults in Ghana.

Although several theories and studies have explored human strengths and mental well-being at the global level, these insights are rarely tested and translated into practice in sub-Saharan Africa. This study aims to describe the development of a 10-session multicomponent positive psychology intervention, the Inspired Life Program (ILP), designed to promote mental health and reduce symptoms of depression and negative affect in rural adults in Ghana. Guided by the Medical Research Council's framework for developing complex interventions, a seven-step iterative community-based participatory research approach was adopted to develop the ILP, based on constructs and principles of positive psychology and cognitive-behavioral model. The final intervention components included a 10-session, two-hourly, once-weekly manualized program designed to promote meaningful and purposeful living, self-acceptance, personal growth, goal-setting and problem-solving skills, and positive thinking through group discussion and activity sessions. We describe the program theory and implementation strategy of the final intervention, and reflect on the challenges and lessons learned from applying this framework in the study context. The development of strengths-based interventions and practicality of methods to promote positive mental health in rural adults are feasible, and have important policy implications for mental health and social care in sub-Saharan Africa.

The development of the dorsal mesentery in human embryos and fetuses.

The vertebrate intestine has a continuous dorsal mesentery between pharynx and anus that facilitates intestinal mobility. Based on width and fate the dorsal mesentery can be subdivided into that of the caudal foregut, midgut, and hindgut. The dorsal mesentery of stomach and duodenum is wide and topographically complex due to strong and asymmetric growth of the stomach. The associated formation of the lesser sac partitions the dorsal mesentery into the right-sided "caval fold" that serves as conduit for the inferior caval vein and the left-sided mesogastrium. The thin dorsal mesentery of the midgut originates between the base of the superior and inferior mesenteric arteries, and follows the transient increase in intestinal growth that results in small-intestinal looping, intestinal herniation and, subsequently, return. The following fixation of a large portion of the abdominal dorsal mesentery to the dorsal peritoneal wall by adhesion and fusion is only seen in primates and is often incomplete. Adhesion and fusion of mesothelial surfaces in the lesser pelvis results in the formation of the "mesorectum". Whether Toldt's and Denonvilliers' "fasciae of fusion" identify the location of the original mesothelial surfaces or, alternatively, represent the effects of postnatal wear and tear due to intestinal motility and intra-abdominal pressure changes, remains to be shown. "Malrotations" are characterized by growth defects of the intestinal loops with an ischemic origin and a narrow mesenteric root due to insufficient adhesion and fusion.

The hydrophobic effect characterises the thermodynamic signature of amyloid fibril growth.

Many proteins have the potential to aggregate into amyloid fibrils, protein polymers associated with a wide range of human disorders such as Alzheimer's and Parkinson's disease. The thermodynamic stability of amyloid fibrils, in contrast to that of folded proteins, is not well understood: the balance between entropic and enthalpic terms, including the chain entropy and the hydrophobic effect, are poorly characterised. Using a combination of theory, in vitro experiments, simulations of a coarse-grained protein model and meta-data analysis, we delineate the enthalpic and entropic contributions that dominate amyloid fibril elongation. Our prediction of a characteristic temperature-dependent enthalpic signature is confirmed by the performed calorimetric experiments and a meta-analysis over published data. From these results we are able to define the necessary conditions to observe cold denaturation of amyloid fibrils. Overall, we show that amyloid fibril elongation is associated with a negative heat capacity, the magnitude of which correlates closely with the hydrophobic surface area that is buried upon fibril formation, highlighting the importance of hydrophobicity for fibril stability.

Impact of Removing Medicaid Fee-for-Service Hepatitis C Virus (HCV) Treatment Restrictions on HCV Provider Experience with Medicaid Managed Care Organizations in New York City.

Immediately after the approval of direct-acting antiviral medications for the treatment of hepatitis C virus (HCV) in 2013, state Medicaid programs limited access to these expensive treatments based on liver disease stage, absence of active alcohol or substance use, and prescriber limitations. New York State fee-for-service (FFS) Medicaid eliminated these requirements in May 2016, but the effect on providers and patients obtaining prior authorization (PA) from Medicaid managed care organizations (MCOs) was unknown. We used a mixed methods approach to assess whether the removal of HCV treatment restrictions was associated with changes in Medicaid MCOs' PA approval processes and length of time to treatment initiation at two large urban New York City provider organizations participating in Project INSPIRE, an HCV care coordination demonstration project. At baseline, the top criteria for clinic care coordinators ranking MCOs as being "most difficult" were liver staging criteria, delayed treatment, and requiring a urine toxicology test. At follow-up, liver staging criteria were replaced by medication formulary limitations. Univariate analysis of the Project INSPIRE participant data suggests a decrease in the percentage of participants with insurance/PA-related treatment delays pre- versus post-policy change (23% versus 15%, p value = 0.02). Interrupted time series analysis found a 2 percentage point decrease (p value = 0.02) in the proportion of PAs each month with insurance-related treatment delays that was attributable to policy change. These results from two urban clinics indicate New York State FFS Medicaid's policy change for HCV treatment may have been associated with some changes in Medicaid MCO PA decisions, but MCO PA denials and treatment delays were still observed "on the ground" by clinic staff.

Neural Correlates of Voice Perception in Newborns and the Influence of Preterm Birth.

Maternal voice is a highly relevant stimulus for newborns. Adult voice processing occurs in specific brain regions. Voice-specific brain areas in newborns and the relevance of an early vocal exposure on these networks have not been defined. This study investigates voice perception in newborns and the impact of prematurity on the cerebral processes. Functional magnetic resonance imaging (fMRI) and high-density electroencephalography (EEG) were used to explore the brain responses to maternal and stranger female voices in full-term newborns and preterm infants at term-equivalent age (TEA). fMRI results and the EEG oddball paradigm showed enhanced processing for voices in preterms at TEA than in full-term infants. Preterm infants showed additional cortical regions involved in voice processing in fMRI and a late mismatch response for maternal voice, considered as a first trace of a recognition process based on memory representation. Full-term newborns showed increased cerebral activity to the stranger voice. Results from fMRI, oddball, and standard auditory EEG paradigms highlighted important change detection responses to novelty after birth. These findings suggest that the main components of the adult voice-processing networks emerge early in development. Moreover, an early postnatal exposure to voices in premature infants might enhance their capacity to process voices.