Early childhood (1-5 years) obesity prevention: A systematic review of family-based multicomponent behavioral interventions.

INTRODUCTION: Globally 38.9 million children under age 5 have overweight or obesity, leading to type 2 diabetes, cardiovascular complications, depression, and poor educational outcomes. Obesity is difficult to reverse and lifestyle behaviors (healthy or unhealthy) can persist from 1.5 years of age. Targeting caregivers to help address modifiable behaviors may offer a viable solution. OBJECTIVE: Evaluate the impact of multicomponent family interventions on weight-based outcomes in early childhood and explore related secondary behavior outcomes. METHODS: Four databases were searched (1/2017-6/2022) for randomized controlled trials (RCTs) of obesity-prevention interventions for children (1-5 years). Eligible studies included an objectively measured weight-based outcome, family interventions targeting the caregiver or family, and interventions including at least two behavioral components of nutrition, physical activity, or sleep. RESULTS: Eleven interventions were identified consisting of four delivery modes: self-guided (n = 3), face-to-face group instruction (n = 3), face-to-face home visits (n = 2), and multiple levels of influence (n = 3). The reviewed studies reported almost no significant effects on child weight-based outcomes. Only two studies (one was an underpowered pilot study) resulted in significant positive child weight-management outcomes. Seven of the interventions significantly improved children's dietary intake. CONCLUSION: Except for one, the reviewed studies reported that family based interventions had no significant effects on child weight-based outcomes. Future studies of this type should include measurements of age and sex-based body mass index (BMI) and trajectories, and also examine other important benefits to the children and families.

Diabetes, brain health, and treatment gains in post-stroke aphasia.

In post-stroke aphasia, language improvements following speech therapy are variable and can only be partially explained by the lesion. Brain tissue integrity beyond the lesion (brain health) may influence language recovery and can be impacted by cardiovascular risk factors, notably diabetes. We examined the impact of diabetes on structural network integrity and language recovery. Seventy-eight participants with chronic post-stroke aphasia underwent six weeks of semantic and phonological language therapy. To quantify structural network integrity, we evaluated the ratio of long-to-short-range white matter fibers within each participant's whole brain connectome, as long-range fibers are more susceptible to vascular injury and have been linked to high level cognitive processing. We found that diabetes moderated the relationship between structural network integrity and naming improvement at 1 month post treatment. For participants without diabetes (n = 59), there was a positive relationship between structural network integrity and naming improvement (t = 2.19, p = 0.032). Among individuals with diabetes (n = 19), there were fewer treatment gains and virtually no association between structural network integrity and naming improvement. Our results indicate that structural network integrity is associated with treatment gains in aphasia for those without diabetes. These results highlight the importance of post-stroke structural white matter architectural integrity in aphasia recovery.

Inherited causes of exocrine pancreatic insufficiency in pediatric patients: clinical presentation and laboratory testing.

Pediatric patients with exocrine pancreatic insufficiency (EPI) have symptoms that include abdominal pain, weight loss or poor weight gain, malnutrition, and steatorrhea. This condition can be present at birth or develop during childhood for certain genetic disorders. Cystic fibrosis (CF) is the most prevalent disorder in which patients are screened for EPI; other disorders also are associated with pancreatic dysfunction, such as hereditary pancreatitis, Pearson syndrome, and Shwachman-Diamond syndrome. Understanding the clinical presentation and proposed pathophysiology of the pancreatic dysfunction of these disorders aids in diagnosis and treatment. Testing pancreatic function is challenging. Directly testing aspirates produced from the pancreas after stimulation is considered the gold standard, but the procedures are not standardized or widely available. Instead, indirect tests are often used in diagnosis and monitoring. Although indirect tests are more widely available and easier to perform, they have inherent limitations due to a lack of sensitivity and/or specificity for EPI.

Risk factors for endometrial cancer in Black women.

PURPOSE: The incidence of endometrial cancer (EC) has been increasing faster among Black women than among other racial/ethnic groups in the United States. Although the mortality rate is nearly twice as high among Black than White women, there is a paucity of literature on risk factors for EC among Black women, particularly regarding menopausal hormone use and severe obesity. METHODS: We pooled questionnaire data on 811 EC cases and 3,124 controls from eight studies with data on self-identified Black women (4 case-control and 4 cohort studies). We analyzed cohort studies as nested case-control studies with up to 4 controls selected per case. We used logistic regression to estimate multivariable-adjusted odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: We observed a positive association between BMI and EC incidence (Ptrend < 0.0001) The OR comparing BMI ≥ 40 vs. < 25 kg/m2 was 3.92 (95% CI 2.91, 5.27). Abdominal obesity among those with BMI < 30 kg/m2 was not appreciably associated with EC risk (OR 1.21, 95% CI 0.74, 1.99). Associations of reproductive history with EC were similar to those observed in studies of White women. Long-term use of estrogen-only menopausal hormones was associated with an increased risk of EC (≥ 5 years vs. never use: OR 2.08, 95% CI: 1.06, 4.06). CONCLUSIONS: Our results suggest that the associations of established risk factors with EC are similar between Black and White women. Other explanations, such as differences in the prevalence of known risk factors or previously unidentified risk factors likely underlie the recent increases in EC incidence among Black women.

The Costs of Implementing a Conversation Aid for Uterine Fibroids in Multiple Health Care Settings.

BACKGROUND: Health care organizations considering adopting a conversation aid (CA), a type of patient decision aid innovation, need information about the costs of implementation. OBJECTIVES: The aims of this study were to: (1) calculate the costs of introducing a CA in a study of supported implementation in 5 gynecologic settings that manage individuals diagnosed with uterine fibroids and (2) estimate the potential costs of future clinical implementation efforts in hypothetical settings. RESEARCH DESIGN: We used time-driven activity-based costing to estimate the costs of CA implementation at multiple steps: integration with an electronic health record, preimplementation, implementation, and sustainability. We then estimated costs for 2 disparate hypothetical implementation scenarios. SUBJECTS AND DATA COLLECTION: We conducted semistructured interviews with participants and examined internal documentation. RESULTS: We interviewed 41 individuals, analyzed 51 documents and 100 emails. Overall total implementation costs over ∼36 months of activities varied significantly across the 5 settings, ranging from $14,157 to $69,134. Factors influencing costs included size/complexity of the setting, urban/rural location, practice culture, and capacity to automate patient identification. Initial investments were substantial, comprising mostly personnel time. Settings that embedded CA use into standard workflows and automated identification of appropriate patients had the lowest initial investment and sustainability costs. Our estimates of the costs of sustaining implementation were much lower than initial investments and mostly attributable to CA subscription fees. CONCLUSION: Initiation and implementation of the interventions require significant personnel effort. Ongoing costs to maintain use are much lower and are a small fraction of overall organizational operating costs.

Dental evaluation and clearance prior to allogeneic hematopoietic cell transplantation.

INTRODUCTION: Dental examination and stabilization are performed prior to allogeneic hematopoietic cell transplantation to decrease infection risk during neutropenia. Burden of dental disease and treatment need is not well characterized in this population. OBJECTIVES: This report describes the dental status of a cohort of patients within the Chronic Graft-versus-Host Disease Consortium and treatment rendered prior to transplant. METHODS: The cohort included 486 subjects (Fred Hutchinson: n = 245; Dana-Farber: n = 241). Both centers have institutional-based dental clearance programs. Data were retrospectively abstracted from medical records by calibrated oral health specialists. RESULTS: The median age at transplant was 55.9 years, 62.1% were male, and 88% were white. Thirteen patients were edentulous (2.7%). The mean teeth among dentate patients before clearance was 26.0 (SD, 4.6). Dental findings included untreated caries (31.2%), restorations (91.6%), endodontically treated teeth (48.1%), and dental implants (5.7%). Pretransplant procedures during clearance included endodontic therapy (3.6%; mean = 0.1 teeth), restorations (25.1%; mean = 0.7), dental prophylaxis (59.2%), scaling/root planing (5.1%), and extraction (13.2%; mean = 0.3). The mean teeth after clearance was 25.6 (SD, 5.0). CONCLUSIONS: Retrospective analysis of pre-AlloHCT dental data in subjects at two large transplant centers identified low levels of dental need. Findings suggest high access to care.

The CONFIDENT study protocol: a randomized controlled trial comparing two methods to increase long-term care worker confidence in the COVID-19 vaccines.

BACKGROUND: Clinical and real-world effectiveness data for the COVID-19 vaccines have shown that they are the best defense in preventing severe illness and death throughout the pandemic. However, in the US, some groups remain more hesitant than others about receiving COVID-19 vaccines. One important group is long-term care workers (LTCWs), especially because they risk infecting the vulnerable and clinically complex populations they serve. There is a lack of research about how best to increase vaccine confidence, especially in frontline LTCWs and healthcare staff. Our aims are to: (1) compare the impact of two interventions delivered online to enhanced usual practice on LTCW COVID-19 vaccine confidence and other pre-specified secondary outcomes, (2) determine if LTCWs' characteristics and other factors mediate and moderate the interventions' effect on study outcomes, and (3) explore the implementation characteristics, contexts, and processes needed to sustain a wider use of the interventions. METHODS: We will conduct a three-arm randomized controlled effectiveness-implementation hybrid (type 2) trial, with randomization at the participant level. Arm 1 is a dialogue-based webinar intervention facilitated by a LTCW and a medical expert and guided by an evidence-based COVID-19 vaccine decision tool. Arm 2 is a curated social media web application intervention featuring interactive, dynamic content about COVID-19 and relevant vaccines. Arm 3 is enhanced usual practice, which directs participants to online public health information about COVID-19 vaccines. Participants will be recruited via online posts and advertisements, email invitations, and in-person visits to care settings. Trial data will be collected at four time points using online surveys. The primary outcome is COVID-19 vaccine confidence. Secondary outcomes include vaccine uptake, vaccine and booster intent for those unvaccinated, likelihood of recommending vaccination (both initial series and booster), feeling informed about the vaccines, identification of vaccine information and misinformation, and trust in COVID-19 vaccine information provided by different people and organizations. Exploration of intervention implementation will involve interviews with study participants and other stakeholders, an in-depth process evaluation, and testing during a subsequent sustainability phase. DISCUSSION: Study findings will contribute new knowledge about how to increase COVID-19 vaccine confidence and effective informational modalities for LTCWs. TRIAL REGISTRATION: NCT05168800 at ClinicalTrials.gov, registered December 23, 2021.

Descriptive analyses of bacterial communities in marine sediment microcosms spiked with fish wastes, emamectin benzoate, and oxytetracycline.

In marine sediments surrounding salmon aquaculture sites, organic matter (OM) enrichment has been shown to influence resident bacterial community composition; however, additional effects on these communities due to combined use of the sea-lice therapeutant emamectin benzoate (EMB) and the widely used antibiotic oxytetracycline (OTC) are unknown. Here, we use sediment microcosms to assess the influence of OM, EMB, and OTC on benthic bacterial communities. Microcosms consisted of mud or sand sediments enriched with OM (fish and feed wastes) and spiked with EMB and OTC at environmentally-relevant concentrations. Samples were collected from initial matrices at the initiation of the trial and after 110 days for 16 S rRNA gene sequencing of the V3-V4 region and microbiome profiling. The addition of OM in both mud and sand sediments reduced alpha diversities; for example, an average of 1106 amplicon sequence variants (ASVs) were detected in mud with no OM addition, while only 729 and 596 ASVs were detected in mud with low OM and high OM, respectively. Sediments enriched with OM had higher relative abundances of Spirochaetota, Firmicutes, and Bacteroidota. For instance, Spirochaetota were detected in sediments with no OM with a relative abundance range of 0.01-1.2%, while in sediments enriched with OM relative abundance varied from 0.16% to 26.1%. In contrast, the addition of EMB (60 ng/g) or OTC (150 ng/g) did not result in distinct taxonomic shifts in the bacterial communities compared to un-spiked sediments during the timeline of this experiment. EMB and OTC concentrations may have been below effective inhibitor concentrations for taxa in these communities; further work should explore gene content and the presence of antibiotic resistance genes (ARGs) in sediment-dwelling bacteria.

The pivotal role of cytotoxic NK cells in mediating the therapeutic effect of anti-CD47 therapy in mycosis fungoides.

CD47 is frequently overexpressed on tumor cells and is an attractive therapeutic target. The mechanism by which anti-CD47 immunotherapy eliminates cutaneous lymphoma has not been explored. We utilized CRISPR/Cas-9 CD47 knock-out, depletion of NK cells, and mice genetically deficient in IFN-γ to elucidate the mechanism of anti-CD47 therapy in a murine model of cutaneous T cell lymphoma (CTCL). CD47 was found to be a crucial factor for tumor progression since CD47 KO CTCL exhibited a delay in tumor growth. The treatment of CD47 WT murine CTCL with anti-CD47 antibodies led to a significant reduction in tumor burden as early as four days after the first treatment and accompanied by an increased percentage of cytotoxic NK cells at the tumor site. The depletion of NK cells resulted in marked attenuation of the anti-tumor effect of anti-CD47. Notably, the treatment of CD47 WT tumors in IFN-γ KO mice with anti-CD47 antibodies was efficient, demonstrating that IFN-γ was not required to mediate anti-CD47 therapy. We were able to potentiate the therapeutic effect of anti-CD47 therapy by IFN-α. That combination resulted in an increased number of cytotoxic CD107a + IFN-γ-NK1.1 cells and intermediate CD62L + NKG2a-NK1.1. Correlative data from a clinical trial (clinicaltrials.gov, NCT02890368) in patients with CTCL utilizing SIRPαFc to block CD47 confirmed our in vivo observations.

Refining reproductive risk for FMR1 premutation carriers in the general obstetric population.

Female FMR1 premutation (FMR1 PM) carriers for fragile X syndrome (FXS) are at risk to have a child with FXS based on their CGG repeat size and AGG interruption number. Studies examining this risk in unselected populations of female PM carriers are lacking. This retrospective cohort study analyzed carrier status, CGG repeat length, AGG interruption result, and reproductive risk refinement in a population of female patients who underwent routine carrier screening for FXS. A total of 1536 PM carriers (0.43%) were identified, 95% of whom had between 55 and 90 CGG repeats. A number of 1334 carriers underwent AGG interruption testing. The majority had at least one AGG interruption and received a lower reproductive risk for FXS following AGG interruption testing (89% and 85%, respectively) as compared to their risk calculated based on CGG repeat size alone. The average change in risk across the population following AGG interruption testing was -3.4%, with a range from -50.8% to 48.9%. This article describes the range of CGG repeats and AGG interruptions in an unselected population of female PM carriers and suggests that most carriers would benefit from AGG interruption testing to refine their reproductive risk of having a child with FXS.

Fluoroscopic Evaluation of Duodenal Diseases.

The duodenum can be affected by a variety of abnormalities because of its development during embryogenesis and its dual intra- and retroperitoneal location. If small bowel embryogenesis is disturbed, congenital errors occur. Although some congenital variants may be asymptomatic and inconsequential to the patient, other anomalies can result in life-threatening emergencies such as malrotation, leading to midgut volvulus. Many infectious processes affect the duodenum, including duodenal ulcers and opportunistic infection in patients with HIV/AIDS or Crohn disease. Small bowel malignancies are uncommon but important to recognize, because the duodenum can be involved in polyposis syndromes or the development of primary adenocarcinoma, neuroendocrine tumors, lymphoma, and metastasis. Although endoscopy is currently the most used diagnostic method to assess the lumen of the upper gastrointestinal tract, fluoroscopy is a valuable adjunct technique and the study of choice for many diseases, specifically those for which anatomic and functional information is required. Fluoroscopy is also commonly used postoperatively to assess for complications such as obstruction and extraluminal leaks. Compared with endoscopy, fluoroscopy is an inexpensive and noninvasive technique that provides salient anatomic information and allows delineation of the duodenal mucosa and assessment of real-time duodenal motility. The authors examine the broad spectrum of conditions that can involve the duodenum, including congenital, infectious, inflammatory, and neoplastic abnormalities, and review their typical appearances at fluoroscopy. Online supplemental material is available for this article. ©RSNA, 2022.

Dollars for Diagnosis: A Single-Institutional Analysis of Billing for Intraoperative Transesophageal Echocardiography Examinations.

OBJECTIVES: The authors sought to identify correctable reasons for the failed completion of required billing elements necessary for the reimbursement of services for intraoperative transesophageal echocardiography (TEE). DESIGN: This was a retrospective study. SETTING: This study was completed at a single institution and large academic center. PARTICIPANTS: The patient population included all adult patients who underwent cardiac surgery at a single academic center over one year. INTERVENTIONS: This retrospective review of TEE documentation and billing data was performed for the all adults undergoing cardiac surgery over the course of one year. METHODS AND MAIN RESULTS: Documentation characteristics were compared between examinations that were reimbursed and those that were not. Out of 504 TEE examinations, 30% were not reimbursed. For these examinations, there was a lower compliance in the completion of minimum billing requirements, compared with those that were reimbursed; designation as "diagnostic" (29% v 93%, respectively, p < 0.0001), procedure note (70% v 99%, p < 0.0001), and procedure order (67% v 98%, p = 0.0002). The total estimated annual loss in revenue was $36,000. CONCLUSIONS: Understanding documentation requirements for TEE is an overlooked but important part of anesthesiology practice that may lead to substantial cost savings. Completion of a procedure note, procedure order, and documentation of an examination as "diagnostic" was associated with successful billing.

Co-Development of a Web Application (COVID-19 Social Site) for Long-Term Care Workers ("Something for Us"): User-Centered Design and Participatory Research Study.

BACKGROUND: Improving confidence in and uptake of COVID-19 vaccines and boosters among long-term care workers (LTCWs) is a crucial public health goal, given their role in the care of elderly people and people at risk. While difficult to reach with workplace communication interventions, most LTCWs regularly use social media and smartphones. Various social media interventions have improved attitudes and uptake for other vaccines and hold promise for the LTCW population. OBJECTIVE: We aimed to develop a curated social web application (interactive website) to increase COVID-19 vaccine confidence (a 3-arm randomized trial is underway). METHODS: Following user-centric design and participatory research approaches, we undertook the following 3 steps: (1) content identification, (2) platform development, and (3) community building. A LTCW and stakeholder advisory group provided iterative input. For content identification (step 1), we identified topics of concern about COVID-19 vaccines via desktop research (published literature, public opinion polls, and social media monitoring), refined by interviewing and polling LTCWs. We also conducted a national online panel survey. We curated and fact-checked posts from popular social media platforms that addressed the identified concerns. During platform development (step 2), we solicited preferences for design and functionality via interviews and user experience testing with LTCWs. We also identified best practices for online community building (step 3). RESULTS: In the interviews (n=9), we identified 3 themes: (1) LTCWs are proud of their work but feel undervalued; (2) LTCWs have varying levels of trust in COVID-19-related information; and (3) LTCWs would welcome a curated COVID-19 resource that is easy to understand and use-"something for us". Through desktop research, LTCW interviews, and our national online panel survey (n=592) we found that participants are interested in information about COVID-19 in general, vaccine benefits, vaccine risks, and vaccine development. Content identification resulted in 434 posts addressing these topic areas, with 209 uploaded to the final web application. Our LTCW poll (n=8) revealed preferences for personal stories and video content. The platform we developed is an accessible WordPress-based social media web application, refined through formal (n=3) and informal user experience testing. Users can sort posts by topic or subtopic and react to or comment on posts. To build an online community, we recruited 3 LTCW "community ambassadors" and instructed them to encourage discussion, acknowledge concerns, and offer factual information on COVID-19 vaccines. We also set "community standards" for the web application. CONCLUSIONS: An iterative, user-centric, participatory approach led to the launch of an accessible social media web application with curated content for COVID-19 vaccines targeting LTCWs in the United States. Through our trial, we will determine if this approach successfully improves vaccine confidence. If so, a similar social media resource could be used to develop curated social media interventions in other populations and with other public health goals.

The impact of social disadvantage on autonomic physiology of latinx adolescents: The role of environmental risks.

The experience of poverty embodies complex, multidimensional stressors that may adversely affect physiological and psychological domains of functioning. Compounded by racial/ethnic discrimination, the financial aspect of family poverty typically coincides with additional social and physical environmental risks such as pollution exposure, housing burden, elevated neighborhood unemployment, and lower neighborhood education levels. In this study, we investigated the associations of multidimensional social disadvantage throughout adolescence with autonomic nervous system (ANS) functioning at 17 years. Two hundred and twenty nine low-income Mexican-American adolescents (48.6% female) and their parents were assessed annually between the ages of 10 and 16. Participants' census tracts were matched with corresponding annual administrative data of neighborhood housing burden, education, unemployment, drinking water quality, and fine particulate matter. We combined measures of adolescents' electrodermal response and respiratory sinuses arrhythmia at rest and during a social exclusion challenge (Cyberball) to use as ANS indices of sympathetic and parasympathetic activity, respectively. Controlling for family income-to-needs, youth exposed to greater cumulative water and air pollution from ages 10-16 displayed altered patterns of autonomic functioning at rest and during the social challenge. Conversely, youth living in areas with higher housing burden displayed healthy patterns of autonomic functioning. Altogether, results suggest that toxin exposure in youths' physical environments disrupts the ANS, representing a plausible mechanism by which pollutants and social disadvantage influence later physical and mental health.

Prophylactic corticosteroid use in patients receiving axicabtagene ciloleucel for large B-cell lymphoma.

ZUMA-1 (NCT02348216) examined the safety and efficacy of axicabtagene ciloleucel (axi-cel), an autologous CD19-directed chimaeric antigen receptor (CAR)-T cell therapy, in refractory large B-cell lymphoma. To reduce treatment-related toxicity, several exploratory safety management cohorts were added to ZUMA-1. Specifically, cohort 6 investigated management of cytokine release syndrome (CRS) and neurologic events (NEs) with prophylactic corticosteroids and earlier corticosteroid and tocilizumab intervention. CRS and NE incidence and severity were primary end-points. Following leukapheresis, patients could receive optional bridging therapy per investigator discretion. All patients received conditioning chemotherapy (days -5 through -3), 2 × 106  CAR-T cells/kg (day 0) and once-daily oral dexamethasone [10 mg, day 0 (before axi-cel) through day 2]. Forty patients received axi-cel. CRS occurred in 80% of patients (all grade ≤2). Any grade and grade 3 or higher NEs occurred in 58% and 13% of patients respectively. Sixty-eight per cent of patients did not experience CRS or NEs within 72 h of axi-cel. With a median follow-up of 8·9 months, objective and complete response rates were 95% and 80% respectively. Overall, prophylactic corticosteroids and earlier corticosteroid and/or tocilizumab intervention resulted in no grade 3 or higher CRS, a low rate of grade 3 or higher NEs and high response rates in this study population.

Professionally responsible coronavirus disease 2019 vaccination counseling of obstetrical and gynecologic patients.

The development of coronavirus disease 2019 vaccines in the current and planned clinical trials is essential for the success of a public health response. This paper focuses on how physicians should implement the results of these clinical trials when counseling patients who are pregnant, planning to become pregnant, breastfeeding or planning to breastfeed about vaccines with government authorization for clinical use. Determining the most effective approach to counsel patients about coronavirus disease 2019 vaccination is challenging. We address the professionally responsible counseling of 3 groups of patients-those who are pregnant, those planning to become pregnant, and those breastfeeding or planning to breastfeed. We begin with an evidence-based account of the following 5 major challenges: the limited evidence base, the documented increased risk for severe disease among pregnant coronavirus disease 2019-infected patients, conflicting guidance from government agencies and professional associations, false information about coronavirus disease 2019 vaccines, and maternal mistrust and vaccine hesitancy. We subsequently provide evidence-based, ethically justified, practical guidance for meeting these challenges in the professionally responsible counseling of patients about coronavirus disease 2019 vaccination. To guide the professionally responsible counseling of patients who are pregnant, planning to become pregnant, and breastfeeding or planning to breastfeed, we explain how obstetrician-gynecologists should evaluate the current clinical information, why a recommendation of coronavirus disease 2019 vaccination should be made, and how this assessment should be presented to patients during the informed consent process with the goal of empowering them to make informed decisions. We also present a proactive account of how to respond when patients refuse the recommended vaccination, including the elements of the legal obligation of informed refusal and the ethical obligation to ask patients to reconsider. During this process, the physician should be alert to vaccine hesitancy, ask patients to express their hesitation and reasons for it, and respectfully address them. In contrast to the conflicting guidance from government agencies and professional associations, evidence-based professional ethics in obstetrics and gynecology provides unequivocal and clear guidance: Physicians should recommend coronavirus disease 2019 vaccination to patients who are pregnant, planning to become pregnant, and breastfeeding or planning to breastfeed. To prevent widening of the health inequities, build trust in the health benefits of vaccination, and encourage coronavirus disease 2019 vaccine and treatment uptake, in addition to recommending coronavirus disease 2019 vaccinations, physicians should engage with communities to tailor strategies to overcome mistrust and deliver evidence-based information, robust educational campaigns, and novel approaches to immunization.

Tximeta: Reference sequence checksums for provenance identification in RNA-seq.

Correct annotation metadata is critical for reproducible and accurate RNA-seq analysis. When files are shared publicly or among collaborators with incorrect or missing annotation metadata, it becomes difficult or impossible to reproduce bioinformatic analyses from raw data. It also makes it more difficult to locate the transcriptomic features, such as transcripts or genes, in their proper genomic context, which is necessary for overlapping expression data with other datasets. We provide a solution in the form of an R/Bioconductor package tximeta that performs numerous annotation and metadata gathering tasks automatically on behalf of users during the import of transcript quantification files. The correct reference transcriptome is identified via a hashed checksum stored in the quantification output, and key transcript databases are downloaded and cached locally. The computational paradigm of automatically adding annotation metadata based on reference sequence checksums can greatly facilitate genomic workflows, by helping to reduce overhead during bioinformatic analyses, preventing costly bioinformatic mistakes, and promoting computational reproducibility. The tximeta package is available at https://bioconductor.org/packages/tximeta.

Structure of the toxic core of α-synuclein from invisible crystals.

The protein α-synuclein is the main component of Lewy bodies, the neuron-associated aggregates seen in Parkinson disease and other neurodegenerative pathologies. An 11-residue segment, which we term NACore, appears to be responsible for amyloid formation and cytotoxicity of human α-synuclein. Here we describe crystals of NACore that have dimensions smaller than the wavelength of visible light and thus are invisible by optical microscopy. As the crystals are thousands of times too small for structure determination by synchrotron X-ray diffraction, we use micro-electron diffraction to determine the structure at atomic resolution. The 1.4 Å resolution structure demonstrates that this method can determine previously unknown protein structures and here yields, to our knowledge, the highest resolution achieved by any cryo-electron microscopy method to date. The structure exhibits protofibrils built of pairs of face-to-face ß-sheets. X-ray fibre diffraction patterns show the similarity of NACore to toxic fibrils of full-length α-synuclein. The NACore structure, together with that of a second segment, inspires a model for most of the ordered portion of the toxic, full-length α-synuclein fibril, presenting opportunities for the design of inhibitors of α-synuclein fibrils.

Determinants, circumstances and consequences of injurious falls among older women living in the community.

OBJECTIVE: To identify the risk factors of women who fell with injury relative to women who did not fall or fell without injury and to describe the circumstances and consequences of injurious and non-injurious falls. METHODS: We analysed 5074 older women from the Objective Physical Activity and Cardiovascular Health Study who prospectively tracked their falls using a 13-month calendar. Women with a reported fall were phone interviewed about fall-related details, including injuries. Risk factors were identified from surveys and clinical home visits. Logistic regression models were used to calculate adjusted ORs and 95% CIs for injurious falls relative to not falling or falling without injury. Circumstances of injurious and non-injurious falls were compared. RESULTS: At least one fall was experienced by 1481 (29%) participants. Of these, 1043 were phone interviewed, of whom 430 (41%) reported at least one injurious fall. Relative to not falling, the risk factor most strongly associated with experiencing an injurious fall was having fallen ≥2 times (OR 4.0, CI 2.7 to 5.8) in the past year. Being black was protective for fall-related injury (OR 0.6, CI 0.4 to 0.9). No strong associations in risk factors were observed for injurious relative to non-injurious falls. Injurious falls were more likely to occur away from and outside of the home (p<0.05). Over half of those who injured self-managed their injury. CONCLUSION: Falling repeatedly is a powerful risk factor for injurious falls. Those who have fallen more than once should be prioritised for interventions to mitigate the risk of an injurious fall.

Correction: Defining the genetic susceptibility to cervical neoplasia-A genome-wide association study.

[This corrects the article DOI: 10.1371/journal.pgen.1006866.].