SGN-CD228A Is an Investigational CD228-Directed Antibody-Drug Conjugate with Potent Antitumor Activity across a Wide Spectrum of Preclinical Solid Tumor Models.

SGN-CD228A is an investigational antibody-drug conjugate (ADC) directed to melanotransferrin (CD228, MELTF, MFI2, p97), a cell-surface protein first identified in melanoma. SGN-CD228A consists of a humanized antibody, hL49, with high specificity and affinity for CD228 that is stably conjugated to 8 molecules of the clinically validated microtubule-disrupting agent monomethyl auristatin E (MMAE) via a novel glucuronide linker. We performed comprehensive IHC studies, which corroborated published RNA sequencing data and confirmed low CD228 expression in normal tissues and high expression in several cancers, including melanoma, squamous non-small cell lung cancer (NSCLC), triple-negative breast cancer (TNBC), colorectal cancer, and pancreatic cancer. SGN-CD228A was efficiently internalized in various tumor cell types, and its cytotoxic activity was dependent on CD228 expression and internalization and intrinsic sensitivity to the MMAE payload. Compared with the valine-citrulline dipeptide linker, the novel glucuronide linker increased the cellular retention of MMAE in vitro and conferred improved antitumor activity against melanoma cell lines in vitro and in vivo. In addition, SGN-CD228A was active across melanoma, TNBC, and NSCLC cell line- and patient-derived xenograft models with heterogeneous antigen expression. In vivo, CD228 expression was important for response to SGN-CD228A but was not well correlated across all tumor types, suggesting that other factors associated with ADC activity are important. Overall, SGN-CD228A is a CD228-directed, investigational ADC that employs innovative technology and has compelling preclinical antitumor activity. SGN-CD228A is investigated in a Phase I clinical trial (NCT04042480) in patients with advanced solid tumors.

Regional citrate anticoagulation versus systemic heparin anticoagulation for continuous kidney replacement therapy in intensive care.

PURPOSE: Many intensive care units (ICUs) have transitioned from systemic heparin anticoagulation (SHA) to regional citrate anticoagulation (RCA) for continuous kidney replacement therapy (CKRT). We evaluated the clinical and health economic impacts of ICU transition to RCA. MATERIALS AND METHODS: We surveyed all adult general ICUs in England and Wales to identify transition dates and conducted a micro-costing study in eight ICUs. We then conducted an interrupted time-series analysis of linked, routinely collected health records. RESULTS: In 69,001 patients who received CKRT (8585 RCA, 60,416 SHA) in 181 ICUs between 2009 and 2017, transition to RCA was not associated with a change in 90-day mortality (adjusted odds ratio 0.98, 95% CI 0.89-1.08) but was associated with step-increases in duration of kidney support (0.53 days, 95% CI 0.28-0.79), advanced cardiovascular support (0.23 days, 95% CI 0.09-0.38) and ICU length of stay (0.86 days, 95% CI 0.24-1.49). The estimated one-year incremental net monetary benefit per patient was £ - 2376 (95% CI £ - 3841-£ - 911), with an estimated likelihood of cost-effectiveness of <0.1%. CONCLUSIONS: Transition to RCA was associated with significant increases in healthcare resource use, without corresponding clinical benefit, and is highly unlikely to be cost-effective over a one-year time horizon.

The prevalence of obstructive sleep apnoea risk factors in individuals with cognitive impairment: south London cross-sectional study.

AIMS AND METHOD: We aimed to determine the prevalence of risk factors for obstructive sleep apnoea (OSA) in patients with mild cognitive impairment (MCI) or dementia. Using patient records across a 5 year period, we identified 16 855 patients with dementia or MCI. We gave scores for keywords relating to each modified STOP BANG parameter in patient progress notes. Based on individual scores, we stratified the population into groups with low, intermediate and high risk of OSA. RESULTS: Our population had a high prevalence of risk factors and consequently high risk scores for OSA (18.21% high risk). Parameters directly related to sleep had a low prevalence. CLINICAL IMPLICATIONS: The risk of developing or having OSA is high among patients with MCI and dementia. Low sleep parameter frequency probably suggests poor documentation of sleep rather than true prevalence. Our findings support the implementation of the STOP BANG or a similar screening tool as a standardised method to identify OSA risk in memory clinics.

Effects of Multiple Local Environments on Electron Energy Loss Spectra of Epitaxial Perovskite Interfaces.

The role of local chemical environments in the electron energy loss spectra of complex multiferroic oxides was studied using computational and experimental techniques. The evolution of the O K-edge across an interface between bismuth ferrite (BFO) and lanthanum strontium manganate (LSMO) was considered through spectral averaging over crystallographically equivalent positions to capture the periodicity of the local O environments. Computational techniques were used to investigate the contribution of individual atomic environments to the overall spectrum, and the role of doping and strain was considered. Chemical variation, even at the low level, was found to have a major impact on the spectral features, whereas strain only induced a small chemical shift to the edge onset energy. Through a combination of these methods, it was possible to explain experimentally observed effects such as spectral flattening near the interface as the combination of spectral responses from multiple local atomic environments.

Social media use and body image issues among adolescents in a vulnerable Louisiana community.

Widespread concern has been expressed regarding unrealistic body image and adolescent eating disorder promoting content on social media (SM) platforms. Numerous research studies have examined the impact of SM on body image as well as social vulnerability on negative mental health outcomes. Despite this, few previous studies have examined the impact of SM on body image specifically in vulnerable, underserved, or predominantly minority communities. This study examines the impact of SM on body image issues (BII) in adolescents in a public school system where greater than 50% of the students live in impoverished households. In late 2019, high school student leaders in Northwest Louisiana developed a survey alongside Step Forward, a collective impact initiative. Questions investigated adolescent SM use and mental health in Caddo Parish, namely BII. Teachers within Caddo Parish Public School System administered the survey. Out of the 11,248 total high school students in the school system, nearly 50% were sampled for a sample size of 5,070. Hypotheses included: (1) females were more likely to use SM than males, (2) increasing time spent on SM would correlate with females reporting BII, with males remaining largely unaffected, and (3) highly visual social media (HVSM) platforms would be associated with greater reports of BII than non-HVSM platforms. Results showed females were more likely to use SM (p < 0.001) and report BII (p < 0.001) compared to males, while both sexes reported BII with increasing time spent on SM (p < 0.001). A diversity of platforms were associated with increased BII among SM users compared to non-users (p < 0.001): Pinterest, Reddit, Snapchat, TikTok, Twitter, and YouTube. This conclusion is tempered by the omission of race as a variable in the study design, the use of self-report, and the use of an unvalidated instrument. These findings suggest that the harmful association between SM use and BII may transcend culture and socioeconomic status for a broadly deleterious effect on adolescent mental wellbeing.

Renal replacement anticoagulant management: Protocol and analysis plan for an observational comparative effectiveness study of linked data sources.

Acute kidney injury is common in critical illness. In patients with severe acute kidney injury, renal replacement therapy is needed to prevent harm from metabolic and electrolyte disturbances and fluid overload. In the UK, continuous renal replacement therapy (CRRT) is the preferred modality, which requires anticoagulation. Over the last decade, conventional systemic heparin anticoagulation has started being replaced by regional citrate anticoagulation for CRRT, which is now used in approximately 50% of ICUs. This shift towards regional citrate anticoagulation for CRRT is occurring with little evidence of safety or longer term effectiveness. Renal replacement anticoagulant management (RRAM) is an observational comparative effectiveness study, utilising existing data sources to address the clinical and cost-effectiveness of the change to regional citrate anticoagulation for CRRT in UK ICUs. The study will use data from approximately 85,000 patients who were treated in adult, general ICUs participating in the case mix programme national clinical audit between 1 April 2009 and 31 March 2017. A survey of health service providers' anticoagulation practices will be combined with treatment and hospital outcome data from the case mix programme and linked with long-term outcomes from the Civil Registrations (deaths), Hospital Episodes Statistics for England, Patient Episodes Data for Wales, and the UK Renal Registry datasets. The primary clinical effectiveness outcome is all-cause mortality at 90-days. The study will incorporate an economic evaluation with micro-costing of both regional citrate anticoagulation and systemic heparin anticoagulation. Study registration: NCT03545750.

Teen Advisory Council Survey's Factors Associated With Self-Harming Thoughts.

Background: The evaluation of teens with self-harming thoughts (SHT) is a high-stakes task for physicians in community and emergency department (ED) settings. The lived experience of adolescents with stress and SHT provides an important source of insight for mental health professionals who evaluate and treat teens A snapshot of the lived experience of teens in northwest Louisiana was captured by the Step Forward Teen Advisory Council (TAC) in 2019. The TAC surveyed peers with the goal of identifying common stressors experienced by local teens in order to inform policy and practices in the local school system. The identification of stressors is a critical step in addressing SHT as adolescents who experience life stressors are at increased risk for self-harming thoughts (SHT), a known precursor to self-harm and suicide. Assessing youth for life stressors is a critical element of suicide prevention. Methods: Local teens queried 5,070 peers attending Caddo Parish schools to better understand the stressors faced by high school students in Northwest Louisiana using a student developed survey. Results were presented to peers at a virtual summit where teens developed action items to reduce stress and presented findings to local leaders. Their efforts ultimately lead to increased supports for students in local schools. Results: Over half of the teens surveyed reported stressors that negatively impacted their physical or emotional well-being. Students endorsing self-harming thoughts reported an average of 7.82 stressors as compared to 3.47 in peers without SHT. Teens with stressors at both home and school were more likely to experience SHT than teens with stressors in a single location. Conclusion: The Gen Z students who developed the TAC Survey identified stress as a major concern for teens in Northwest Louisiana. The TAC Survey data aligns local experience with established data regarding the association between stress, depression and SHT. Second, the results highlight the importance of diving deep to identify all stressors when assessing the risk of self-harm. Finally, the lived experience of local teens with SHT provides critical information for professionals to better understand risk for SHT and suicide in our region and beyond.

Inclusion of the US Preventive Services Task Force Recommendation for Mammography in State Comprehensive Cancer Control Plans in the US.

Importance: The recommendations for the age and frequency that women at average risk for breast cancer should undergo breast cancer mammography screening have been a matter of emotional, political, and scientific debate over the past decades. Multiple national organizations provide recommendations for breast cancer screening age and frequency. US Centers for Disease Control and Prevention (CDC) funding for state comprehensive cancer control (CCC) planning requires compliance with stated objectives for attaining goals. US Preventive Services Task Force (USPSTF) recommendations on cancer prevention and control are currently used to require coverage of prevention services. Objectives: To evaluate the consistency of state CCC plan objectives compared with the most current (2016) USPSTF recommendations for the age and frequency that individuals should undergo mammography screening and to make recommendations for improvement of state CCC plans. Design, Setting, and Participants: This cross-sectional study used a descriptive, point-in-time evaluation and was conducted from November 1, 2019, to June 30, 2021. In November 2019, the most recent CCC plans from 50 US states and the District of Columbia were downloaded from the CDC website. The recommended ages at which to begin and end mammography examinations and the frequency of mammography examinations were extracted from plan objectives. Main Outcomes and Measures: The recommendations found in CCC plan objectives regarding the ages at which to begin and end mammography examinations and the frequency of mammography examinations for women with average risk for breast cancer were compared with USPSTF recommendations. Results: Of the 51 CCC plans, 16 (31%) were consistent with all USPSTF recommendations for age and frequency that women at average risk should undergo mammography. Twenty-six plans (51%) were partially consistent with recommendations, and 9 plans (18%) were not consistent with any of the 3 guideline components. Conclusions and Relevance: Compared with the USPSTF recommendation, state CCC plans are not homogenous regarding the age and frequency that women at average risk for breast cancer should undergo mammography. This variation is partially due to differences in state-specific planning considerations and discretion, variations in recommendations among national organizations, and publication of plans prior to the most current USPSTF recommendation (2016). Specifying the concept that high-risk populations need different age and frequency of screening recommendations than the general population may reduce heterogeneity among plans.

Heparin versus citrate anticoagulation for continuous renal replacement therapy in intensive care: the RRAM observational study.

BACKGROUND: In the UK, 10% of admissions to intensive care units receive continuous renal replacement therapy with regional citrate anticoagulation replacing systemic heparin anticoagulation over the last decade. Regional citrate anticoagulation is now used in > 50% of intensive care units, despite little evidence of safety or effectiveness. AIM: The aim of the Renal Replacement Anticoagulant Management study was to evaluate the clinical and health economic impacts of intensive care units moving from systemic heparin anticoagulation to regional citrate anticoagulation for continuous renal replacement therapy. DESIGN: This was an observational comparative effectiveness study. SETTING: The setting was NHS adult general intensive care units in England and Wales. PARTICIPANTS: Participants were adults receiving continuous renal replacement therapy in an intensive care unit participating in the Intensive Care National Audit & Research Centre Case Mix Programme national clinical audit between 1 April 2009 and 31 March 2017. INTERVENTIONS: Exposure - continuous renal replacement therapy in an intensive care unit after completion of transition to regional citrate anticoagulation. Comparator - continuous renal replacement therapy in an intensive care unit before starting transition to regional citrate anticoagulation or had not transitioned. OUTCOME MEASURES: Primary effectiveness - all-cause mortality at 90 days. Primary economic - incremental net monetary benefit at 1 year. Secondary outcomes - mortality at hospital discharge, 30 days and 1 year; days of renal, cardiovascular and advanced respiratory support in intensive care unit; length of stay in intensive care unit and hospital; bleeding and thromboembolic events; prevalence of end-stage renal disease at 1 year; and estimated lifetime incremental net monetary benefit. DATA SOURCES: Individual patient data from the Intensive Care National Audit & Research Centre Case Mix Programme were linked with the UK Renal Registry, Hospital Episode Statistics (for England), Patient Episodes Data for Wales and Civil Registrations (Deaths) data sets, and combined with identified periods of systemic heparin anticoagulation and regional citrate anticoagulation (survey of intensive care units). Staff time and consumables were obtained from micro-costing. Continuous renal replacement therapy system failures were estimated from the Post-Intensive Care Risk-adjusted Alerting and Monitoring data set. EuroQol-3 Dimensions, three-level version, health-related quality of life was obtained from the Intensive Care Outcomes Network study. RESULTS: Out of the 188 (94.9%) units that responded to the survey, 182 (96.8%) use continuous renal replacement therapy. After linkage, data were available from 69,001 patients across 181 intensive care units (60,416 during periods of systemic heparin anticoagulation use and 8585 during regional citrate anticoagulation use). The change to regional citrate anticoagulation was not associated with a step change in 90-day mortality (odds ratio 0.98, 95% confidence interval 0.89 to 1.08). Secondary outcomes showed step increases in days of renal support (difference in means 0.53 days, 95% confidence interval 0.28 to 0.79 days), advanced cardiovascular support (difference in means 0.23 days, 95% confidence interval 0.09 to 0.38 days) and advanced respiratory support (difference in means, 0.53 days, 95% CI 0.03 to 1.03 days) with a trend toward fewer bleeding episodes (odds ratio 0.90, 95% confidence interval 0.76 to 1.06) with transition to regional citrate anticoagulation. The micro-costing study indicated that regional citrate anticoagulation was more expensive and was associated with an estimated incremental net monetary loss (step change) of -£2376 (95% confidence interval -£3841 to -£911). The estimated likelihood of cost-effectiveness at 1 year was less than 0.1%. LIMITATIONS: Lack of patient-level treatment data means that the results represent average effects of changing to regional citrate anticoagulation in intensive care units. Administrative data are subject to variation in data quality over time, which may contribute to observed trends. CONCLUSIONS: The introduction of regional citrate anticoagulation has not improved outcomes for patients and is likely to have substantially increased costs. This study demonstrates the feasibility of evaluating effects of changes in practice using routinely collected data. FUTURE WORK: (1) Prioritise other changes in clinical practice for evaluation and (2) methodological research to understand potential implications of trends in data quality. TRIAL REGISTRATION: This trial is registered as ClinicalTrials.gov NCT03545750. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 26, No. 13. See the NIHR Journals Library website for further project information.

Acute kidney injury, which prevents kidneys from working properly, is common in critically ill patients being treated in an intensive care unit. Patients with acute kidney injury are treated with a machine that takes over kidney functions, a process called continuous renal replacement therapy. Traditionally, as part of continuous renal replacement therapy, heparin (an anticoagulant that stops the blood from clotting) is added to the blood as it enters the continuous renal replacement therapy machine. Recently, citrate anticoagulation (an alternative to heparin) has been increasingly used in intensive care units in the UK. However, the increased use of citrate is happening without evidence that this is better for patients and cost-effective for the NHS. We aimed to find out whether or not changing to citrate anticoagulation for continuous renal replacement therapy is more beneficial than heparin anticoagulation for patients with acute kidney injury treated in an intensive care unit. We also looked at whether or not changing to citrate is cost-effective for the NHS. We used routinely collected data from the Intensive Care National Audit & Research Centre Case Mix Programme national clinical audit to identify 69,001 patients who received continuous renal replacement therapy in an intensive care unit in England or Wales between 1 April 2009 and 31 March 2017. To get a more comprehensive view of the long-term effects of changing to citrate, we 'linked' data from the 69,001 patients together with other routinely collected data sets to get information on their hospital admissions, longer-term kidney problems and survival after leaving the intensive care unit. We combined this information with a survey of anticoagulant use in intensive care units in England and Wales to compare patients who received continuous renal replacement therapy with heparin and citrate. We found that the change to citrate was not associated with a significant change in the death rate at 90 days, but that it was more expensive for hospitals. Our findings suggest that the change to citrate-based anticoagulation may have been premature and should cause clinicians in intensive care units that are still using systemic heparin anticoagulation to pause before making this change.

ABM Clinical Protocol #35: Supporting Breastfeeding During Maternal or Child Hospitalization.

A central goal of the Academy of Breastfeeding Medicine is the development of clinical protocols for managing common medical problems that may impact breastfeeding success. These protocols serve only as guidelines for the care of breastfeeding mothers and infants and do not delineate an exclusive course of treatment or serve as standards of medical care. Variations in treatment may be appropriate according to the needs of an individual patient. The Academy of Breastfeeding Medicine recognizes that not all lactating individuals identify as female. Using gender-inclusive language, however, is not possible in all languages and all countries and for all readers. The position of the Academy of Breastfeeding Medicine (https://doi.org/10.1089/bfm.2021.29188.abm) is to interpret clinical protocols within the framework of inclusivity of all breastfeeding, chestfeeding, and human milk-feeding individuals.

Increasing awareness and uptake of the MenB vaccine on a large university campus.

Objective: At a large public university, we aimed to evaluate an intervention designed to increase serogroup B meningococcal (MenB) vaccine uptake and awareness.Methods: Using a pretest-posttest design with a double posttest, we evaluated an intervention conducted by a local foundation and the Florida Department of Health that distributed MenB vaccine on campus and conducted an educational campaign. Prior to intervention activities, we recruited students to complete a survey about their MenB knowledge and attitudes. For survey participants who provided contact information, we sent two follow-up surveys and assessed MenB vaccine records. We used chi-square tests, adjusted for nonindependence, to compare preintervention to postintervention (three-month and one-year) vaccination and attitudes.Results: Among the 686 students with accessible vaccine records, MenB vaccine initiation increased 9% (from 24% to 33%) and completion increased 8% (from 13% to 21%) from before the intervention to one year after the intervention. When restricting to students who completed the relevant follow-up surveys, the percentage of students who heard of the MenB vaccine increased by 15% (p > .001) from before the intervention to three months after (n = 188 students) and maintained a 10% increase (p > .001) one year after the intervention (n = 261 students). Among students that heard of the MenB vaccine, the percentage of students who thought they needed the MenB vaccine even though they received the MenACWY increased 14% (p = .03) by the three-month postintervention survey and up to 18% by the one-year follow-up (p = .002).Conclusions: A university-wide, on-campus vaccination and educational campaign increased college students' MenB vaccine initiation, completion, and knowledge.Clinicaltrials.gov ID: NCT02975596.

Evaluation of total inward leakage for NIOSH-approved elastomeric half-facepiece, full-facepiece, and powered air-purifying respirators using sodium chloride and corn oil aerosols.

Recently, total inward leakage (TIL) for filtering facepiece and elastomeric half-mask respirators (EHRs) was measured according to the International Organization for Standardization (ISO) test method standard 16900-1:2014 that showed larger TIL for corn oil aerosol than for NaCl aerosol. Comparison of TIL measured for different aerosols for higher protection level respirators is lacking. The objective of this study was to determine TIL for EHRs, full-facepiece respirators, and loose-fitting and tight-fitting powered air-purifying respirators (PAPRs) using NaCl and corn oil aerosols to compare. TIL was measured for two models each of EHRs, full-facepiece respirators, and loose-fitting and tight-fitting PAPRs. After fit testing with a PortaCount (TSI, St. Paul, MN) using the Occupational Safety and Health Administration (OSHA) protocol, eight subjects were tested in the NaCl aerosol chamber first and then in the corn oil aerosol chamber, while another eight subjects tested in the reverse order. Subjects were randomly assigned to one of the two groups. TIL was measured as a ratio of mass-based aerosol concentrations inside the mask to the test chamber while the subjects performed ISO 16900-1-defined exercises using continuous sampling methods. The concentration of corn oil aerosol was measured with one light scattering photometer, alternately, and NaCl aerosol was measured using two flame photometers. Results showed the geometric mean TIL for EHR was significantly (p < 0.05) larger for corn oil aerosol than for NaCl aerosol. EHR models equipped with P100 filters showed relatively smaller TIL values than the same models with N95 filters showing that TIL was inversely related to filter efficiency. Interestingly, TIL was significantly (p < 0.05) larger for NaCl aerosol than for corn oil aerosol for PAPRs, but not for full-facepiece respirators. TIL was inversely related to fit factors of respirator types. Overall, filter efficiency and faceseal leakage determine TIL. The relative trends in TIL for the two aerosols' test methods differ between respirator types indicating that generalization of TIL for respirator types may not be appropriate when using different test agents.

Residual Chlorine Induced Cationic Active Species on a Porous Copper Electrocatalyst for Highly Stable Electrochemical CO2 Reduction to C2.

Electrochemical carbon dioxide (CO2 ) reduction reaction (CO2 RR) is an attractive approach to deal with the emission of CO2 and to produce valuable fuels and chemicals in a carbon-neutral way. Many efforts have been devoted to boost the activity and selectivity of high-value multicarbon products (C2+ ) on Cu-based electrocatalysts. However, Cu-based CO2 RR electrocatalysts suffer from poor catalytic stability mainly due to the structural degradation and loss of active species under CO2 RR condition. To date, most reported Cu-based electrocatalysts present stabilities over dozens of hours, which limits the advance of Cu-based electrocatalysts for CO2 RR. Herein, a porous chlorine-doped Cu electrocatalyst exhibits high C2+ Faradaic efficiency (FE) of 53.8 % at -1.00 V versus reversible hydrogen electrode (VRHE ). Importantly, the catalyst exhibited an outstanding catalytic stability in long-term electrocatalysis over 240 h. Experimental results show that the chlorine-induced stable cationic Cu0 /Cu+ species and the well-preserved structure with abundant active sites are critical to the high FE of C2+ in the long-term run of electrochemical CO2 reduction.

Particle transfer and adherence to human skin compared with cotton glove and pre-moistened polyvinyl alcohol exposure sampling substrates.

Measurement of skin exposure to particles using interception (e.g., cotton gloves) and removal (e.g., wiping) sampling techniques could be inaccurate because these substrates do not have the same topography and adhesion characteristics as skin. The objective of this study was to compare particle transfer and adherence to cotton gloves, cotton gloves with artificial sebum, and a pre-moistened polyvinyl alcohol (PVA) material with bare human skin (fingertip, palm). Experiments were performed with aluminum oxide powder under standardized conditions for three types of surfaces touched, applied loads, contact times, and powder mass levels. In the final mixed model, the fixed effects of substrate, surface type, applied load, and powder mass and their significant two-way interaction terms explained 71% (transfer) and 74% (adherence) of the observed total variance in measurements. For particle mass transfer, compared with bare skin, bias was -77% (cotton glove with sebum) to +197% (PVA material) and for adherence bias ranged from -40% (cotton glove) to +428% (PVA material), which indicated under- and over-sampling by these substrates, respectively. Dermal exposure assessment would benefit from sampling substrates that better reflect human skin characteristics and more accurately estimate exposures. Mischaracterization of dermal exposure has important implications for exposure and risk assessment.

Does insulin resistance influence neurodegeneration in non-diabetic Alzheimer's subjects?

BACKGROUND: Type 2 diabetes is a risk factor for Alzheimer's disease (AD), and AD brain shows impaired insulin signalling. The role of peripheral insulin resistance on AD aetiopathogenesis in non-diabetic patients is still debated. Here we evaluated the influence of insulin resistance on brain glucose metabolism, grey matter volume and white matter lesions (WMLs) in non-diabetic AD subjects. METHODS: In total, 130 non-diabetic AD subjects underwent MRI and [18F]FDG PET scans with arterial cannula insertion for radioactivity measurement. T1 Volumetric and FLAIR sequences were acquired on a 3-T MRI scanner. These subjects also had measurement of glucose and insulin levels after a 4-h fast on the same day of the scan. Insulin resistance was calculated by the updated homeostatic model assessment (HOMA2). For [18F]FDG analysis, cerebral glucose metabolic rate (rCMRGlc) parametric images were generated using spectral analysis with arterial plasma input function. RESULTS: In this non-diabetic AD population, HOMA2 was negatively associated with hippocampal rCMRGlc, along with total grey matter volumes. No significant correlation was observed between HOMA2, hippocampal volume and WMLs. CONCLUSIONS: In non-diabetic AD, peripheral insulin resistance is independently associated with reduced hippocampal glucose metabolism and with lower grey matter volume, suggesting that peripheral insulin resistance might influence AD pathology by its action on cerebral glucose metabolism and on neurodegeneration.

Perceptions and Knowledge About the MenB Vaccine Among Parents of High School Students.

Serogroup B meningococcal disease (MenB) causes almost 60% of meningitis cases among adolescents and young adults. Yet, MenB vaccine coverage among adolescents remains below 10%. Since parents are the primary medical decision makers for adolescents, we examined MenB vaccination rates and parent attitudes about meningitis and the MenB vaccine. In 2018, in conjunction with a county-wide, school-based immunization campaign, we conducted a mixed methods study among parents of 16- to 17-year-olds. We facilitated focus groups asking parents about their knowledge of meningitis and reactions to educational materials and sent behavioral surveys based on Health Belief Model constructs to parents through the county high school system. Parents in three focus groups (n = 8; participation rate = 13%) expressed confusion about their child's need to receive the MenB vaccine in addition to the meningococcal conjugate vaccine (MenACWY), but conveyed strong trust in their physicians' recommendation. Among survey participants (n = 170), 70 (41%) had heard of the MenB vaccine. Among those 70 parents, the most common barriers to vaccination were concerns about side effects (55%) and uncertainty of susceptibility due to receipt of the MenACWY vaccine (30%). The percentage of teens that received at least one dose of the MenB vaccine was 50% (n = 35) by parent report and 23% (n = 16) by state vaccination records. Parents demonstrated uncertainty and confusion about the MenB vaccine particularly due to the existence of another meningitis vaccine and limited health care provider recommendations. Confirmatory studies of parent confusion about the MenB vaccine are needed to develop interventions.

Correction to: Evaluating the effects of the novel GLP-1 analogue liraglutide in Alzheimer's disease: study protocol for a randomised controlled trial (ELAD study).

An amendment to this paper has been published and can be accessed via the original article.

COVID-19 in Correctional and Detention Facilities - United States, February-April 2020.

An estimated 2.1 million U.S. adults are housed within approximately 5,000 correctional and detention facilities† on any given day (1). Many facilities face significant challenges in controlling the spread of highly infectious pathogens such as SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19). Such challenges include crowded dormitories, shared lavatories, limited medical and isolation resources, daily entry and exit of staff members and visitors, continual introduction of newly incarcerated or detained persons, and transport of incarcerated or detained persons in multiperson vehicles for court-related, medical, or security reasons (2,3). During April 22-28, 2020, aggregate data on COVID-19 cases were reported to CDC by 37 of 54 state and territorial health department jurisdictions. Thirty-two (86%) jurisdictions reported at least one laboratory-confirmed case from a total of 420 correctional and detention facilities. Among these facilities, COVID-19 was diagnosed in 4,893 incarcerated or detained persons and 2,778 facility staff members, resulting in 88 deaths in incarcerated or detained persons and 15 deaths among staff members. Prompt identification of COVID-19 cases and consistent application of prevention measures, such as symptom screening and quarantine, are critical to protecting incarcerated and detained persons and staff members.