Genotypic analysis of RTS,S/AS01E malaria vaccine efficacy against parasite infection as a function of dosage regimen and baseline malaria infection status in children aged 5-17 months in Ghana and Kenya: a longitudinal phase 2b randomised controlled trial.

BACKGROUND: The first licensed malaria vaccine, RTS,S/AS01E, confers moderate protection against symptomatic disease. Because many malaria infections are asymptomatic, we conducted a large-scale longitudinal parasite genotyping study of samples from a clinical trial exploring how vaccine dosing regimen affects vaccine efficacy. METHODS: Between Sept 28, 2017, and Sept 25, 2018, 1500 children aged 5-17 months were randomly assigned (1:1:1:1:1) to receive four different RTS,S/AS01E regimens or a rabies control vaccine in a phase 2b open-label clinical trial in Ghana and Kenya. Participants in the four RTS,S groups received two full doses at month 0 and month 1 and either full doses at month 2 and month 20 (group R012-20); full doses at month 2, month 14, month 26, and month 38 (group R012-14); fractional doses at month 2, month 14, month 26, and month 38 (group Fx012-14; early fourth dose); or fractional doses at month 7, month 20, and month 32 (group Fx017-20; delayed third dose). We evaluated the time to the first new genotypically detected infection and the total number of new infections during two follow-up periods (12 months and 20 months) in more than 36 000 dried blood spot specimens from 1500 participants. To study vaccine effects on time to the first new infection, we defined vaccine efficacy as one minus the hazard ratio (HR; RTS,S vs control) of the first new infection. We performed a post-hoc analysis of vaccine efficacy based on malaria infection status at first vaccination and force of infection by month 2. This trial (MAL-095) is registered with ClinicalTrials.gov, NCT03281291. FINDINGS: We observed significant and similar vaccine efficacy (25-43%; 95% CI union 9-53) against first new infection for all four RTS,S/AS01E regimens across both follow-up periods (12 months and 20 months). Each RTS,S/AS01E regimen significantly reduced the mean number of new infections in the 20-month follow-up period by 1·1-1·6 infections (95% CI union 0·6-2·1). Vaccine efficacy against first new infection was significantly higher in participants who were infected with malaria (68%; 95% CI 50-80) than in those who were uninfected (37%; 23-48) at the first vaccination (p=0·0053). INTERPRETATION: All tested dosing regimens blocked some infections to a similar degree. Improved vaccine efficacy in participants infected during vaccination could suggest new strategies for highly efficacious malaria vaccine development and implementation. FUNDING: GlaxoSmithKline Biologicals SA, PATH, Bill & Melinda Gates Foundation, and the German Federal Ministry of Education and Research.

Could less be more? Accounting for fractional-dose regimens and different number of vaccine doses when measuring the impact of the RTS, S/AS01E malaria vaccine.

BACKGROUND: The RTS, S/AS01E malaria vaccine (RTS, S) is recommended for children in moderate-to-high Plasmodium falciparum malaria transmission areas. This phase 2b trial (NCT03276962) evaluates RTS, S fractional- and full-dose regimens in Ghana and Kenya. METHODS: 1500 children aged 5-17 months were randomised (1:1:1:1:1) to receive RTS, S or rabies control vaccine. RTS, S groups received two full RTS, S doses at month (M)0/M1 followed by either full (groups R012-20, R012-14-26) or fractional (1/5) doses (groups Fx012-14-26, Fx017-20-32). RESULTS: At M32 post-first dose, vaccine efficacy (VE) against clinical malaria (all episodes) ranged from 38% (R012-20; 95%CI: 24-49) to 53% (R012-14-26; 95%CI: 42-62). Vaccine impact estimates (cumulative number of malaria cases averted/1000 children vaccinated) were 1344 (R012-20), 2450 (R012-14-26), 2273 (Fx012-14-26), 2112 (Fx017-20-32). To account for differences in vaccine volume (fractional- versus full-dose), in a post-hoc analysis, we also estimated cases averted/1000 RTS, S full-dose equivalents: 336 (R012-20), 490 (R012-14-26), 874 (Fx012-14-26), 880 (Fx017-20-32). CONCLUSIONS: VE against clinical malaria was similar in all RTS, S groups. Vaccine impact accounting for full-dose equivalence suggests that using fractional-dose regimens could be a viable dose-sparing strategy. If borne out through trial end (M50), these observations underscore the means to reduce cost per regimen with a goal of maximising impact and optimising supply.

Neonatal Dermatopathology: A 10-Year Institutional Review.

BACKGROUND/OBJECTIVE: Neonatal skin conditions are typically diagnosed through noninvasive methods. Few studies describe the spectrum of biopsy- evaluated neonatal skin lesions. We present our institutional experience with the conditions leading to skin biopsies in neonates. The objective is to describe the conditions for which skin biopsies are performed in neonatal patients. METHODS: There were 20 neonatal skin biopsies over a 10-year period from the hospital's delivery unit, NICU, and pediatric hospital. Biopsies were categorized as inflammatory (not caused by an infectious agent), congenital, neoplastic, infectious, and vascular conditions. RESULTS: The patients' ages ranged from 1 day to 4 weeks, with a male predominance. There were 6 inflammatory, 7 congenital, 5 neoplastic, 1 infectious, and 1 vascular lesions. CONCLUSIONS: The most frequent neonatal skin biopsy lesions were inflammatory or congenital lesions. This review described the types of neonatal dermatopathology specimens that we encountered in practice.

Association between depressive symptoms and dynamic balance among young adults in the community.

Background: Detecting and addressing depression symptoms at their outset can reduce the burden on individuals and society; however, it has a limitation in that such evaluations mainly rely on self-reports. Several studies have demonstrated a strong association between motor symptoms and early depression. We aimed to associate body balance measured by the Lower Quarter Y Balance Test (YBT-LQ) with depressive symptoms among young adults in the community, to confirm the current evidence that depression negatively influences body balance. Research question: Is the YBT-LQ an objective tool for measuring and evaluating young adults' depression risks, as well as assessing whether depression negatively influences body balance? Methods: Our participants comprised 36 young adults. We assessed their depressive symptoms using the Center for Epidemiological Studies Depression Scale (CES-D) via a Google survey, measured their body balance with the YBT-LQ, and analyzed data with Spearman's rank-order correlation coefficient test, using SPSS version 27.0. Results: We found that the right leg's anterior, posteromedial, and posterolateral scores- Z = -2.129, p = .033; Z = -2.181, p = .029; and Z = -2.250, p = .024, respectively-and composite scores-Z = 73.00, p = .027 -were significantly lower in the group with risk for clinical depression compared to the normal group. The CES-D total score had a negative association with all YBT-LQ scores, except for the anterior score of the left leg. Among the CES-D sub-factors, somatic and retarded activity showed negative correlations with all the YBT-LQ scores. Significance: Our findings revealed that depressive symptoms have a negative association with balance, and that the YBT-LQ can be a reliable tool for measuring motor symptoms of depression, specifically among young adults.

Seasonal vaccination with RTS,S/AS01E vaccine with or without seasonal malaria chemoprevention in children up to the age of 5 years in Burkina Faso and Mali: a double-blind, randomised, controlled, phase 3 trial.

BACKGROUND: Seasonal vaccination with the RTS,S/AS01E vaccine combined with seasonal malaria chemoprevention (SMC) prevented malaria in young children more effectively than either intervention given alone over a 3 year period. The objective of this study was to establish whether the added protection provided by the combination could be sustained for a further 2 years. METHODS: This was a double-blind, individually randomised, controlled, non-inferiority and superiority, phase 3 trial done at two sites: the Bougouni district and neighbouring areas in Mali and Houndé district, Burkina Faso. Children who had been enrolled in the initial 3-year trial when aged 5-17 months were initially randomly assigned individually to receive SMC with sulphadoxine-pyrimethamine and amodiaquine plus control vaccines, RTS,S/AS01E plus placebo SMC, or SMC plus RTS,S/AS01E. They continued to receive the same interventions until the age of 5 years. The primary trial endpoint was the incidence of clinical malaria over the 5-year trial period in both the modified intention-to-treat and per-protocol populations. Over the 5-year period, non-inferiority was defined as a 20% increase in clinical malaria in the RTS,S/AS01E-alone group compared with the SMC alone group. Superiority was defined as a 12% difference in the incidence of clinical malaria between the combined and single intervention groups. The study is registered with ClinicalTrials.gov, NCT04319380, and is complete. FINDINGS: In April, 2020, of 6861 children originally recruited, 5098 (94%) of the 5433 children who completed the initial 3-year follow-up were re-enrolled in the extension study. Over 5 years, the incidence of clinical malaria per 1000 person-years at risk was 313 in the SMC alone group, 320 in the RTS,S/AS01E-alone group, and 133 in the combined group. The combination of RTS,S/AS01E and SMC was superior to SMC (protective efficacy 57·7%, 95% CI 53·3 to 61·7) and to RTS,S/AS01E (protective efficacy 59·0%, 54·7 to 62·8) in preventing clinical malaria. RTS,S/AS01E was non-inferior to SMC (hazard ratio 1·03 [95% CI 0·95 to 1·12]). The protective efficacy of the combination versus SMC over the 5-year period of the study was very similar to that seen in the first 3 years with the protective efficacy of the combination versus SMC being 57·7% (53·3 to 61·7) and versus RTS/AS01E-alone being 59·0% (54·7 to 62·8). The comparable figures for the first 3 years of the study were 62·8% (58·4 to 66·8) and 59·6% (54·7 to 64·0%), respectively. Hospital admissions for WHO-defined severe malaria were reduced by 66·8% (95% CI 40·3 to 81·5), for malarial anaemia by 65·9% (34·1 to 82·4), for blood transfusion by 68·1% (32·6 to 84·9), for all-cause deaths by 44·5% (2·8 to 68·3), for deaths excluding external causes or surgery by 41·1% (-9·2 to 68·3), and for deaths from malaria by 66·8% (-2·7 to 89·3) in the combined group compared with the SMC alone group. No safety signals were detected. INTERPRETATION: Substantial protection against malaria was sustained over 5 years by combining seasonal malaria vaccination with seasonal chemoprevention, offering a potential new approach to malaria control in areas with seasonal malaria transmission. FUNDING: UK Joint Global Health Trials and PATH's Malaria Vaccine Initiative (through a grant from the Bill & Melinda Gates Foundation). TRANSLATION: For the French translation of the abstract see Supplementary Materials section.

Baseline malaria infection status and RTS,S/AS01E malaria vaccine efficacy.

Background: The only licensed malaria vaccine, RTS,S/AS01 E , confers moderate protection against symptomatic disease. Because many malaria infections are asymptomatic, we conducted a large-scale longitudinal parasite genotyping study of samples from a clinical trial exploring how vaccine dosing regimen affects vaccine efficacy (VE). Methods: 1,500 children aged 5-17 months were randomized to receive four different RTS,S/AS01 E regimens or a rabies control vaccine in a phase 2b clinical trial in Ghana and Kenya. We evaluated the time to the first new genotypically detected infection and the total number of new infections during two follow-up periods in over 36K participant specimens. We performed a post hoc analysis of VE based on malaria infection status at first vaccination and force of infection. Results: We observed significant and comparable VE (25-43%, 95% CI union 9-53%) against first new infection for all four RTS,S/AS01 E regimens across both follow-up periods (12 and 20 months). Each RTS,S/AS01 E regimen significantly reduced the number of new infections in the 20-month follow-up period (control mean 4.1 vs. RTS,S/AS01 E mean 2.6-3.0). VE against first new infection was significantly higher in participants who were malaria-infected (68%; 95% CI, 50 to 80%) versus uninfected (37%; 95% CI, 23 to 48%) at the first vaccination (P=0.0053) and in participants experiencing greater force of infection between dose 1 and 3 (P=0.059). Conclusions: All tested dosing regimens blocked some infections to a similar degree. Improved VE in participants infected during vaccination could suggest new strategies for highly efficacious malaria vaccine development and implementation. ( ClinicalTrials.gov number, NCT03276962 ).

Disadvantaged Students Utilize School Campus and Its Resources More Than Non-disadvantaged Students.

Introduction Disadvantaged populations were disproportionately affected by the COVID-19 pandemic, both in the medical and educational settings. Lower-income families often do not have a laptop/desktop computer, adequate internet connection, or a dedicated study space. This unfortunately contributed to poorer academic performance during distance learning. To combat this, the Kirk Kerkorian School of Medicine (KKSOM) did not close down campus during the pandemic. This study analyzes the utilization of campus and live Zoom lectures by KKSOM students and its impact on educational outcomes. Methods We sent an Institutional Review Board (IRB)-approved survey to KKSOM students and asked about study locations, Zoom lecture attendance, and relationship quality during the pandemic. The class of 2024 had a unique experience as they were first-year students during the start of the COVID-19 pandemic and the transition to online learning. However, they always had access to campus and technological resources. We compared the survey scores from a Qualtrics electronic survey and the National Board of Medical Examiners (NBME) scores of students who self-indicated disadvantaged status, first-generation, underrepresented minority, and lower socioeconomic status to those who did not meet these criteria. Data analysis was done using SPSS software version 28.0.1.1 (IBM Corp., Armonk, NY). Results  First-generation students studied on campus more frequently than their counterparts (31% versus 20%, p < 0.05) and less at home in general (55.4% versus 67.5%, p < 0.05). Lower socioeconomic status (SES) students attended live Zoom lectures more often as well (56.6% versus 43.1%, p < 0.05). Lastly, no significant differences were found between disadvantaged and non-disadvantaged groups for the class of 2024 in the NBME exam scores or relationship quality scores. Conclusion Our results suggest that students from disadvantaged backgrounds spend more time studying on campus than at home. Additionally, during the COVID-19 pandemic, they attended live Zoom lectures more often than their non-disadvantaged counterparts. Access to campus was not restricted for KKSOM students during the pandemic. This may be one explanation for the lack of disparity between disadvantaged and non-disadvantaged students with regard to academic performance and relationship quality. This makes a strong argument for the importance of campus accessibility for the success of students, especially those from disadvantaged backgrounds.

Use of GPT-4 to Analyze Medical Records of Patients With Extensive Investigations and Delayed Diagnosis.

This case series investigates whether analysis of clinical history via a language model system improves diagnostic accuracy in patients with complex and delayed diagnoses.

Cost of introducing and delivering malaria vaccine (RTS,S/AS01E) in areas of seasonal malaria transmission, Mali and Burkina Faso.

BACKGROUND: The WHO recommends use of the RTS,S/AS01E (RTS,S) malaria vaccine for young children living in areas of moderate to high Plasmodium falciparum malaria transmission and suggests countries consider seasonal vaccination in areas with highly seasonal malaria. Seasonal vaccination is uncommon and may require adaptations with potential cost consequences. This study prospectively estimates cost of seasonal malaria vaccine delivery in Mali and Burkina Faso. METHODS: Three scenarios for seasonal vaccine delivery are costed (1) mass campaign only, (2) routine Expanded Programme on Immunisation (EPI) and (3) mixed delivery (mass campaign and routine EPI)), from the government's perspective. Resource use data are informed by previous new vaccine introductions, supplemented with primary data from a sample of health facilities and administrative units. FINDINGS: At an assumed vaccine price of US $5 per dose, the economic cost per dose administered ranges between $7.73 and $8.68 (mass campaign), $7.04 and $7.38 (routine EPI) and $7.26 and $7.93 (mixed delivery). Excluding commodities, the cost ranges between $1.17 and $2.12 (mass campaign), $0.48 and $0.82 (routine EPI) and $0.70 and $1.37 (mixed delivery). The financial non-commodity cost per dose administered ranges between $0.99 and $1.99 (mass campaign), $0.39 and $0.76 (routine EPI) and $0.58 and $1.28 (mixed delivery). Excluding commodity costs, service delivery is the main cost driver under the mass campaign scenario, accounting for 36% to 55% of the financial cost. Service delivery accounts for 2%-8% and 12%-23% of the total financial cost under routine EPI and mixed delivery scenarios, respectively. CONCLUSION: Vaccine delivery using the mass campaign approach is most costly followed by mixed delivery and routine EPI delivery approaches, in both countries. Our cost estimates provide useful insights for decisions regarding delivery approaches, as countries plan the malaria vaccine rollout.

Opioid-Modulated Receptor Localization and Erk1/2 Phosphorylation in Cells Coexpressing µ-Opioid and Nociceptin Receptors.

We attempted to examine the alterations elicited by opioids via coexpressed µ-opioid (MOP) and nociceptin/orphanin FQ (NOP) receptors for receptor localization and Erk1/2 (p44/42 MAPK) in human embryonic kidney (HEK) 293 cells. Through two-photon microscopy, the proximity of MOP and NOP receptors was verified by fluorescence resonance energy transfer (FRET), and morphine but not buprenorphine facilitated the process of MOP-NOP heterodimerization. Single-particle tracking (SPT) further revealed that morphine or buprenorphine hindered the movement of the MOP-NOP heterodimers. After exposure to morphine or buprenorphine, receptor localization on lipid rafts was detected by immunocytochemistry, and phosphorylation of Erk1/2 was determined by immunoblotting in HEK 293 cells expressing MOP, NOP, or MOP+NOP receptors. Colocalization of MOP and NOP on lipid rafts was enhanced by morphine but not buprenorphine. Morphine stimulated the phosphorylation of Erk1/2 with a similar potency in HEK 293 cells expressing MOP and MOP+NOP receptors, but buprenorphine appeared to activate Erk1/2 solely through NOP receptors. Our results suggest that opioids can fine-tune the cellular localization of opioid receptors and phosphorylation of Erk1/2 in MOP+NOP-expressing cells.

Feeling possessive, performing well? Effects of job-based psychological ownership on territoriality, information exchange, and job performance.

Job-based psychological ownership arises when workers develop personal feelings of possession over various aspects of a job. Drawing on conservation of resources and regulatory focus theory, the current research adopts a resource-based perspective to suggest a double-edged effect on job performance, mediated by three forms of territoriality (marking, defending, expanding) and information exchange and moderated by individual regulatory focus. With a multistep process in Study 1, the authors develop and validate a territorial expanding scale. Among 358 employee-supervisor dyads, Study 2 tests the proposed model; job-based psychological ownership prompts employees to engage in territorial marking, defending, and expanding. Territorial defending correlates negatively with information exchange, territorial expanding is positively related to it, and territorial marking has no relationship with information exchange. Information exchange is positively related to job performance. Job-based psychological ownership impedes job performance through increased territorial defending and reduced information exchange, especially among employees with a prevention focus. It enhances job performance through increased territorial expanding and increased information exchange, particularly if employees have a high promotion focus. These findings have notable implications for research and practice. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Reduced mortality in patients with extended duration of methadone maintenance treatment: a five-year retrospective nationwide study.

BACKGROUND: The retention of patients under methadone maintenance treatment (MMT) is an indication for the effectiveness of the therapy. We aimed to explore the relation between mortality and the cumulative MMT duration. METHODS: A retrospective cohort analysis was performed using Taiwan Illicit Drug Issue Database (TIDID) and National Health Insurance Research Database (NHIRD) during 2012-2016. We included 9149 and 11 112 MMT patients as the short and long groups according to the length of their cumulative MMT duration, 1-364 and ⩾365 days, respectively. The risk of mortality was calculated by Cox proportional hazards regression model with time-dependent exposure to MMT, and the survival probability was plotted with the Kaplan-Meier curve. RESULTS: The mortality rates were 2.51 and 1.51 per 100 person-years in the short and long cumulative MMT duration groups, respectively. After adjusting for on or off MMT, age, sex, marital status, education level, maximum methadone dose, and comorbidities (human immunodeficiency virus, depression, hepatitis C virus, hepatitis B virus, alcoholic liver disease, and cardiovascular disease), the long group had a lower risk of death (hazard ratio = 0.67; 95% confidence interval 0.60-0.75) than the short group. Increased risk was observed in patients with advanced age, being male, unmarried, infected by HIV, HCV, and HBV, and diagnosed with depression, ALD, and CVD. Causes of death were frequently related to drug and injury. CONCLUSIONS: Longer cumulative MMT duration is associated with lower all-cause and drug-related mortality rate.

Exploration of the Role of Relationships and Virtual Learning on Academic Performance and Mental Health.

Background The coronavirus disease 2019 (COVID-19) pandemic caused medical schools to rapidly transition to online/distance learning. Online learning is often associated with poor academic performance, mental health, and student-to-faculty relationships. The purpose of this study is to determine if correlations exist between academic performance, mental health, study location, and student/faculty relationships among medical students. Methodology First-year medical students received a survey asking them to reflect on their study location, mental health, and student/faculty relationships during the COVID-19 pandemic. Second- and third-year medical students received a similar survey asking them to reflect on their experiences from the perspective of their first year of medical school (pre-pandemic). The first five exam scores were gathered for all participants. Pearson's correlation coefficient was calculated between all variables. Results Academic performance was found to be positively correlated with both mental health (R = 0.215, p = 0.016) and relationships among students (R = 0.0259, p = 0.004), while negatively correlated with the percentage of time spent studying at home (R = -0.185, p = 0.039). Mental health was additionally found to be positively correlated with relationships to faculty (R = 0.230, p = 0.01) and relationships to students (R = 0.245, p = 0.006). Conclusions Academic performance and mental health are correlated with relationships and study location. These correlations may explain the negative outcomes associated with online learning in medical education.

Evaluation of the potential of Rejuveinix plus dexamethasone against sepsis.

Aim: Our main objectives were to compare the effects of Rejuveinix (RJX), dexamethasone (DEX) and their combination on the severity of sepsis and survival outcome in an animal model of fatal sepsis. Methods: We used the LPS plus D-galactosamine mouse model of sepsis to compare the anti-inflammatory activities of RJX, dexamethasone and a combination of RJX plus DEX. Additionally, we examined the clinical feasibility and tolerability of combining RJX with DEX in COVID-19 patients in a clinical phase I study. Data were analyzed using standard methods. Results & conclusion: RJX exhibited potent anti-inflammatory activity in the murine sepsis model. The combination of RJX plus DEX was more effective than either agent alone, decreased the inflammatory cytokine responses and associated organ damage, and improved the survival outcome in mice. In the phase I clinical study, RJX plus DEX was well tolerated by COVID-19 patients.

Digital Strategies to Accelerate Help-Seeking in Youth With Psychiatric Concerns in New York State.

Background: Mental illness in transition age youth is common and treatment initiation is often delayed. Youth overwhelmingly report utilizing the Internet to gather information while psychiatric symptoms emerge, however, most are not yet ready to receive a referral to care, forestalling the established benefit of early intervention. Methods: A digital outreach campaign and interactive online care navigation platform was developed and deployed in New York State on October 22, 2020. The campaign offers live connection to a peer or counselor, a self-assessment mental health quiz, and educational material all designed to promote help-seeking in youth and their allies. Results: Between October 22, 2020 and July 31, 2021, the campaign resulted in 581,981 ad impressions, 16,665 (2.9%) clicks, and 13,717 (2.4%) unique website visitors. A third (4,562, 33.2%) completed the quiz and 793 (0.1%) left contact information. Of those, 173 (21.8%) completed a virtual assessment and 155 (19.5%) resulted in a referral to care. The median age of those referred was 21 years (IQR = 11) and 40% were considered to be from low-income areas. Among quiz completers, youth endorsing symptoms of depression or anxiety were more likely to leave contact information (OR = 2.18, 95% CI [1.39, 3.41] and OR = 1.69, 95% CI [1.31, 2.19], respectively) compared to those not reporting symptoms of depression or anxiety. Youth endorsing symptoms of psychosis were less likely to report a desire to receive a referral to care (OR = 0.58, 95% CI [0.43, 0.80]) compared to those who did not endorse symptoms of psychosis. Conclusion: Self-reported symptomatology impact trajectories to care, even at the earliest stages of help-seeking, while youth and their allies are searching for information online. An online care navigation team could serve as an important resource for individuals with emerging behavioral health concerns and help to guide the transition between online information seeking at baseline to care.

Efficacy of RTS,S/AS01E malaria vaccine administered according to different full, fractional, and delayed third or early fourth dose regimens in children aged 5-17 months in Ghana and Kenya: an open-label, phase 2b, randomised controlled trial.

BACKGROUND: Controlled infection studies in malaria-naive adults suggest increased vaccine efficacy for fractional-dose versus full-dose regimens of RTS,S/AS01. We report first results of an ongoing trial assessing different fractional-dose regimens in children, in natural exposure settings. METHODS: This open-label, phase 2b, randomised controlled trial is conducted at the Malaria Research Center, Agogo, Ashanti Region (Ghana), and the Kenya Medical Research Institute and the US Centers for Disease Control and Prevention site in Siaya County (Kenya). We enrolled children aged 5-17 months without serious acute or chronic illness who had previously received three doses of diphtheria, tetanus, pertussis, and hepatitis B vaccine and at least three doses of oral polio vaccine. Children were randomly assigned (1:1:1:1:1) using a web-based randomisation system with a minimisation procedure accounting for centre to receive rabies control vaccine (M012 schedule) or two full doses of RTS,S/AS01E at month 0 and month 1, followed by either full doses at months 2 and 20 (group R012-20 [standard regimen]), full doses at months 2, 14, 26, and 38 (R012-14), fractional doses at months 2, 14, 26, and 38 (Fx012-14), or fractional doses at months 7, 20, and 32 (Fx017-20). The fractional doses were administered as one fifth (0·1 mL) of the full RTS,S dose (0·5 mL) after reconstitution. All vaccines were administered by intramuscular injection in the left deltoid. The primary outcome was occurrence of clinical malaria cases from month 2·5 until month 14 for the Fx012-14 group versus the pooled R012-14 and R012-20 groups in the per-protocol set. We assessed incremental vaccine efficacy of the Fx012-14 group versus the pooled R012-14 and R012-20 group over 12 months after dose three. Safety was assessed in all children who received at least one vaccine dose. This trial is registered with ClinicalTrials.gov, NCT03276962. FINDINGS: Between Sept 28, 2017, and Sept 25, 2018, 2157 children were enrolled, of whom 1609 were randomly assigned to a treatment group (322 to each RTS,S/AS01E group and 321 to the rabies vaccine control group). 1500 children received at least one study vaccine dose and the per-protocol set comprised 1332 children. Over 12 months after dose three, the incremental vaccine efficacy in the Fx012-14 group versus the pooled R012-14 and R12-20 groups was -21% (95% CI -57 to 7; p=0·15). Up to month 21, serious adverse events occurred in 48 (16%) of 298 children in the R012-20 group, 45 (15%) of 294 in the R012-14 group, 47 (15%) of 304 in the Fx012-14 group, 62 (20%) of 311 in the Fx017-20 group, and 71 (24%) of 293 in the control group, with no safety signals observed. INTERPRETATION: The Fx012-14 regimen was not superior to the standard regimen over 12 months after dose three. All RTS,S/AS01E regimens provided substantial, similar protection against clinical malaria, suggesting potential flexibility in the recommended dosing regimen and schedule. This, and the effect of annual boosters, will be further evaluated through 50 months of follow-up. FUNDING: GlaxoSmithKline Biologicals; PATH's Malaria Vaccine Initiative.

The Impact of COVID-19 on Academic Performance and Personal Experience Among First-Year Medical Students.

Background: The COVID-19 pandemic forced medical education to rapidly transition from in-person learning to online learning. This change came with learning difficulties, social isolation, limited student/faculty relationships, and decreased academic performance. Objective: The purpose of this study is to determine if academic performance, study habits, student/faculty relationships, and mental health were different in first-year medical students (class of 2024) during the COVID-19 pandemic compared to pre-COVID cohorts. Methods: In April 2021, a survey was sent to first-year medical students at the Kirk Kerkorian School of Medicine at UNLV asking them to reflect on their experiences during the COVID-19 pandemic including study environment, mental health, and relationships with peers and faculty. A similar survey was sent to second- and third-year medical students (classes of 2023 and 2022) asking them to reflect on similar experiences during their first year of medical school. Exam scores for the first five exams were gathered and compared between first-, second-, and third-year medical students. Results: One hundred twenty-five students responded to the survey (81% of first-year students, 75% of second-year students, and 55% of third-year students). During the COVID-19 pandemic, first semester students did not score above the national average as much as first semester students pre-COVID (55% vs. 77%). Students during the pandemic studied at home more than previous cohorts. Mental health and relationships were all rated significantly lower among first semester students during the COVID-19 pandemic. Conclusions: Significant differences were found in first semester student experience and academic performance during the pandemic compared to pre-COVID cohorts.

Disaster or opportunity? How COVID-19-associated changes in environmental uncertainty and job insecurity relate to organizational identification and performance.

The coronavirus disease 2019 (COVID-19) pandemic continues to create tremendous uncertainty in workplaces. Building on a social identity perspective, this study develops and tests a model of how and why COVID-19-associated uncertainty affects employee work outcomes. The model differentiates uncertainty as either internal (job insecurity) or external (perceived environmental uncertainty) to the organization and reveals their different effects on employee organizational identification, which positively affects employee work outcomes (work effort, organizational citizenship behavior, and performance). With a latent change score to model intraindividual changes, we found that increases (or decreases) in job insecurity before versus during the pandemic related to subsequent decreases (or increases) in organizational identification, whereas increases (or decreases) in perceived environmental uncertainty before versus during the pandemic related to subsequent increases (or decreases) in organizational identification; increases (or decreases) in organizational identification then related to increases (or decreases) in positive work outcomes. These findings complement existing theoretical views that uncertainty typically leads to poor performance by inducing anxiety, and that organizational identification suffers during a crisis such as COVID-19. In turn, this research offers practical implications to help organizations avoid discouraging and even encourage greater organizational identification and performance during crises. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Risk of psychosis in illicit amphetamine users: a 10 year retrospective cohort study.

QUESTION: Amphetamine use is a risk factor for psychosis, which imposes a substantial burden on society. We aimed to investigate the incidence of psychosis associated with illicit amphetamine use and whether rehabilitation treatments could influence the psychosis risk. STUDY SELECTION AND ANALYSIS: A retrospective cohort study was conducted using the population based Taiwan Illicit Drug Issue Database (TIDID) and the National Health Insurance Research Database (NHIRD), from 2007 to 2016. We identified 74 601 illicit amphetamine users as the amphetamine cohort and 2 98 404 subjects as the non-amphetamine cohort. The incidence rate of newly diagnosed psychosis was the main outcome. Cox proportional hazards models were applied to assess the effects of amphetamine, and the Kaplan-Meier method was used to estimate the cumulative psychosis incidence curves. FINDINGS: Illicit amphetamine users were 5.28 times more likely to experience psychosis than those without illicit drug use records. The risk was higher for subjects with multiple arrests for amphetamine use. A greater hazard ratio (HR) magnitude was observed in female patients. We also observed a significant decrease in the risk of psychosis in patients receiving rehabilitation treatments during deferred prosecution (adjusted HR 0.74, 95% CI 0.61 to 0.89). CONCLUSIONS: Illicit amphetamine use was associated with an increased incidence of psychosis. The risk was identified across all age groups, particularly in women and in those arrested multiple times, and was inversely correlated with rehabilitation treatments for amphetamine misuse.