Immune and behavioral correlates of protection against symptomatic post-vaccination SARS-CoV-2 infection.

Introduction: We sought to determine pre-infection correlates of protection against SARS-CoV-2 post-vaccine inzfections (PVI) acquired during the first Omicron wave in the United States. Methods: Serum and saliva samples from 176 vaccinated adults were collected from October to December of 2021, immediately before the Omicron wave, and assessed for SARS-CoV-2 Spike-specific IgG and IgA binding antibodies (bAb). Sera were also assessed for bAb using commercial assays, and for neutralization activity against several SARS-CoV-2 variants. PVI duration and severity, as well as risk and precautionary behaviors, were assessed by questionnaires. Results: Serum anti-Spike IgG levels assessed by research assay, neutralization titers against Omicron subvariants, and low home risk scores correlated with protection against PVIs after multivariable regression analysis. Commercial assays did not perform as well as research assay, likely due to their lower dynamic range. Discussion: In the 32 participants that developed PVI, anti-Spike IgG bAbs correlated with lower disease severity and shorter duration of illness.

Seasonal pattern of questing ticks and prevalence of pathogenic Rickettsia and Anaplasmataceae in Khao Yai national park, Thailand.

BACKGROUND: Tick-borne diseases (TBD) are considered neglected diseases in Thailand with disease burden likely underestimated. To assess risk for emerging TBD in Thailand, the seasonality of questing tick and pathogen prevalence were studied in Khao Yai National Park, a top tourist destination. METHODS: During 2019, questing ticks around tourist attractions were systematically collected bimonthly and analyzed for Rickettsia and Anaplasmataceae bacterial species by polymerase chain reaction and DNA sequencing. RESULTS: Larvae and nymphs of questing ticks peaked in Khao Yai National Park during the late rainy-winter season, though no specific trends were observed in adult ticks. Winter (November to February) was the highest risk for human tick-bites due to higher numbers of both ticks and visitors. Of the total 5916 ticks analyzed (651 pools), Anaplasma phagocytophilum, Neoehrlichia mikurensis, Ehrlichia ewingii, and Ehrlichia chaffeensis were detected at low rates (≤0.05%). There was a higher prevalence of human rickettsioses (0.2-7%) in ticks surveyed with Rickettsia tamurae, Rickettsia raoultii, and Rickettsia montana the major species. Amblyomma ticks had the highest prevalence of Rickettsia (85%, 35/44 Amblyomma adults), in which only R. tamurae and R. raoultii were found in Amblyomma with mixed species infections common. We report the first detection of R. africae-like and N. mikurensis in Ixodes granulatus adults in Thailand, suggesting I. granulatus as a potential vector for these pathogens. CONCLUSION: This study demonstrated the risk of emerging TBD in Thailand and underscores the need for tick-bite prevention among tourists in Thailand.

Assessing Clinical Utility of Pharmacogenetic Testing in the Military Health System.

INTRODUCTION: Response to medications can differ widely among individual patients. Adverse drug reactions can lead to serious morbidity and mortality. Pharmacogenetic (PGx) testing can predict responses to medications and increased risks of adverse events where the genetic basis is understood. Several published manuscripts suggest positive impacts of systematic preemptive PGx testing. However, few studies have been conducted on PGx implementation in the Military Health System (MHS). MATERIAL AND METHODS: A cross-sectional study of adult beneficiaries in a primary care clinic at a large military treatment facility was conducted in 2022. Participants underwent PGx genotyping of CYP2C19 and CYP2D6 genes at the Defense Health Agency Genetics Reference Laboratory. Participant medication lists were compared to the current Clinical Pharmacogenetic Implementation Consortium (CPIC) PGx gene-drug guidelines to assess potential actionability of these results. RESULTS: Genotyping of CYP2C19 and CYP2D6 in 165 MHS beneficiaries (mean age: 65 years) revealed that 81.2% of participants had at least one abnormal PGx finding. Among those with an abnormal PGx result, 65% were taking a medication listed on the CPIC website with an association with the particular gene in which the finding was identified. In addition, 78% of all of the participants in the study were taking at least one medication that is metabolized by CYP2C19 or CYP2D6 with associated CPIC guidelines. CONCLUSIONS: Pharmacogenetic testing for CYP2C19 and CYP2D6 identified a substantial proportion of MHS patients at a single center who could benefit from evaluation of current medication regimens based on the CPIC guidelines. Individualized medical management may be warranted to a greater degree than previously recognized based on the findings given possible differences in medication metabolism. Many MHS beneficiaries already take medications metabolized by CYP2C19 and CYP2D6, and a substantial proportion may be at risk for preventable adverse events for medications metabolized by these enzymes. While preliminary, a large number of actionable polymorphisms among a relatively small set of individuals taking at-risk medications suggest that implementing PGx testing in clinical practice may be beneficial in the MHS with appropriate clinical infrastructure.

Sociocultural Risk and Resilience in the Context of Adverse Childhood Experiences.

Importance: Knowledge about childhood resilience factors relevant in circumstances of marginalization and high numbers of adverse childhood experiences (ACEs) can improve interventions. Objective: To identify sociocultural resilience factors in childhood that are associated with better young adult mental health in the context of ACEs. Design, Setting, and Participants: This cohort study examined 4 waves of data from the Boricua Youth Study, which included Puerto Rican children from the South Bronx, New York, and San Juan, Puerto Rico. Participants were aged 5 to 17 years at waves 1 through 3 (2000-2003) and aged 15 to 29 years at wave 4 (2013-2017). Linear and logistic regression models tested the associations of 7 childhood resilience factors and their interaction with ACEs on young adult mental health outcomes. Data were analyzed from June 2021 to October 2023. Main Outcomes and Measures: Perceived stress, major depressive disorder and/or generalized anxiety disorder (MDD/GAD), and substance use disorder (SUD) in young adulthood. Results: Among a total 2004 participants, the mean (SD) age at wave 4 was 22.4 (2.9) years; 1024 participants (51.1%) were female, and 980 (48.9%) were male. Positive parent-child relationships and nonparental adult support during childhood were associated with both lower perceived stress (ß = -0.14; SE = 0.02; P < .001; ß = -0.08; SE = 0.03; P = .003, respectively) and lower odds of MDD/GAD (adjusted odds ratio [aOR], 0.84; 95% CI, 0.73 to 0.97; aOR = 0.81; 95% CI, 0.69 to 0.95, respectively) in young adulthood. Maternal warmth reported during childhood was also associated with lower young adult perceived stress (ß = -0.11; SE = 0.02; P < .001). None of the resilience factors were associated with SUD. The resilience factors familism, friendships, and family religiosity were not associated with any of the mental health outcomes. ACEs were associated with poorer mental health outcomes; however, none of the resilience factors exhibited interactions consistent with being protective for ACEs. Unexpectedly, higher family religiosity was associated with more perceived stress in the presence of higher ACEs. Conclusions and Relevance: The results of this study suggest that promoting positive relationships with adults during childhood may reduce later young adulthood stress and MDD/GAD. However, there is still a need to identify sociocultural childhood protective factors for ACEs. Caution should be taken in assuming what resilience factors are relevant for a given group, as higher family religiosity (one postulated resilience factor) was unexpectedly associated with a stronger, rather than a weaker, association between ACEs and perceived stress in young adulthood.

Decreased Self-reported Physical Fitness Following SARS-CoV-2 Infection and the Impact of Vaccine Boosters in a Cohort Study.

Background: The long-term effects of coronavirus disease 2019 (COVID-19) on physical fitness are unclear, and the impact of vaccination on that relationship is uncertain. Methods: We compared survey responses in a 1-year study of US military service members with (n = 1923) and without (n = 1591) a history of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We fit Poisson regression models to estimate the association between history of SARS-CoV-2 infection and fitness impairment, adjusting for time since infection, demographics, and baseline health. Results: The participants in this analysis were primarily young adults aged 18-39 years (75%), and 71.5% were male. Participants with a history of SARS-CoV-2 infection were more likely to report difficulty exercising (38.7% vs 18.4%; P < .01), difficulty performing daily activities (30.4% vs 12.7%; P < .01), and decreased fitness test (FT) scores (42.7% vs 26.2%; P < .01) than those without a history of infection. SARS-CoV-2-infected participants were at higher risk of these outcomes after adjusting for other factors (unvaccinated: exercising: adjusted risk ratio [aRR], 3.99; 95% CI, 3.36-4.73; activities: aRR, 5.02; 95% CI, 4.09-6.16; FT affected: aRR, 2.55; 95% CI, 2.19-2.98). Among SARS-CoV-2-positive participants, full vaccination before infection was associated with a lower risk of post-COVID-19 fitness impairment (fully vaccinated: exercise: aRR, 0.81; 95% CI, 0.70-0.95; activities: aRR, 0.76; 95% CI, 0.64-0.91; FT: aRR, 0.87; 95% CI, 0.76-1.00; boosted: exercise: aRR, 0.62; 95% CI, 0.51-0.74; activities: aRR, 0.52; 95% CI, 0.41-0.65; FT: aRR, 0.59; 95% CI, 0.49-0.70). Conclusions: In this study of generally young, healthy military service members, SARS-CoV-2 infection was associated with lower self-reported fitness and exercise capacity; vaccination and boosting were associated with lower risk of self-reported fitness loss.

Circadian preference and physical and cognitive performance in adolescence: A scoping review.

Adolescence is a crucial period of development which coincides with changes in circadian rhythmicity. This may augment the impact of circadian preference on performance in this group. We aimed to scope the literature available on chronotypes and their effect on physical and mental aspects of performance in adolescents. Studies were identified by systematically searching bibliographical databases and grey literature. The Morningness-Eveningness Questionnaire was the most frequently reported tool for circadian preference assessment. Academic achievement was the most prevailing outcome, with evidence suggesting that morning type adolescents tend to outperform evening types, yet the results vary depending on multiple factors. Performance in tests of intelligence and executive functions was generally better at optimal times of the day (synchrony effect). Physical performance was examined in 8 studies, with very heterogeneous outcomes. Although the associations between circadian preference and performance in adolescents are evident in some areas, there are many factors that may be involved in the relationship and require further investigation. This review highlights the assessment of physical performance in relation to chronotypes, the multidimensional assessment of circadian preference, and the need for longitudinal studies as priorities for further research.Protocol: OSF Registration - Public registration, DOI: 10.17605/OSF.IO/UCA3Z.

Time measurement in insect photoperiodism: external and internal coincidence.

The identity and nature of the photoperiodic photoreceptors are now quite well known, as is the nature of the endocrine regulation of the resulting diapauses. The central problem of time measurement-how the photoperiodic clock differentiates long from short days-however, is still obscure, known only from whole-animal experiments and abstract models, although it is clearly a function of the insect circadian system. This review describes some of these experiments in terms of oscillator entrainment and two widely applicable photoperiodic clock models, external and internal coincidence, mainly using data from experiments on flesh flies (Sarcophaga spp) and the parasitic wasp, Nasonia vitripennis.

Undiagnosing St Joan: She Does Not Need a Medical or Psychiatric Diagnosis.

ABSTRACT: This article traces the history of Joan of Arc through her brief life that includes leading an army in defense of France at the age of 17 and ending with her death at the stake at the age of 19. In her activities, St Joan reported that she was guided by voices and visions in which she communicated with venerated spiritual figures such as St Michael and St Margaret. Questions have arisen about the nature of these experiences, and various medical and psychiatric diagnoses have been offered by contemporary experts. In our effort to evaluate the diagnostic proposals, we have examined the incidence of voices and visions in the Middle Ages, and we have followed that with a review of nonpathologic voice-hearing in our own era. We then move on to an analysis of some proposed medical and psychiatric diagnoses, all of which we find unconvincing. With this background, we argue that St Joan does not warrant a medical or psychiatric diagnosis. Such a conclusion, however, leaves us with another issue, that of Joan's achievements. How do we understand an adolescent being able to lead an army? Addressing this question proves more difficult than deciding whether St Joan warrants a diagnosis. In addition to her achievements in the war against Britain, Joan of Arc stands out as both the most documented person in Western civilization up until her era, and as the only person who has been both condemned and canonized by the Catholic Church.

In vitro activity of rhinacanthin analogues against drug resistant Plasmodium falciparum isolates from Northeast Thailand.

BACKGROUND: New anti-malarial drugs are needed urgently to address the increasing challenges of drug-resistant falciparum malaria. Two rhinacanthin analogues containing a naphthoquinone moiety resembling atovaquone showed promising in-vitro activity against a P. falciparum laboratory reference strain (K1). The anti-malarial activity of these 2 compounds was further evaluated for P. falciparum field isolates from an area of multi-drug resistance in Northeast Thailand. METHODS: Using a pLDH enzyme-linked immunosorbent assay, four P. falciparum isolates from Northeast Thailand in 2018 were tested for in vitro sensitivity to the two synthetic rhinacanthin analogues 1 and 2 as well as established anti-malarials. Mutations in the P. falciparum cytochrome b gene, a marker for atovaquone (ATQ) resistance, were genotyped in all four field isolates as well as 100 other clinical isolates from the same area using PCR-artificial Restriction Fragment Length Polymorphisms. Pfkelch13 mutations, a marker for artemisinin (ART) resistance, were also examined in all isolates. RESULTS: The 50% inhibitory concentrations (IC50) of P. falciparum field isolates for rhinacanthin analogue 1 was 321.9-791.1 nM (median = 403.1 nM). Parasites were more sensitive to analogue 2: IC50 48.6-63.3 nM (median = 52.2 nM). Similar results were obtained against P. falciparum reference laboratory strains 3D7 and W2. The ART-resistant IPC-5202 laboratory strain was more sensitive to these compounds with a median IC50 45.9 and 3.3 nM for rhinacanthin analogues 1 and 2, respectively. The ATQ-resistant C2B laboratory strain showed high-grade resistance towards both compounds (IC50 > 15,000 nM), and there was a strong positive correlation between the IC50 values for these compounds and ATQ (r = 0.83-0.97, P < 0.001). There were no P. falciparum cytochrome b mutations observed in the field isolates, indicating that P. falciparum isolates from this area remained ATQ-sensitive. Pfkelch13 mutations and the ring-stage survival assay confirmed that most isolates were resistant to ART. CONCLUSIONS: Two rhinacanthin analogues showed parasiticidal activity against multi-drug resistant P. falciparum isolates, although less potent than ATQ. Rhinacanthin analogue 2 was more potent than analogue 1, and can be a lead compound for further optimization as an anti-malarial in areas with multidrug resistance.

Development, religious affiliation, and social context: Substance use disorders in Puerto Rican transitional age youth.

Introduction: Transitional age youth (i. e., ages 16-24; TAY) use higher levels of substances than any age group in the United States. Understanding what factors increase substance use during TAY could suggest novel targets for prevention/intervention. Studies suggest that religious affiliation is inversely associated with substance use disorders (SUDs). However, the association of religious affiliation and SUD, including the role of gender and social context, has not been studied in TAY of Puerto Rican ethnicity. Methods: Using data from N = 2,004 TAY of Puerto Rican ethnicity across two social contexts-Puerto Rico (PR) and the South Bronx, NY (SBx)-we tested the association of religious identity (Catholic, Non-Catholic Christian, Other/Mixed, and no religious affiliation, or "None"), and four SUD outcomes (alcohol use disorder, tobacco use disorder, illicit SUD, and any SUD). Logistic regression models were used to examine the association between religious identity and SUDs, then we tested for interaction by social context and gender. Result: Half the sample identified as female; 30, 44, and 25% were 15-20, 21-24, and 25-29 years of age, respectively; 28% of the sample received public assistance. There was a statistically significant difference between sites for public assistance (22 and 33% in SBx/PR, respectively; p < 0.001); 29% of the sample endorsed None (38 and 21% in SBx/PR, respectively.) Compared to None, identifying as Catholic was associated with reduced risk of illicit SUD (OR = 0.51, p = 0.02), and identifying as Non-Catholic Christian with reduced risk for any SUD (OR = 0.68, p = 0.04). Additionally, in PR but not SBx, being Catholic or Non-Catholic Christian was protective for illicit SUD when compared to None (OR = 0.13 and 0.34, respectively). We found no evidence of an interaction between religious affiliation and gender. Discussion: The percentage of PR TAY who endorse no affiliation is higher than the general PR population, reflective of increasing religious non-affiliation among TAY across cultures. Critically, TAY with no religious affiliation are twice as likely as Catholics to have illicit SUD, and 1.5 times as likely as Non-Catholic Christians to have any SUD. Endorsing no affiliation is more adverse for illicit SUD in PR than the SBx, underscoring the importance of social context.

A machine learning approach identifies distinct early-symptom cluster phenotypes which correlate with hospitalization, failure to return to activities, and prolonged COVID-19 symptoms.

BACKGROUND: Accurate COVID-19 prognosis is a critical aspect of acute and long-term clinical management. We identified discrete clusters of early stage-symptoms which may delineate groups with distinct disease severity phenotypes, including risk of developing long-term symptoms and associated inflammatory profiles. METHODS: 1,273 SARS-CoV-2 positive U.S. Military Health System beneficiaries with quantitative symptom scores (FLU-PRO Plus) were included in this analysis. We employed machine-learning approaches to identify symptom clusters and compared risk of hospitalization, long-term symptoms, as well as peak CRP and IL-6 concentrations. RESULTS: We identified three distinct clusters of participants based on their FLU-PRO Plus symptoms: cluster 1 ("Nasal cluster") is highly correlated with reporting runny/stuffy nose and sneezing, cluster 2 ("Sensory cluster") is highly correlated with loss of smell or taste, and cluster 3 ("Respiratory/Systemic cluster") is highly correlated with the respiratory (cough, trouble breathing, among others) and systemic (body aches, chills, among others) domain symptoms. Participants in the Respiratory/Systemic cluster were twice as likely as those in the Nasal cluster to have been hospitalized, and 1.5 times as likely to report that they had not returned-to-activities, which remained significant after controlling for confounding covariates (P < 0.01). Respiratory/Systemic and Sensory clusters were more likely to have symptoms at six-months post-symptom-onset (P = 0.03). We observed higher peak CRP and IL-6 in the Respiratory/Systemic cluster (P < 0.01). CONCLUSIONS: We identified early symptom profiles potentially associated with hospitalization, return-to-activities, long-term symptoms, and inflammatory profiles. These findings may assist in patient prognosis, including prediction of long COVID risk.

Persistent COVID-19 Symptoms at 6 Months After Onset and the Role of Vaccination Before or After SARS-CoV-2 Infection.

Importance: Understanding the factors associated with post-COVID conditions is important for prevention. Objective: To identify characteristics associated with persistent post-COVID-19 symptoms and to describe post-COVID-19 medical encounters. Design, Setting, and Participants: This cohort study used data from the Epidemiology, Immunology, and Clinical Characteristics of Emerging Infectious Diseases With Pandemic Potential (EPICC) study implemented in the US military health system (MHS); MHS beneficiaries aged 18 years or older who tested positive for SARS-CoV-2 from February 28, 2020, through December 31, 2021, were analyzed, with 1-year follow-up. Exposures: SARS-CoV-2 infection. Main Outcomes and Measures: The outcomes analyzed included survey-reported symptoms through 6 months after SARS-CoV-2 infection and International Statistical Classification of Diseases and Related Health Problems, Tenth Revision diagnosis categories reported in medical records 6 months following SARS-CoV-2 infection vs 3 months before infection. Results: More than half of the 1832 participants in these analyses were aged 18 to 44 years (1226 [66.9%]; mean [SD] age, 40.5 [13.7] years), were male (1118 [61.0%]), were unvaccinated at the time of their infection (1413 [77.1%]), and had no comorbidities (1290 [70.4%]). A total of 728 participants (39.7%) had illness that lasted 28 days or longer (28-89 days: 364 [19.9%]; ≥90 days: 364 [19.9%]). Participants who were unvaccinated prior to infection (risk ratio [RR], 1.39; 95% CI, 1.04-1.85), reported moderate (RR, 1.80; 95% CI, 1.47-2.22) or severe (RR, 2.25; 95% CI, 1.80-2.81) initial illnesses, had more hospitalized days (RR per each day of hospitalization, 1.02; 95% CI, 1.00-1.03), and had a Charlson Comorbidity Index score of 5 or greater (RR, 1.55; 95% CI, 1.01-2.37) were more likely to report 28 or more days of symptoms. Among unvaccinated participants, postinfection vaccination was associated with a 41% lower risk of reporting symptoms at 6 months (RR, 0.59; 95% CI, 0.40-0.89). Participants had higher risk of pulmonary (RR, 2.00; 95% CI, 1.40-2.84), diabetes (RR, 1.46; 95% CI, 1.00-2.13), neurological (RR, 1.29; 95% CI, 1.02-1.64), and mental health-related medical encounters (RR, 1.28; 95% CI, 1.01-1.62) at 6 months after symptom onset than at baseline (before SARS-CoV-2 infection). Conclusions and Relevance: In this cohort study, more severe acute illness, a higher Charlson Comorbidity Index score, and being unvaccinated were associated with a higher risk of reporting COVID-19 symptoms lasting 28 days or more. Participants with COVID-19 were more likely to seek medical care for diabetes, pulmonary, neurological, and mental health-related illness for at least 6 months after onset compared with their pre-COVID baseline health care use patterns. These findings may inform the risk-benefit ratio of COVID-19 vaccination policy.

Persistence and Mobility (defined as organic­carbon partitioning) do not correlate to the detection of substances found in surface and groundwater: Criticism of the regulatory concept of Persistent and mobile substances.

The Chemical Strategy for Sustainability (CSS) includes actions to ensure the protection of drinking water resources from chemical pollution. To proactively identify potential pollutants, the German Environment Agency (UBA) proposed the Persistent and Mobile (PM) concept according to which Persistence (criteria of REACH Annex XIII) and Mobility (log Koc < 4) would be proxies for a substance's degradation potential and transport velocity, two processes believed to drive the potential for contamination of surface and groundwater as drinking water sources. Two studies identified hundreds of PM substances while three subsequent studies have selected some of these substances for monitoring in surface, ground- and/or drinking water to support the concept. In the present work, the Persistence of the aforementioned substances was reassessed based on all experimental data publicly available. Depending on the exact study examined, it was found that 15 % to 40 % of the substances were erroneously concluded as P. The reinterpretation of the data indicates that a PM substance does not have a higher likelihood to be detected in surface or groundwater than a non-PM substance. In addition, the PM properties do not have any influence on the level of contamination. Twenty-six to 75 % of the substances selected because they were identified as PM were not found in surface or ground water despite being selected for their high emission pattern. Regulations based primarily on the PM concept, like the CLP and possibly REACH and UN-GHS, are unlikely to appropriately identify substances of concern for drinking water sources. It is more likely that chemical presence in surface and groundwater is driven by emission patterns or local factors. The development of specific exposure models would better contribute to the protection of drinking water resources and consumers.

Antigenic cartography of well-characterized human sera shows SARS-CoV-2 neutralization differences based on infection and vaccination history.

The rapid emergence of SARS-CoV-2 variants challenges vaccination strategies. Here, we collected 201 serum samples from persons with a single infection or multiple vaccine exposures, or both. We measured their neutralization titers against 15 natural variants and 7 variants with engineered spike mutations and analyzed antigenic diversity. Antigenic maps of primary infection sera showed that Omicron sublineages BA.2, BA.4/BA.5, and BA.2.12.1 are distinct from BA.1 and more similar to Beta/Gamma/Mu variants. Three mRNA COVID-19 vaccinations increased neutralization of BA.1 more than BA.4/BA.5 or BA.2.12.1. BA.1 post-vaccination infection elicited higher neutralization titers to all variants than three vaccinations alone, although with less neutralization to BA.2.12.1 and BA.4/BA.5. Those with BA.1 infection after two or three vaccinations had similar neutralization titer magnitude and antigenic recognition. Accounting for antigenic differences among variants when interpreting neutralization titers can aid the understanding of complex patterns in humoral immunity that informs the selection of future COVID-19 vaccine strains.

Efficacy of three anti-malarial regimens for uncomplicated Plasmodium falciparum malaria in Cambodia, 2009-2011: a randomized controlled trial and brief review.

BACKGROUND: Anti-malarial resistance remains an important public health challenge in Cambodia. The effectiveness of three therapies for uncomplicated falciparum malaria was evaluated in Oddar Meanchey province in Northern Cambodia from 2009 to 2011. METHODS: In this randomized, open-label, parallel group-controlled trial, 211 subjects at least 5 years old with uncomplicated falciparum malaria were treated with 3 days of directly observed therapy: 63 received artesunate-mefloquine (AS/MQ), 77 received dihydroartemisinin-piperaquine (DHA/PPQ), and 71 received atovaquone-proguanil (ATQ/PG). The subjects were followed for 42 days or until recurrent parasitaemia. Genotyping of msp1, msp2, and glurp among individual parasite isolates distinguished recrudescence from reinfection. Pfmdr1 copy number was measured by real-time PCR and half-maximal parasite inhibitory concentrations (IC50) were measured in vitro by 48-h isotopic hypoxanthine incorporation assay. RESULTS: The per-protocol PCR-adjusted efficacy (95% confidence interval) at 42 days was 80.6% (70.8-90.5%) for AS/MQ, 97.2% (93.3-100%) for DHA/PPQ, and 92.9% (86.1-99.6%) for ATQ/PG. On day 3, 57.9% remained parasitaemic in the AS/MQ and DHA/PPQ arms. At baseline, 46.9% had microscopic Plasmodium falciparum gametocytaemia. Both recurrences in the DHA/PPQ arm lost Pfmdr1 copy number amplification at recrudescence. All four recurrences in the ATQ/PG arm were wild-type for cytochrome bc1. One subject withdrew from the ATQ/PG arm due to drug allergy. CONCLUSIONS: This study was conducted at the epicentre of substantial multi-drug resistance that emerged soon thereafter. Occurring early in the national transition from AS/MQ to DHA/PPQ, both DHA/PPQ and ATQ/PG had acceptable efficacy against uncomplicated falciparum malaria. However, efficacy of AS/MQ was only 80% with apparent mefloquine resistance based on elevated Pfmdr1 copy number and IC50. By 2009, there was already significant evidence of artemisinin resistance not previously reported at the Northern Cambodia-Thai border. This study suggests the basis for early development of significant DHA/PPQ failures within 3 years of introduction. Artemisinin resistance likely occurred on the Northern border concurrently with that reported along the Western border in Pailin. Trial registration This legacy trial was conducted prior to International Committee of Medical Journal Editors' requirements for preregistration on ClinicalTrials.gov. The full protocol has been provided.

Hazard assessment of chemical constituents in biocide formulations used in offshore oil and gas operations.

Biocides used in offshore oil and gas operations could be present in water discharges, and thus identifying such chemicals and their hazard could help address concerns regarding non-target organisms. Aquatic toxicity data, queried from different sources and augmented with predictive models, were used to develop species sensitivity distributions and their corresponding 5th percentile hazard concentrations (HC5s). Curated data, including over 1000 empirical records for 137 species, indicated no evidence of bias when comparing sensitivity between marine and freshwater species, even when predicted data were used. HC5s facilitated estimation of an acute-to-chronic ratio (ACR = 10), appropriate for most chemicals and useful in filling data gaps. Comparison of chronic-HC5s with the default approach for deriving predicted no effect concentrations showed that the latter systematically overstates aquatic hazard. The present approach shows promise of using acute-to-chronic HC5 ratios for defining assessment factors for different chemical classes, instead of the use of generic assessment factors.

What works to reduce sedentary behavior in the office, and could these intervention components transfer to the home working environment?: A rapid review and transferability appraisal.

Background: Working patterns have changed dramatically due to COVID-19, with many workers now spending at least a portion of their working week at home. The office environment was already associated with high levels of sedentary behavior, and there is emerging evidence that working at home further elevates these levels. The aim of this rapid review (PROSPERO CRD42021278539) was to build on existing evidence to identify what works to reduce sedentary behavior in an office environment, and consider whether these could be transferable to support those working at home. Methods: The results of a systematic search of databases CENTRAL, MEDLINE, Embase, PsycInfo, CINHAL, and SportDiscus from 10 August 2017 to 6 September 2021 were added to the references included in a 2018 Cochrane review of office based sedentary interventions. These references were screened and controlled peer-reviewed English language studies demonstrating a beneficial direction of effect for office-based interventions on sedentary behavior outcomes in healthy adults were included. For each study, two of five authors screened the title and abstract, the full-texts, undertook data extraction, and assessed risk of bias on the included studies. Informed by the Behavior Change Wheel, the most commonly used intervention functions and behavior change techniques were identified from the extracted data. Finally, a sample of common intervention strategies were evaluated by the researchers and stakeholders for potential transferability to the working at home environment. Results: Twenty-two studies including 29 interventions showing a beneficial direction of effect on sedentary outcomes were included. The most commonly used intervention functions were training (n = 21), environmental restructuring (n = 21), education (n = 15), and enablement (n = 15). Within these the commonly used behavior change techniques were instructions on how to perform the behavior (n = 21), adding objects to the environment (n = 20), and restructuring the physical environment (n = 19). Those strategies with the most promise for transferring to the home environment included education materials, use of role models, incentives, and prompts. Conclusions: This review has characterized interventions that show a beneficial direction of effect to reduce office sedentary behavior, and identified promising strategies to support workers in the home environment as the world adapts to a new working landscape.Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021278539, identifier CRD42021278539.

Parental perspectives on attention-deficit/hyperactivity disorder treatments for children.

This study investigated parental perspectives and experiences on the evaluation and treatment process associated with attention-deficit/hyperactivity disorder (ADHD). Five hundred sixty-eight parents of youth 2-28 years-old (M = 9.37; SD = 4.11) diagnosed with ADHD responded to a 14-item online survey about their child's diagnosis and treatment. Parents reported that they had tried an average of 4.49 interventions (SD = 2.63). Parents further shared factors in treatment selection, most helpful parenting strategies, and preferences for types of treatments and treatment targets. A majority of parents reported incorporating many non-traditional strategies (e.g., exercise, healthy eating, outdoor activities) with goals of improving their child's coping skills, study habits, and anger management. The findings show that treatment choices were often selected based on trust in the provider, research support, and the child's preference. Given parental preferences for non-traditional strategies, treatment development efforts should consider these strategies as a component of a broader multimodal treatment approach to ADHD.