hiPSC-derived hepatocytes closely mimic the lipid profile of primary hepatocytes: A future personalised cell model for studying the lipid metabolism of the liver

Peer reviewe

Safety and efficacy of ABT-089 in pediatric attention-deficit/hyperactivity disorder: results from two randomized placebo-controlled clinical trials.

OBJECTIVE: To assess the safety and efficacy of ABT-089, a novel α(4)β(2) neuronal nicotinic receptor partial agonist, vs. placebo in children with attention-deficit/hyperactivity disorder (ADHD). METHOD: Two multicenter, randomized, double-blind, placebo-controlled, parallel-group studies of children 6 through 12 years of age were conducted. Study 1 (n = 274) assessed six treatment groups over 8 weeks: 4 once-daily (QD) ABT-089 doses (0.085-0.700 mg/kg), QD atomoxetine, and placebo. Study 2 (n = 119) assessed three treatment groups over 6 weeks: 2 QD ABT-089 doses (0.7 mg/kg, 1.4 mg/kg) and placebo. The primary efficacy variable was the investigator-administered Attention-Deficit/Hyperactivity Disorder Rating Scale-IV: Home Version (ADHD-RS-IV [HV]) Total Score. Safety was assessed by adverse event (AE) monitoring, laboratory tests, vital signs, physical examinations, and electrocardiogram measures. RESULTS: There was no statistically significant difference between ABT-089 and placebo in mean change from baseline to final evaluation of ADHD-RS-IV (HV) Total Score or other outcome measures at any dose in either study. In Study 1, atomoxetine showed statistically significant improvement for the primary and most secondary endpoints. ABT-089 was generally safe and well tolerated, with no statistically significant difference between any ABT-089 dose and placebo in the overall incidence of any specific AE, and no clinically significant changes in other safety measures. CONCLUSIONS: ABT-089 did not show efficacy on the primary efficacy variable, the ADHD-RS-IV (HV) Total Score, or other measures of ADHD symptomatology in children with ADHD, and had a safety profile similar to placebo. These results contrast with published reports of efficacy of nicotinic modulators in adults with ADHD

Lengths of stay for involuntarily held psychiatric patients in the ED are affected by both patient characteristics and medication use

BACKGROUND: Psychiatric patients experience longer treatment times (length of stay [LOS]) in the emergency department (ED) compared to nonpsychiatric patients. Although patients on involuntary mental health holds are relatively understudied, common wisdom would hold that times for these patients can only be affected by addressing systems issues because they are not free to leave. The objective of this study was to determine whether both selected ED and patient-specific factors were associated with longer LOS. We hypothesized that nonmodifiable factors (age, sex, agitation, presentation during evenings/nights, presentation during weekends, suicidal ideation) would prolong LOS but that potentially modifiable factors (such as use of medication) would reduce LOS. METHODS: A historical cohort of patients (January 1, 2009-August 16, 2010) placed on involuntary mental health holds was studied in 2 general EDs. A regression model was used to calculate the effects of modifiable and nonmodifiable factors on LOS. RESULTS: Six hundred forty patient visits met all inclusion/exclusion criteria. Longer LOSs were significantly associated with suicidal ideation, use of antipsychotics, and use of benzodiazepines, although agitation did not predict longer LOSs. Longer LOSs were also longer with presentation on the weekends. CONCLUSIONS: Lengths of stay for patients on involuntary mental health holds are associated with several factors outside the control of the typical ED clinician such as the ability to clear holds quickly due to day of week or placement of the hold for suicidal ideation. Lengths of stay are also increased by factors within the control of the typical ED clinician, such as administration of calming medication

Geoscience Education Perspectives on Integrated, Coordinated, Open, Networked (ICON) Science

Practitioners and researchers in geoscience education embrace collaboration applying ICON (Integrated, Coordinated, Open science, and Networked) principles and approaches ICON principles and approaches have been used to create and share large collections of educational resources, to move forward collective priorities, and to foster peer-learning among educators. These strategies can also support the advancement of coproduction between geoscientists and diverse communities. For this reason, many authors from the geoscience education community have co-created three commentaries on the use and future of ICON in geoscience education. We envision that sharing our expertise with ICON practice will be useful to other geoscience communities seeking to strengthen collaboration. Geoscience education brings substantial expertise in social science research and its application to building individual and collective capacity to address earth sustainability and equity issues at local to global scales The geoscience education community has expanded its own ICON capacity through access to and use of shared resources and research findings, enhancing data sharing and publication, and leadership development. We prioritize continued use of ICON principles to develop effective and inclusive communities that increase equity in geoscience education and beyond, support leadership and full participation of systemically non-dominant groups and enable global discussions and collaborations

Mortality Among Adults With Cancer Undergoing Chemotherapy or Immunotherapy and Infected With COVID-19

Importance: Large cohorts of patients with active cancers and COVID-19 infection are needed to provide evidence of the association of recent cancer treatment and cancer type with COVID-19 mortality. // Objective: To evaluate whether systemic anticancer treatments (SACTs), tumor subtypes, patient demographic characteristics (age and sex), and comorbidities are associated with COVID-19 mortality. // Design, Setting, and Participants: The UK Coronavirus Cancer Monitoring Project (UKCCMP) is a prospective cohort study conducted at 69 UK cancer hospitals among adult patients (≥18 years) with an active cancer and a clinical diagnosis of COVID-19. Patients registered from March 18 to August 1, 2020, were included in this analysis. // Exposures: SACT, tumor subtype, patient demographic characteristics (eg, age, sex, body mass index, race and ethnicity, smoking history), and comorbidities were investigated. // Main Outcomes and Measures: The primary end point was all-cause mortality within the primary hospitalization. // Results: Overall, 2515 of 2786 patients registered during the study period were included; 1464 (58%) were men; and the median (IQR) age was 72 (62-80) years. The mortality rate was 38% (966 patients). The data suggest an association between higher mortality in patients with hematological malignant neoplasms irrespective of recent SACT, particularly in those with acute leukemias or myelodysplastic syndrome (OR, 2.16; 95% CI, 1.30-3.60) and myeloma or plasmacytoma (OR, 1.53; 95% CI, 1.04-2.26). Lung cancer was also significantly associated with higher COVID-19–related mortality (OR, 1.58; 95% CI, 1.11-2.25). No association between higher mortality and receiving chemotherapy in the 4 weeks before COVID-19 diagnosis was observed after correcting for the crucial confounders of age, sex, and comorbidities. An association between lower mortality and receiving immunotherapy in the 4 weeks before COVID-19 diagnosis was observed (immunotherapy vs no cancer therapy: OR, 0.52; 95% CI, 0.31-0.86). // Conclusions and Relevance: The findings of this study of patients with active cancer suggest that recent SACT is not associated with inferior outcomes from COVID-19 infection. This has relevance for the care of patients with cancer requiring treatment, particularly in countries experiencing an increase in COVID-19 case numbers. Important differences in outcomes among patients with hematological and lung cancers were observed

COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study

Background: The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods: International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results: ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≤ 18 years: 69, 48, 23; 85%), older adults (≥ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P < 0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. Interpretation: This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men

A HCMV pp65 polypeptide promotes the expansion of CD4+ and CD8+ T cells across a wide range of HLA specificities

Human Cytomegalovirus (HCMV) can cause life threatening disease in infected hosts. Immunization with HLA-restricted immunodominant synthetic peptides and adoptive transfer of epitope specific T cells have been envisaged to generate or boost HCMV specific cellular immunity, thereby preventing HCMV infection or reactivation. However, induction or expansion of T cells effective against HCMV are limited by the need of utilizing peptides with defined HLA restrictions. We took advantage of a combination of seven predictive algorithms to identify immunogenic peptides of potential use in the prevention or treatment of HCMV infection or reactivation. Here we describe a pp65 derived peptide (pp65(340-355), RQYDPVAALFFFDIDL: RQY16-mer), characterized by peculiar features. First, RQY-16mer is able to stimulate HCMV pp65 specific responses in both CD4+ and CD8+ T cells, restricted by a wide range of HLA class I and class II determinants. Second, RQY-16mer is able to induce an unusually wide range of effector functions in CD4+ T cells, including proliferation, killing of autologous HCMV infected target cells and cytokine production. Third, and most importantly, the RQY-16mer is able to stimulate CD4+ and CD8+ T cell responses in pharmacologically immunosuppressed patients. These data suggest that a single reagent might qualify as synthetic immunogen for potentially large populations exposed to HCMV infection or reactivation