Detection of pediatric upper extremity motor activity and deficits with accelerometry

Importance: Affordable, quantitative methods to screen children for developmental delays are needed. Motor milestones can be an indicator of developmental delay and may be used to track developmental progress. Accelerometry offers a way to gather real-world information about pediatric motor behavior. Objective: To develop a referent cohort of pediatric accelerometry from bilateral upper extremities (UEs) and determine whether movement can accurately distinguish those with and without motor deficits. Design, Setting, and Participants: Children aged 0 to 17 years participated in a prospective cohort from December 8, 2014, to December 29, 2017. Children were recruited from Ranken Jordan Pediatric Bridge Hospital, Maryland Heights, Missouri, and Washington University School of Medicine in St Louis, St Louis, Missouri. Typically developing children were included as a referent cohort if they had no history of motor or neurological deficit; consecutive sampling and matching ensured equal representation of sex and age. Children with diagnosed asymmetric motor deficits were included in the motor impaired cohort. Exposures: Bilateral UE motor activity was measured using wrist-worn accelerometers for a total of 100 hours in 25-hour increments. Main Outcomes and Measures: To characterize bilateral UE motor activity in a referent cohort for the purpose of detecting irregularities in the future, total activity and the use ratio between UEs were used to describe typically developing children. Asymmetric impairment was classified using the mono-arm use index (MAUI) and bilateral-arm use index (BAUI) to quantify the acceleration of unilateral movements. Results: A total of 216 children enrolled, and 185 children were included in analysis. Of these, 156 were typically developing, with mean (SD) age 9.1 (5.1) years and 81 boys (52.0%). There were 29 children in the motor impaired cohort, with mean (SD) age 7.4 (4.4) years and 16 boys (55.2%). The combined MAUI and BAUI (mean [SD], 0.86 [0.005] and use ratio (mean [SD], 0.90 [0.008]) had similar F1 values. The area under the curve was also similar between the combined MAUI and BAUI (mean [SD], 0.98 [0.004]) and the use ratio (mean [SD], 0.98 [0.004]). Conclusions and Relevance: Bilateral UE movement as measured with accelerometry may provide a meaningful metric of real-world motor behavior across childhood. Screening in early childhood remains a challenge; MAUI may provide an effective method for clinicians to measure and visualize real-world motor behavior in children at risk for asymmetrical deficits

Effects of Age, Sex, and Neuropsychological Performance on Financial Decision-Making

The capacity to make sound financial decisions across the lifespan is critical for interpersonal, occupational, and psychological health and success. In the present study, we explored how healthy younger and older adults make a series of increasingly complex financial decisions. One-hundred sixteen healthy older adults, aged 56–90 years, and 102 college undergraduates, completed the Financial Decision-Making Questionnaire, which requires selecting and justifying financial choices across four hypothetical scenarios and answering questions pertaining to financial knowledge. Results indicated that Older participants significantly outperformed Younger participants on a multiple-choice test of acquired financial knowledge. However, after controlling for such pre-existing knowledge, several age effects were observed. For example, Older participants were more likely to make immediate investment decisions, whereas Younger participants exhibited a preference for delaying decision-making pending additional information. Older participants also rated themselves as more concerned with avoiding monetary loss (i.e., a prevention orientation), whereas Younger participants reported greater interest in financial gain (i.e., a promotion orientation). In terms of sex differences, Older Males were more likely to pay credit card bills and utilize savings accounts than were Older Females. Multiple positive correlations were observed between Older participants’ financial decision-making ability and performance on neuropsychological measures of non-verbal intellect and executive functioning. Lastly, the ability to justify one’s financial decisions declined with age, among the Older participants. Several of the aforementioned results parallel findings from the medical decision-making literature, suggesting that older adults make decisions in a manner that conserves diminishing cognitive resources

A translation and preliminary validation of the Dutch Wound-QoL questionnaire

Background: Chronic wounds have a major impact on patients' health-related quality of life (HRQoL). Therefore, measuring HRQoL is an indispensable part of the treatment of patients with chronic wounds. The aim of this study was to translate and validate the Wound-QoL, a wound-specific HRQoL questionnaire, in a Dutch population. Methods: The Wound-QoL was translated into Dutch according to the international standards. Patients with chronic wounds were asked to complete questionnaires at baseline (T0) and after six weeks (T1), including Wound-QoL, EQ-5D-3L (a generic questionnaire to measure HRQoL) and a visual analogue scale (VAS) measuring wound pain. If patients were not able to complete the questionnaire by themselves, it was read out to them by a nurse. Further data were obtained from medical records. Results: Of the 120 patients included, 64 (53.3%) completed the questionnaire by themselves. To 55 patients (45.8%), the questionnaire was read out. The internal consistency of the Wound-QoL global score was high at both time points (T0: Cronbach's α = 0.89, T1: Cronbach's α = 0.92). The item selectivity for global score ranged from r = 0.25 to r = 0.77 at T0 and from r = 0.40 to r = 0.79 at T1. Overall, the self-completion and read-out subgroups showed similar internal consistency and item selectivity scores. With regard to convergent validity, significant correlations were found between Wound-QoL and EQ-5D-3L (T0: r = - 0.45, p < 0.001, T1: r = - 0.50, p < 0.001) as well as between Wound-QoL and pain VAS (T0: r = 0.23, p = 0.012, T1: r = 0.37, p = 0.001) at both time points. Responsiveness analyses showed significant correlations between changes in Wound-QoL and changes in EQ-5D-3L (r = - 0.37, p < 0.001), pain VAS (r = 0.24, p = 0.044) and wound size (r = 0.24, p = 0.013). The self-completion and read-out subgroups showed differences in convergent validity and responsiveness. Conclusions: The results indicate that the Dutch version of the Wound-QoL has positive psychometric properties. However, more research is needed to further explore the differences between self-completed and read-out questionnaires

Simulations suggest a constrictive force is required for Gram-negative bacterial cell division

To divide, Gram-negative bacterial cells must remodel cell wall at the division site. It remains debated, however, whether this cell wall remodeling alone can drive membrane constriction, or if a constrictive force from the tubulin homolog FtsZ is required. Previously, we constructed software (REMODELER 1) to simulate cell wall remodeling during growth. Here, we expanded this software to explore cell wall division (REMODELER 2). We found that simply organizing cell wall synthesis complexes at the midcell is not sufficient to cause invagination, even with the implementation of a make-before-break mechanism, in which new hoops of cell wall are made inside the existing hoops before bonds are cleaved. Division can occur, however, when a constrictive force brings the midcell into a compressed state before new hoops of relaxed cell wall are incorporated between existing hoops. Adding a make-before-break mechanism drives division with a smaller constrictive force sufficient to bring the midcell into a relaxed, but not necessarily compressed, state

Understanding Wales: Nationalism and Culture

In the spring of 2013 ten students from the University of North Carolina Wilmington participated in a study abroad program in Wales attending Swansea University for the semester. As a group, we began examining Welsh culture and identity. Living abroad provided many opportunities to collect data and make observations about Welsh life. Our initial observations pointed to a tension that seemed to exist between Welsh and English cultures. We found this tension noteworthy and decided to examine it more closely through an exploratory research project examining Welsh political and economic history, Welsh culture and Welsh nationalism through participant observation, field trips and face-to-face interviews

Risk Factors for Appendiceal Cancer After Appendectomy

BackgroundAppendiceal cancer (AC) is a rare malignancy usually diagnosed incidentally after appendectomy. Risk factors for AC are poorly understood. We sought to provide a descriptive analysis for patients with AC discovered after appendectomy for acute appendicitis (AA).MethodsThe 2016-2017 American College of Surgeons-National Surgical Quality Improvement Program Procedure-Targeted Appendectomy database was queried for adult patients who underwent appendectomy for image-suspected AA. Patients with pathology consistent with AA were compared to patients found to have AC. A multivariable logistic regression model was used for analysis.ResultsFrom 21&nbsp;058 patients, 203 (1.0%) were found to have AC on pathology. Compared to patients with AA, patients with AC were older (median, 48 vs. 40&nbsp;years old, P &lt; .001). The AA group had a similar rate of perforated appendix compared to the AC group (16.3% vs. 13.4% P = .32). After adjusting for covariates, associated risk factors for AC were: age ≥65&nbsp;years old (odds ratio (OR) 2.25, 1.5-3.38, P &lt; .001), absence of leukocytosis (OR 1.58, 1.16-2.17, P = .004), and operative time ≥1&nbsp;hour (OR 1.57, 1.14-2.16, P = .006). Gender, race, and history of smoking were not independent associated risk factors for AC.ConclusionThe incidence of AC after appendectomy for suspected AA is approximately 1% in a large national analysis. These factors may be used to help identify patients at higher risk for AC after appendectomy

Randomised pharmacokinetic trial of rifabutin with lopinavir/ritonavir-antiretroviral therapy in patients with HIV-associated tuberculosis in Vietnam.

BACKGROUND: Rifampicin and protease inhibitors are difficult to use concomitantly in patients with HIV-associated tuberculosis because of drug-drug interactions. Rifabutin has been proposed as an alternative rifamycin, but there is concern that the current recommended dose is suboptimal. The principal aim of this study was to compare bioavailability of two doses of rifabutin (150 mg three times per week and 150 mg daily) in patients with HIV-associated tuberculosis who initiated lopinavir/ritonavir-based antiretroviral therapy in Vietnam. Concentrations of lopinavir/ritonavir were also measured. METHODS: This was a randomized, open-label, multi-dose, two-arm, cross-over trial, conducted in Vietnamese adults with HIV-associated tuberculosis in Ho Chi Minh City (Clinical trial registry number NCT00651066). Rifabutin pharmacokinetics were evaluated before and after the introduction of lopinavir/ritonavir -based antiretroviral therapy using patient randomization lists. Serial rifabutin and 25-O-desacetyl rifabutin concentrations were measured during a dose interval after 2 weeks of rifabutin 300 mg daily, after 3 weeks of rifabutin 150 mg daily with lopinavir/ritonavir and after 3 weeks of rifabutin 150 mg three times per week with lopinavir/ritonavir. RESULTS: Sixteen and seventeen patients were respectively randomized to the two arms, and pharmacokinetic analysis carried out in 12 and 13 respectively. Rifabutin 150 mg daily with lopinavir/ritonavir was associated with a 32% mean increase in rifabutin average steady state concentration compared with rifabutin 300 mg alone. In contrast, the rifabutin average steady state concentration decreased by 44% when rifabutin was given at 150 mg three times per week with lopinavir/ritonavir. With both dosing regimens, 2 - 5 fold increases of the 25-O-desacetyl- rifabutin metabolite were observed when rifabutin was given with lopinavir/ritonavir compared with rifabutin alone. The different doses of rifabutin had no significant effect on lopinavir/ritonavir plasma concentrations. CONCLUSIONS: Based on these findings, rifabutin 150 mg daily may be preferred when co-administered with lopinavir/ritonavir in patients with HIV-associated tuberculosis. TRIAL REGISTRATION: ClinicalTrials.gov NCT00651066

Stress-induced phase separation of ERES components into Sec bodies precedes ER exit inhibition in mammalian cells

Phase separation of components of ER exit sites (ERES) into membraneless compartments, the Sec bodies, occurs in Drosophila cells upon exposure to specific cellular stressors, namely, salt stress and amino acid starvation, and their formation is linked to the early secretory pathway inhibition. Here, we show Sec bodies also form in secretory mammalian cells upon the same stress. These reversible and membraneless structures are positive for ERES components, including both Sec16A and Sec16B isoforms and COPII subunits. We find that Sec16A, but not Sec16B, is a driver for Sec body formation, and that the coalescence of ERES components into Sec bodies occurs by fusion. Finally, we show that the stress-induced coalescence of ERES components into Sec bodies precedes ER exit inhibition, leading to their progressive depletion from ERES that become non-functional. Stress relief causes an immediate dissolution of Sec bodies and the concomitant restoration of ER exit. We propose that the dynamic conversion between ERES and Sec body assembly, driven by Sec16A, regulates protein exit from the ER during stress and upon stress relief in mammalian cells, thus providing a conserved pro-survival mechanism in response to stress