Tolerability and safety of the intake of bovine milk oligosaccharides extracted from cheese whey in healthy human adults.

Mechanistic research suggests a unique evolutionary relationship between complex milk oligosaccharides and cognate bifidobacteria enriched in breast-fed infants. Bovine milk oligosaccharides (BMO) were recently identified as structurally and functionally similar to human milk oligosaccharides. The present single-blind three-way crossover study is the first to determine the safety and tolerability of BMO consumption by healthy human participants (n 12) and its effects on faecal microbiota and microbial metabolism. Participants consumed each supplement (placebo-control; low- and high-BMO doses) for eleven consecutive days, followed by a 2-week washout period prior to initiating the next supplement arm. Low and high BMO doses were consumed as 25 and 35 % of each individual's daily fibre intake, respectively. Safety and tolerability were measured using standardised questionnaires on gut and stomach discomfort and stool consistency. Faecal extracts were profiled for bacterial populations by next-generation sequencing (NGS) and bifidobacteria presence was confirmed using quantitative PCR. Urine was analysed for changes in microbial metabolism using nuclear magnetic resonance spectroscopy (1H-NMR). Consumption of both the low and high BMO doses was well tolerated and did not change stool consistency from baseline. Multivariate analysis of the NGS results demonstrated no change in faecal microbiota phyla among the placebo-control and BMO supplement groups. In conclusion, BMO supplementation was well tolerated in healthy adults and has the potential to shift faecal microbiota toward beneficial strains as part of a synbiotic treatment with probiotic cultures that selectively metabolise oligosaccharides

Commentary on Guyll et al. (2023): Misuse of Statistical Method Results in Highly Biased Interpretation of Forensic Evidence

Since the National Academy of Sciences released their report outlining paths for improving reliability, standards, and policies in the forensic sciences NAS (2009), there has been heightened interest in evaluating and improving the scientific validity within forensic science disciplines. Guyll et al. (2023) seek to evaluate the validity of forensic cartridge-case comparisons. However, they make a serious statistical error that leads to highly inflated claims about the probability that a cartridge case from a crime scene was fired from a reference gun, typically a gun found in the possession of a defendant. It is urgent to address this error since these claims, which are generally biased against defendants, are being presented by the prosecution in an ongoing homicide case where the defendant faces the possibility of a lengthy prison sentence (DC Superior Court, 2023)

Potential for allocative harm in an environmental justice data tool

Neighborhood-level screening algorithms are increasingly being deployed to inform policy decisions. We evaluate one such algorithm, CalEnviroScreen - designed to promote environmental justice and used to guide hundreds of millions of dollars in public funding annually - assessing its potential for allocative harm. We observe the model to be sensitive to subjective model decisions, with 16% of tracts potentially changing designation, as well as financially consequential, estimating the effect of its positive designations as a 104% (62-145%) increase in funding, equivalent to \$2.08 billion (\$1.56-2.41 billion) over four years. We also observe allocative tradeoffs and susceptibility to manipulation, raising ethical concerns. We recommend incorporating sensitivity analyses to mitigate allocative harm and accountability mechanisms to prevent misuse

A pneumatic power harvesting ankle-foot orthosis to prevent foot-drop

<p>Abstract</p> <p>Background</p> <p>A self-contained, self-controlled, pneumatic power harvesting ankle-foot orthosis (PhAFO) to manage foot-drop was developed and tested. Foot-drop is due to a disruption of the motor control pathway and may occur in numerous pathologies such as stroke, spinal cord injury, multiple sclerosis, and cerebral palsy. The objectives for the prototype PhAFO are to provide toe clearance during swing, permit free ankle motion during stance, and harvest the needed power with an underfoot bellow pump pressurized during the stance phase of walking.</p> <p>Methods</p> <p>The PhAFO was constructed from a two-part (tibia and foot) carbon composite structure with an articulating ankle joint. Ankle motion control was accomplished through a cam-follower locking mechanism actuated via a pneumatic circuit connected to the bellow pump and embedded in the foam sole. Biomechanical performance of the prototype orthosis was assessed during multiple trials of treadmill walking of an able-bodied control subject (n = 1). Motion capture and pressure measurements were used to investigate the effect of the PhAFO on lower limb joint behavior and the capacity of the bellow pump to repeatedly generate the required pneumatic pressure for toe clearance.</p> <p>Results</p> <p>Toe clearance during swing was successfully achieved during all trials; average clearance 44 ± 5 mm. Free ankle motion was observed during stance and plantarflexion was blocked during swing. In addition, the bellow component repeatedly generated an average of 169 kPa per step of pressure during ten minutes of walking.</p> <p>Conclusion</p> <p>This study demonstrated that fluid power could be harvested with a pneumatic circuit built into an AFO, and used to operate an actuated cam-lock mechanism that controls ankle-foot motion at specific periods of the gait cycle.</p

Pathologic gene network rewiring implicates PPP1R3A as a central regulator in pressure overload heart failure

Heart failure is a leading cause of mortality, yet our understanding of the genetic interactions underlying this disease remains incomplete. Here, we harvest 1352 healthy and failing human hearts directly from transplant center operating rooms, and obtain genome-wide genotyping and gene expression measurements for a subset of 313. We build failing and non-failing cardiac regulatory gene networks, revealing important regulators and cardiac expression quantitative trait loci (eQTLs). PPP1R3A emerges as a regulator whose network connectivity changes significantly between health and disease. RNA sequencing after PPP1R3A knockdown validates network-based predictions, and highlights metabolic pathway regulation associated with increased cardiomyocyte size and perturbed respiratory metabolism. Mice lacking PPP1R3A are protected against pressure-overload heart failure. We present a global gene interaction map of the human heart failure transition, identify previously unreported cardiac eQTLs, and demonstrate the discovery potential of disease-specific networks through the description of PPP1R3A as a central regulator in heart failure

Improving Long-Term Adherence to Monitoring/Treatment in Underserved Asian Americans with Chronic Hepatitis B (CHB) through a Multicomponent Culturally Tailored Intervention: A Randomized Controlled Trial

Background: Although Asian Americans make up 6% of the U.S. population, they account for 58% of Americans with chronic hepatitis B (CHB). Yet, adherence to monitoring and antiviral treatment guidelines among Asian American CHB patients remains suboptimal. Methods: The purpose of this study was to evaluate the efficacy of a multicomponent intervention on adherence to CHB monitoring among Asian Americans with CHB. The intervention components included virtual patient education, patient navigation, and mobile health reminders delivered by bilingual community health educators. Chi-square test and t -test were used to compare demographic characteristics and two CHB measures: CHB clinical follow-up and CHB laboratory monitoring by the time of the 12-month follow-up assessment. A generalized linear mixed-effects model (GLMM) was fitted to assess the effectiveness of the intervention. Results: The study sample consisted of 358 Chinese and Vietnamese Americans living with CHB, including 181 in the intervention group and 177 in the control group. The intervention group had a significantly higher rate of CHB clinical follow- up (86.2%) and CHB laboratory monitoring (79.0%) than did the control group (54.2% and 45.2%, respectively). Results of the GLMM showed significant intervention effects on CHB clinical follow-up (odds ratio = 7.35, 95% confidence interval = 4.06–13.33) and CHB laboratory monitoring (odds ratio = 6.60, 95% confidence interval = 3.77–11.56) at the 12-month follow-up assessment. Conclusion: The multicomponent intervention was effective in improving adherence to CHB monitoring among Asian Americans. Additional implementation research is needed to better understand and apply effective interventions to other underserved populations

Factors Associated with Hepatitis B Medication Adherence and Persistence among Underserved Chinese and Vietnamese Americans

Background: Hepatitis B virus (HBV) infection disproportionately affects Asian Amer- icans in the United States, while this population faces low adherence to HBV treatment. Using the information–motivation–behavioral skills model (IMB), the study aims to examine medication adherence and persistence among Chinese and Vietnamese people with HBV. Methodology: Study participants were recruited between March 2019 and March 2020 and were enrolled through multiple recruitment approaches in the Greater Philadelphia Area and New York City. The study is an assess- ment of the baseline data on medication adherence, HBV-related knowledge, motivation of HBV med- ication treatment, self-efficacy about HBV medication treatment, and socioeconomic status. Results: Among 165 participants, 77.6% were Chinese and 22.4% were Vietnamese Americans. HBV-related knowledge/information, motivation, and self-efficacy were all positively associated with having medium/high medication adherence. Multilevel mixed-effects generalized linear regression revealed that living more than 10 years in the U.S. (OR = 4.24; p = 0.028) and greater information–knowledge about HBV (OR = 1.46; p = 0.004) were statistically associated with higher odds of medium/high medication adherence. Moreover, greater HBV-related knowledge/information ( OR = 1.49; p = 0.023) and greater motivation towards HBV treatment adherence (OR = 1.10; p = 0.036) were both associated with a higher likelihood of medication persistence. Conclusion: Our findings provided significant im- plications in designing behavioral interventions focused on self-efficacy, information, and motivation to promote better medication adherence among Asian Americans living with HBV

The ALMA Interferometric Pipeline Heuristics

We describe the calibration and imaging heuristics developed and deployed in the ALMA interferometric data processing pipeline, as of ALMA Cycle 9. The pipeline software framework is written in Python, with each data reduction stage layered on top of tasks and toolkit functions provided by the Common Astronomy Software Applications package. This framework supports a variety of tasks for observatory operations, including science data quality assurance, observing mode commissioning, and user reprocessing. It supports ALMA and VLA interferometric data along with ALMA and NRO45m single dish data, via different stages and heuristics. In addition to producing calibration tables, calibrated measurement sets, and cleaned images, the pipeline creates a WebLog which serves as the primary interface for verifying the data quality assurance by the observatory and for examining the contents of the data by the user. Following the adoption of the pipeline by ALMA Operations in 2014, the heuristics have been refined through annual development cycles, culminating in a new pipeline release aligned with the start of each ALMA Cycle of observations. Initial development focused on basic calibration and flagging heuristics (Cycles 2-3), followed by imaging heuristics (Cycles 4-5), refinement of the flagging and imaging heuristics with parallel processing (Cycles 6-7), addition of the moment difference analysis to improve continuum channel identification (2020 release), addition of a spectral renormalization stage (Cycle 8), and improvement in low SNR calibration heuristics (Cycle 9). In the two most recent Cycles, 97% of ALMA datasets were calibrated and imaged with the pipeline, ensuring long-term automated reproducibility. We conclude with a brief description of plans for future additions, including self-calibration, multi-configuration imaging, and calibration and imaging of full polarization data.Comment: accepted for publication by Publications of the Astronomical Society of the Pacific, 65 pages, 20 figures, 10 tables, 2 appendice

Predictors of mortality in HIV-1 infected children on antiretroviral therapy in Kenya: a prospective cohort

<p>Abstract</p> <p>Background</p> <p>Among children, early mortality following highly active antiretroviral therapy (HAART) remains high. It is important to define correlates of mortality in order to improve outcome.</p> <p>Methods</p> <p>HIV-1-infected children aged 18 months-12 years were followed up at Kenyatta National Hospital, Nairobi after initiating NNRTI-based HAART. Cofactors for mortality were determined using multivariate Cox regression models.</p> <p>Results</p> <p>Between August 2004 and November 2008, 149 children were initiated on HAART of whom 135 were followed for a total of 238 child-years (median 21 months) after HAART initiation. Baseline median CD4% was 6.8% and median HIV-1-RNA was 5.98-log₁₀copies/ml. Twenty children (13.4%) died at a median of 35 days post-HAART initiation. Mortality during the entire follow-up period was 8.4 deaths per 100 child-years (46 deaths/100 child-years in first 4 months and 1.0 deaths/100 child-years after 4 months post-HAART initiation). On univariate Cox regression, baseline hemoglobin (Hb) <9 g/dl, weight-for-height z-score (WHZ) < -2, and WHO clinical stage 4 were associated with increased risk of death (Hb <9 g/dl HR 3.00 [95% C.I. 1.21-7.39], p = 0.02, WHZ < -2 HR 3.41 [95% C.I. 1.28-9.08], p = 0.01, and WHO clinical stage 4, HR 3.08 [1.17-8.12], p = 0.02). On multivariate analysis Hb < 9 g/dl remained predictive of mortality after controlling for age, baseline CD4%, WHO clinical stage and weight-for-height z-score (HR 2.95 (95% C.I. 1.04-8.35) p = 0.04).</p> <p>Conclusion</p> <p>High early mortality was observed in this cohort of Kenyan children receiving HAART, and low baseline hemoglobin was an independent risk factor for death.</p