Multidecadal increase in plastic particles in coastal ocean sediments.

We analyzed coastal sediments of the Santa Barbara Basin, California, for historical changes in microplastic deposition using a box core that spanned 1834-2009. The sediment was visually sorted for plastic, and a subset was confirmed as plastic polymers via FTIR (Fourier transform infrared) spectroscopy. After correcting for contamination introduced during sample processing, we found an exponential increase in plastic deposition from 1945 to 2009 with a doubling time of 15 years. This increase correlated closely with worldwide plastic production and southern California coastal population increases over the same period. Increased plastic loading in sediments has unknown consequences for deposit-feeding benthic organisms. This increase in plastic deposition in the post-World War II years can be used as a geological proxy for the Great Acceleration of the Anthropocene in the sedimentary record

Functional connectivity in the first year of life in infants at-risk for autism: a preliminary near-infrared spectroscopy study

Background: Autism spectrum disorder (ASD) has been called a “developmental disconnection syndrome,” however the majority of the research examining connectivity in ASD has been conducted exclusively with older children and adults. Yet, prior ASD research suggests that perturbations in neurodevelopmental trajectories begin as early as the first year of life. Prospective longitudinal studies of infants at risk for ASD may provide a window into the emergence of these aberrant patterns of connectivity. The current study employed functional connectivity near-infrared spectroscopy (NIRS) in order to examine the development of intra- and inter-hemispheric functional connectivity in high- and low-risk infants across the first year of life. Methods: NIRS data were collected from 27 infants at high risk for autism (HRA) and 37 low-risk comparison (LRC) infants who contributed a total of 116 data sets at 3-, 6-, 9-, and 12-months. At each time point, HRA and LRC groups were matched on age, sex, head circumference, and Mullen Scales of Early Learning scores. Regions of interest (ROI) were selected from anterior and posterior locations of each hemisphere. The average time course for each ROI was calculated and correlations for each ROI pair were computed. Differences in functional connectivity were examined in a cross-sectional manner. Results: At 3-months, HRA infants showed increased overall functional connectivity compared to LRC infants. This was the result of increased connectivity for intra- and inter-hemispheric ROI pairs. No significant differences were found between HRA and LRC infants at 6- and 9-months. However, by 12-months, HRA infants showed decreased connectivity relative to LRC infants. Conclusions: Our preliminary results suggest that atypical functional connectivity may exist within the first year of life in HRA infants, providing support to the growing body of evidence that aberrant patterns of connectivity may be a potential endophenotype for ASD

Supporting Cells Remove and Replace Sensory Receptor Hair Cells in a Balance Organ of Adult Mice

Vestibular hair cells in the inner ear encode head movements and mediate the sense of balance. These cells undergo cell death and replacement (turnover) throughout life in non-mammalian vertebrates. However, there is no definitive evidence that this process occurs in mammals. We used fate-mapping and other methods to demonstrate that utricular type II vestibular hair cells undergo turnover in adult mice under normal conditions. We found that supporting cells phagocytose both type I and II hair cells. Plp1-CreER(T2)-expressing supporting cells replace type II hair cells. Type I hair cells are not restored by Plp1-CreER(T2)-expressing supporting cells or by Atoh1-CreER(TM)-expressing type II hair cells. Destruction of hair cells causes supporting cells to generate 6 times as many type II hair cells compared to normal conditions. These findings expand our understanding of sensorineural plasticity in adult vestibular organs and further elucidate the roles that supporting cells serve during homeostasis and after injury

The pitfalls of electronic health orders: Development of an enhanced institutional protocol after a preventable patient death

BACKGROUND: Continuous bladder irrigation (CBI) is a long-standing treatment used in the setting of gross hematuria and other acute bladder issues. Its use has traditionally been reserved for patients under direct urologic care, but with the constraints of modern large-hospital healthcare, many patients have CBI administered by providers unfamiliar with its use and potential complications. FINDINGS: There were 136 CBI orders placed in 2013 by non-urologic providers. The biggest hazard found in our analysis was the requirement for entering a rate of irrigation administration. Nurses with no experience with CBI viewed this order as an indication to administer via an infusion pump, which can easily exceed the mechanical integrity of the bladder and increase the risk of bladder perforation. Our panel also found that due to lack of experience by nurses and non-urologic providers, that signs and symptoms of CBI dysfunction were not common knowledge. Also we found that non-urologic providers were unfamiliar with administration and dosing of medications for CBI patients to help with the intrinsic discomfort with CBI administration. CONCLUSIONS: In our revised order set we found that removing the requirement for an infusion rate, along with placing warnings in the CPOE, helped staff better understand this possible complication. We created a best practice alert in our CPOE to strongly recommend the urology service be consulted. Communication text boxes were added to the order set to help staff be aware of the signs and symptoms of CBI dysfunction, along with a guide for trouble shooting

Myeloid tissue factor does not modulate lung inflammation or permeability during experimental acute lung injury

Tissue factor (TF) is a critical mediator of direct acute lung injury (ALI) with global TF deficiency resulting in increased airspace inflammation, alveolar-capillary permeability, and alveolar hemorrhage after intra-tracheal lipopolysaccharide (LPS). In the lung, TF is expressed diffusely on the lung epithelium and intensely on cells of the myeloid lineage. We recently reported that TF on the lung epithelium, but not on myeloid cells, was the major source of TF during intra-tracheal LPS-induced ALI. Because of a growing body of literature demonstrating important pathophysiologic differences between ALI caused by different etiologies, we hypothesized that TF on myeloid cells may have distinct contributions to airspace inflammation and permeability between direct and indirect causes of ALI. To test this, we compared mice lacking TF on myeloid cells (TF∆mye, LysM.Cre+/−TFflox/flox) to littermate controls during direct (bacterial pneumonia, ventilator-induced ALI, bleomycin-induced ALI) and indirect ALI (systemic LPS, cecal ligation and puncture). ALI was quantified by weight loss, bronchoalveolar lavage (BAL) inflammatory cell number, cytokine concentration, protein concentration, and BAL procoagulant activity. There was no significant contribution of TF on myeloid cells in multiple models of experimental ALI, leading to the conclusion that TF in myeloid cells is not a major contributor to experimental ALI

A Systematic Study of the In Vitro Pharmacokinetics and Estimated Human In Vivo Clearance of Indole and Indazole-3-Carboxamide Synthetic Cannabinoid Receptor Agonists Detected on the Illicit Drug Market

In vitro pharmacokinetic studies were conducted on enantiomer pairs of twelve valinate or tert-leucinate indole and indazole-3-carboxamide synthetic cannabinoid receptor agonists (SCRAs) detected on the illicit drug market to investigate their physicochemical parameters and structure-metabolism relationships (SMRs). Experimentally derived Log D7.4 ranged from 2.81 (AB-FUBINACA) to 4.95 (MDMB-4en-PINACA) and all SCRAs tested were highly protein bound, ranging from 88.9 ± 0.49% ((R)-4F-MDMB-BINACA) to 99.5 ± 0.08% ((S)-MDMB-FUBINACA). Most tested SCRAs were cleared rapidly in vitro in pooled human liver microsomes (pHLM) and pooled cryopreserved human hepatocytes (pHHeps). Intrinsic clearance (CLint) ranged from 13.7 ± 4.06 ((R)-AB-FUBINACA) to 2944 ± 95.9 mL min−1 kg−1 ((S)-AMB-FUBINACA) in pHLM, and from 110 ± 34.5 ((S)-AB-FUBINACA) to 3216 ± 607 mL min−1 kg−1 ((S)-AMB-FUBINACA) in pHHeps. Predicted Human in vivo hepatic clearance (CLH) ranged from 0.34 ± 0.09 ((S)-AB-FUBINACA) to 17.79 ± 0.20 mL min−1 kg−1 ((S)-5F-AMB-PINACA) in pHLM and 1.39 ± 0.27 ((S)-MDMB-FUBINACA) to 18.25 ± 0.12 mL min−1 kg−1 ((S)-5F-AMB-PINACA) in pHHeps. Valinate and tert-leucinate indole and indazole-3-carboxamide SCRAs are often rapidly metabolised in vitro but are highly protein bound in vivo and therefore predicted in vivo CLH is much slower than CLint. This is likely to give rise to longer detection windows of these substances and their metabolites in urine, possibly as a result of accumulation of parent drug in lipid-rich tissues, with redistribution into the circulatory system and subsequent metabolism

X-ray micro-computed tomography of polymer electrolyte fuel cells: what is the representative elementary area?

With the growing use of X-ray computed tomography (X-ray CT) datasets for modelling of transport properties, comes the need to define the representative elementary volume (REV) if considering three dimensions or the representative elementary area (REA) if considering two dimensions. The resolution used for imaging must be suited to the features of interest in the sample and the region-of-interest must be sufficiently large to capture key information. Polymer electrolyte fuel cells have a hierarchical structure, with materials spanning multiple length scales. The work presented here examines the nature of the REA throughout a 25 cm2 membrane electrode assembly (MEA), focusing specifically on the micron length scale. Studies were carried out to investigate key structural (volume fraction, layer and penetration thickness, pore diameters) and transport (effective diffusivity) properties. Furthermore, the limiting current density of the nine regions was modelled. Stochastic heterogeneity throughout the sample results in local variations throughout. Finally, effects of resolution were probed by imaging using a range of optical magnifications (4× and 20×). The correlated and competing effects of voxel resolution and sampling size were found to cause difficulties where loss of clarity in the boundaries between phases occurs with larger imaging volumes.Jennifer Hack acknowledges a studentship from the EPSRC Centre for Doctoral Training in Advanced Characterisation of Materials (EP/LO15277/1) and the hydrogen and fuel cell research in the Electrochemical Innovation Lab (EIL) is supported through EPSRC projects (EP/M014371/1, EP/S018204/2, EP/R023581/1, EP/P009050/1, EP/L015749/1, EP/M009394/1, EP/M023508/1). Paul R. Shearing acknowledges funding from the Royal Academy of Engineering (CiET1718/59). Pablo A. García-Salaberri thanks the support from the STFC Early Career Award (ST/R006873/1) during his stay at the EIL

Projected effects of disruptions to human immunodeficiency virus (HIV) prevention services during the coronavirus disease 2019 pandemic among Black/African American men who have sex with men in an Ending the HIV Epidemic priority jurisdiction

BACKGROUND: Disruptions in access to in-person human immunodeficiency virus (HIV) preventive care during the coronavirus disease 2019 (COVID-19) pandemic may have a negative impact on our progress towards the Ending the HIV Epidemic goals in the United States. METHODS: We used an agent-based model to simulate HIV transmission among Black/African American men who have sex with men in Mississippi over 5 years to estimate how different reductions in access affected the number of undiagnosed HIV cases, new pre-exposure prophylaxis (PrEP) starts, and HIV incidence. RESULTS: We found that each additional 25% decrease in HIV testing and PrEP initiation was associated with decrease of 20% in the number of cases diagnosed and 23% in the number of new PrEP starts, leading to a 15% increase in HIV incidence from 2020 to 2022. CONCLUSIONS: Unmet need for HIV testing and PrEP prescriptions during the COVID-19 pandemic may temporarily increase HIV incidence in the years immediately after the disruption period