Freshwater diatom persistence on clothing II: Further analysis of species assemblage dynamics over investigative timescales

Diatoms are a useful form of environmental trace evidence, yielding a circumstantial link between persons and scenes of forensic interest. A developing empirical research base has sought to understand those factors affecting the transfer and persistence of freshwater diatoms on clothing and footwear surfaces. Although an initial study has demonstrated that diatoms can persist on clothing following weeks of wear, no previous research has explored the temporal dynamics of a persistent species assemblage over timescales pertinent to forensic investigations. This study therefore aimed to determine if: (1) valve morphology (size and shape) influences diatom persistence, (2) the relative abundance of taxa within an assemblage affects retention, and (3) a persistent diatom assemblage retrieved from clothing after one month can reliably be compared to the site of initial transfer. To build on previous research findings which highlighted the impact of substrate and environmental seasonality on diatom transfer and persistence, here, nine clothing materials were tested in spring before a seasonal comparison in the winter. Fabric swatches were immersed in a freshwater river, worn attached to clothing, and subsamples retrieved at regular intervals (hours, days, weeks) up to one month post-immersion. Diatoms were extracted using a H2O2 technique and analysed via microscopy. The results indicated that smaller diatoms (< 10 µm) are retained in significantly greater abundance, with no statistically significant difference between centric and pennate diatom loss over time. Although a persistent species assemblage was relatively stable over the one month of wear, significant differences were identified between clothing substrate in the spring and between the seasonal samples. The most abundant environmental taxa were consistently identified in the forensic samples, with greater variability attributed to the retention of relatively less common species. The findings suggest that, despite a loss in the abundance and species-richness of diatoms retrieved from clothing over time, a persistent assemblage may provide a useful circumstantial link to the site of initial transfer. The complex relationships between clothing type, environmental seasonality, and time since wear on retention, emphasise the need for diatom trace evidence to be carefully interpreted within an exclusionary framework, and the significance of any casework findings to be determined with reference to empirical evidence bases

Freshwater diatom persistence on clothing I: A quantitative assessment of trace evidence dynamics over time

Freshwater diatoms offer valuable circumstantial forensic indicators, with a growing empirical research base aiming to identify and understand some of the spatial and temporal factors affecting their validity as trace evidence. Previous studies demonstrated that recipient surface characteristics, environmental variability, and individual species traits influence the initial transfer of freshwater diatoms to clothing. However, no previous research has sought to consider the impact of these and other variables on the persistence of transferred diatoms over investigative timescales. Therefore, this study aimed to identify and explore diatom retention dynamics on clothing following wear over time (hours to weeks). A series of experiments were designed to examine the impact of clothing material, seasonality, and time since wear (persistence interval) on the total number and species-richness of diatoms recovered and their relative retention (%) over time. Nine clothing swatches were immersed in a freshwater environment and then worn for one month in the spring. Subsamples were retrieved at regular intervals (e.g. 30 mins, 1 h, 8 h, 24 h) up to one month, diatoms were extracted using a H2O2 method, and examined microscopically. Three clothing materials were subject to the same experiment in the winter to generate a seasonal comparison. The results broadly identified three stages of diatom persistence on clothing - rapid initial loss, variable intermediate decay, and sustained long-term presence. Clothing material significantly impacted the number of diatoms recovered and retention dynamics over time, with complex interactions identified with seasonality. Although fewer diatoms were recovered in the winter, overall retention trends were consistent at the different times of year. The findings demonstrate that diatoms can be recovered from clothing, even weeks or months after an initial transfer, yielding a useful environmental trace indicator for forensic reconstructions over investigative timescales. The impact of clothing material and seasonality on persistence identified cotton, acrylic, and viscose clothing as the most reliable temporal repository of diatom trace evidence, with a more abundant forensic assemblage available for forensic comparisons in the spring

Intrinsic function of the peptidylarginine deiminase PADI4 is dispensable for normal haematopoiesis.

Peptidylarginine deiminases (PADIs) are strongly associated with the development of autoimmunity, neurodegeneration and cancer but their physiological roles are ill-defined. The nuclear deiminase PADI4 regulates pluripotency in the mammalian pre-implantation embryo but its function in tissue development is unknown. PADI4 is primarily expressed in the bone marrow, as part of a self-renewal-associated gene signature. It has been shown to regulate the proliferation of multipotent haematopoietic progenitors and proposed to impact on the differentiation of haematopoietic stem cells (HSCs), suggesting that it controls haematopoietic development or regeneration. Using conditional in vivo models of steady state and acute Padi4 ablation, we examined the role of PADI4 in the development and function of the haematopoietic system. We found that PADI4 loss does not significantly affect HSC self-renewal or differentiation potential upon injury or serial transplantation, nor does it lead to HSC exhaustion or premature ageing. Thus PADI4 is dispensable for cell-autonomous HSC maintenance, differentiation and haematopoietic regeneration. This work represents the first study of PADI4 in tissue development and indicates that pharmacological PADI4 inhibition may be tolerated without adverse effects

Allele-specific NKX2-5 binding underlies multiple genetic associations with human electrocardiographic traits.

The cardiac transcription factor (TF) gene NKX2-5 has been associated with electrocardiographic (EKG) traits through genome-wide association studies (GWASs), but the extent to which differential binding of NKX2-5 at common regulatory variants contributes to these traits has not yet been studied. We analyzed transcriptomic and epigenomic data from induced pluripotent stem cell-derived cardiomyocytes from seven related individuals, and identified ~2,000 single-nucleotide variants associated with allele-specific effects (ASE-SNVs) on NKX2-5 binding. NKX2-5 ASE-SNVs were enriched for altered TF motifs, for heart-specific expression quantitative trait loci and for EKG GWAS signals. Using fine-mapping combined with epigenomic data from induced pluripotent stem cell-derived cardiomyocytes, we prioritized candidate causal variants for EKG traits, many of which were NKX2-5 ASE-SNVs. Experimentally characterizing two NKX2-5 ASE-SNVs (rs3807989 and rs590041) showed that they modulate the expression of target genes via differential protein binding in cardiac cells, indicating that they are functional variants underlying EKG GWAS signals. Our results show that differential NKX2-5 binding at numerous regulatory variants across the genome contributes to EKG phenotypes

High-efficiency Rosa26 knock-in vector construction for Cre-regulated overexpression and RNAi

Patients with heart failure (HF) and anaemia have greater functional impairment, worse symptoms, increased rates of hospital admission, and a higher risk of death, compared with non-anaemic HF patients. Whether correcting anaemia can improve outcomes is unknown. The Reduction of Events with Darbepoetin alfa in Heart Failure trial (RED-HF; Clinical Trials.gov NCT 003 58215) was designed to evaluate the effect of the long-acting erythropoietin-stimulating agent darbepoetin alfa on mortality and morbidity (and quality of life) in patients with HF and anaemia. Approximately 2600 patients with New York Heart Association class II-IV, an ejection fraction = 9.0 g/dL will be enrolled. Patients are randomized 1:1 to double-blind subcutaneous administration of darbepoetin alfa or placebo. Investigators are also blinded to Hb measurements and darbepoetin alfa is dosed to achieve an Hb concentration of 13.0 g/dL (but not exceeding 14.5 g/dL) with sham adjustments of the dose of placebo. The primary endpoint is the time to death from any cause or first hospital admission for worsening HF, whichever occurs first. The study will complete when similar to 1150 subjects experience a primary endpoint

The direction of postural threat alters balance control when standing at virtual elevation

This is the author accepted manuscript. The final version is available from Springer via the DOI in this recordAvailability of Data and Material: All data are available here: https://github.com/keithlohse/Gait_VR/tree/master/standing_balanceCode availability: All analysis code are available here: https://github.com/keithlohse/Gait_VR/tree/master/standing_balanceAnxiogenic settings lead to reduced postural sway while standing, but anxiety-related balance may be influenced by the location of postural threat in the environment. We predicted that the direction of threat would elicit a parallel controlled manifold relative to the standing surface, and an orthogonal uncontrolled manifold during standing. Altogether, 14 healthy participants (8 women, mean age = 27.5 yrs, SD = 8.2) wore a virtual reality (VR) headset and stood on a matched real-world walkway (2m x 40cm x 2cm) for 30s at ground level and simulated heights (elevated 15m) in two positions: (1) parallel to walkway, lateral threat; and (2) perpendicular to walkway, anteroposterior threat. Inertial sensors measured postural sway acceleration (e.g., 95% ellipse, root mean square (RMS) of acceleration), and a wrist-worn monitor measured heart rate coefficient of variation (HR CV). Fully factorial linear-mixed effect regressions (LMER) determined the effects of height and position. HR CV moderately increased from low to high height (p = 0.050, g = 0.397). The Height x Position interaction approached significance for sway area (95% ellipse; ß = -0.018, p = 0.062) and was significant for RMS (ß = -0.022, p = 0.007). Post-hoc analyses revealed that frontal plane sway accelerations and RMS increased from low to high elevation in parallel standing, but decreased when facing the threat during perpendicular standing. Postural response to threat varies depending on the direction of threat, suggesting that the control strategies used during standing are sensitive to the direction of threat.National Institutes of Health (NIH

Freshwater diatom persistence on clothing I: A quantitative assessment of trace evidence dynamics over time.

Freshwater diatoms offer valuable circumstantial forensic indicators, with a growing empirical research base aiming to identify and understand some of the spatial and temporal factors affecting their validity as trace evidence. Previous studies demonstrated that recipient surface characteristics, environmental variability, and individual species traits influence the initial transfer of freshwater diatoms to clothing. However, no previous research has sought to consider the impact of these and other variables on the persistence of transferred diatoms over investigative timescales. Therefore, this study aimed to identify and explore diatom retention dynamics on clothing following wear over time (hours to weeks). A series of experiments were designed to examine the impact of clothing material, seasonality, and time since wear (persistence interval) on the total number and species-richness of diatoms recovered and their relative retention (%) over time. Nine clothing swatches were immersed in a freshwater environment and then worn for one month in the spring. Subsamples were retrieved at regular intervals (e.g. 30 mins, 1 h, 8 h, 24 h) up to one month, diatoms were extracted using a H2O2 method, and examined microscopically. Three clothing materials were subject to the same experiment in the winter to generate a seasonal comparison. The results broadly identified three stages of diatom persistence on clothing - rapid initial loss, variable intermediate decay, and sustained long-term presence. Clothing material significantly impacted the number of diatoms recovered and retention dynamics over time, with complex interactions identified with seasonality. Although fewer diatoms were recovered in the winter, overall retention trends were consistent at the different times of year. The findings demonstrate that diatoms can be recovered from clothing, even weeks or months after an initial transfer, yielding a useful environmental trace indicator for forensic reconstructions over investigative timescales. The impact of clothing material and seasonality on persistence identified cotton, acrylic, and viscose clothing as the most reliable temporal repository of diatom trace evidence, with a more abundant forensic assemblage available for forensic comparisons in the spring

How acceptable are antiretrovirals for the prevention of sexually transmitted HIV? A review of research on the acceptability of oral pre-exposure prophylaxis and treatment as prevention

Recent research has demonstrated how antiretrovirals (ARVs) could be effective in the prevention of sexually transmitted HIV. We review research on the acceptability of oral pre-exposure prophylaxis (PrEP) and treatment as prevention (TasP) for HIV prevention amongst potential users. We consider with whom, where and in what context this research has been conducted, how acceptability has been approached, and what research gaps remain. Findings from 33 studies show a lack of TasP research, PrEP studies which have focused largely on men who have sex with men (MSM) in a US context, and varied measures of acceptability. In order to identify when, where and for whom PrEP and TasP would be most appropriate and effective, research is needed in five areas: acceptability of TasP to people living with HIV; motivation for PrEP use and adherence; current perceptions and management of risk; the impact of broader social and structural factors; and consistent definition and operationalisation of acceptability which moves beyond adherence

The stroke oxygen pilot study: a randomized control trial of the effects of routine oxygen supplementation early after acute stroke--effect on key outcomes at six months

Introduction: Post-stroke hypoxia is common, and may adversely affect outcome. We have recently shown that oxygen supplementation may improve early neurological recovery. Here, we report the six-month outcomes of this pilot study. Methods: Patients with a clinical diagnosis of acute stroke were randomized within 24 h of admission to oxygen supplementation at 2 or 3 L/min for 72 h or to control treatment (room air). Outcomes (see below) were assessed by postal questionnaire at 6 months. Analysis was by intention-to-treat, and statistical significance was set at p#0.05. Results: Out of 301 patients randomized two refused/withdrew consent and 289 (148 in the oxygen and 141 in the control group) were included in the analysis: males 44%, 51%; mean (SD) age 73 (12), 71 (12); median (IQR) National Institutes of Health Stroke Scale score 6 (3, 10), 5 (3, 10) for the two groups respectively. At six months 22 (15%) patients in the oxygen group and 20 (14%) in the control group had died; mean survival in both groups was 162 days (p= 0.99). Median (IQR) scores for the primary outcome, the modified Rankin Scale, were 3 (1, 5) and 3 (1, 4) for the oxygen and control groups respectively. The covariate-adjusted odds ratio was 1.04 (95% CI 0.67, 1.60), indicating that the odds of a lower (i.e. better) score were non-significantly higher in the oxygen group (p= 0.86). The mean differences in the ability to perform basic (Barthel Index) and extended activities of daily living (NEADL), and quality of life (EuroQol) were also non-significant. Conclusions: None of the key outcomes differed at 6 months between the groups. Although not statistically significant and generally of small magnitude, the effects were predominantly in favour of the oxygen group; a larger trial, powered to show differences in longer-term functional outcomes, is now on-going. Trial Registration: Controlled-Trials.com ISRCTN12362720; Eudract.ema.europa.eu 2004-001866-4

Alcohol-induced retrograde facilitation renders witnesses of crime less suggestible to misinformation

RATIONALE: Research has shown that alcohol can have both detrimental and facilitating effects on memory: intoxication can lead to poor memory for information encoded after alcohol consumption (anterograde amnesia) and may improve memory for information encoded before consumption (retrograde facilitation). This study examined whether alcohol consumed after witnessing a crime can render individuals less vulnerable to misleading post-event information (misinformation). METHOD: Participants watched a simulated crime video. Thereafter, one third of participants expected and received alcohol (alcohol group), one third did not expect but received alcohol (reverse placebo), and one third did not expect nor receive alcohol (control). After alcohol consumption, participants were exposed to misinformation embedded in a written narrative about the crime. The following day, participants completed a cued-recall questionnaire about the event. RESULTS: Control participants were more likely to report misinformation compared to the alcohol and reverse placebo group. CONCLUSION: The findings suggest that we may oversimplify the effect alcohol has on suggestibility and that sometimes alcohol can have beneficial effects on eyewitness memory by protecting against misleading post-event information