Developing a pragmatic consensus procedure supporting the ICH S1B(R1) weight of evidence carcinogenicity assessment.

The ICH S1B carcinogenicity global testing guideline has been recently revised with a novel addendum that describes a comprehensive integrated Weight of Evidence (WoE) approach to determine the need for a 2-year rat carcinogenicity study. In the present work, experts from different organizations have joined efforts to standardize as much as possible a procedural framework for the integration of evidence associated with the different ICH S1B(R1) WoE criteria. The framework uses a pragmatic consensus procedure for carcinogenicity hazard assessment to facilitate transparent, consistent, and documented decision-making and it discusses best-practices both for the organization of studies and presentation of data in a format suitable for regulatory review. First, it is acknowledged that the six WoE factors described in the addendum form an integrated network of evidence within a holistic assessment framework that is used synergistically to analyze and explain safety signals. Second, the proposed standardized procedure builds upon different considerations related to the primary sources of evidence, mechanistic analysis, alternative methodologies and novel investigative approaches, metabolites, and reliability of the data and other acquired information. Each of the six WoE factors is described highlighting how they can contribute evidence for the overall WoE assessment. A suggested reporting format to summarize the cross-integration of evidence from the different WoE factors is also presented. This work also notes that even if a 2-year rat study is ultimately required, creating a WoE assessment is valuable in understanding the specific factors and levels of human carcinogenic risk better than have been identified previously with the 2-year rat bioassay alone.

A brief note on substantial sub-daily arsenic variability in pumping drinking-water wells in New Hampshire.

Large variations in redox-related water parameters, like pH and dissolved oxygen (DO), have been documented in New Hampshire (United States) drinking-water wells over the course of a few hours under pumping conditions. These findings suggest that comparable sub-daily variability in dissolved concentrations of redox-reactive and toxic arsenic (As) also may occur, representing a potentially critical public-health data gap and a fundamental challenge for long-term As-trends monitoring. To test this hypothesis, discrete groundwater As samples were collected approximately hourly during one day in May and again in August 2019 from three New Hampshire drinking-water wells (2 public-supply, 1 private) under active pumping conditions. Collected samples were assessed by laboratory analysis (total As [AsTot], As(III), As(V)) and by field analysis (AsTot) using a novel integrated biosensor system. Laboratory analysis revealed sub-daily variability (range) in AsTot concentrations equivalent to 16 % - 36 % of that observed in the antecedent 3-year bimonthly trend monitoring. Thus, the results indicated that, along with previously demonstrated seasonality effects, the timing and duration of pumping are important considerations when assessing trends in drinking-water As exposures and concomitant risks. Results also illustrated the utility of the field sensor for monitoring and management of AsTot exposures in near-real-time.

'Setting the Benchmark' Part 2: Contextualising the Physical Demands of Teams in the FIFA World Cup Qatar 2022.

This study aimed to contextualise and benchmark the physical demands of teams in the FIFA World Cup Qatar 2022. With FIFA's official approval, all sixty-four games were analysed during the competition (n = 32 teams) using a multi-camera computerised tracking system. On average, teams during Qatar 2022 covered around 108.1 ± 3.6 km in total, with 9.0 ± 0.9 and 2.3 ± 0.3 km covered at the higher intensities (≥20.0 and ≥25.0 km · h-1), respectively. Compared to the FIFA World Cup Russia 2018, national teams in Qatar 2022 covered only 3% more total distance but 16-19% more distance at the higher intensities (P < 0.01; Effect Size [ES]: 0.9-2.0). When the data was adjusted based on the number of minutes played, tournament differences at the higher intensities were less pronounced (9-12%; P < 0.01; ES: 0.7-1.3). The United States, Canada, Saudi Arabia, Germany and IR Iran covered 19-34% more high-intensity distance than Argentina, Ecuador, Qatar, Poland and Costa Rica during the 2022 tournament (P < 0.01; ES: 3.2-3.5). Match-to-match variation of each team in Qatar 2022 revealed Ecuador and Uruguay were particularly consistent for the distances covered at higher intensities (Coefficient of Variation [CV]: 2-3%), whilst Japan demonstrated considerable variation (CV: 23-29%). Teams generally covered more total distance on a per-minute basis in the first versus the second half (P < 0.01; ES: 1.2), but no differences existed at higher intensities (P > 0.05; ES: 0.0-0.1). Correlations between the number of high-intensity runs and various phase of play events across all teams were strongest for defensive transitions and recoveries, in addition to progressions up the pitch and into the final third (r = 0.63-0.75; P < 0.01). The present findings provide valuable context into the contemporary team demands of international football. This information could be useful for practitioners to benchmark team performances and to potentially understand the myriad of factors impacting physical performances.

'Setting the Benchmark' Part 1: The Contextualised Physical Demands of Positional Roles in the FIFA World Cup Qatar 2022.

This study aimed to contextualise and benchmark the positional role demands during the FIFA World Cup Qatar 2022. With FIFA's official approval, all sixty-four games were analysed during the competition (n=722) using a multi-camera computerised tracking system. During a typical FIFA World Cup Qatar 2022 match, defensive and central midfielders covered 8-19% more total distance than other positional roles (P<0.01; Effect Size [ES]: 0.8-2.5). The distances covered at higher intensities (≥20 and ≥25 km · h-1) were 16-92% and 36-138% higher for wide midfielders and wide forwards compared to central defenders, defensive and central midfielders as well as centre forwards (P<0.01; ES: 0.7-2.2 and ES: 0.6-1.4). Defensive and central midfielders covered a greater proportion of their distance at higher intensities (≥20 and ≥25 km · h-1) out-of-possession (71-83%; P<0.01; ES: 1.4-3.0), whilst attacking midfielders, wide and centre forwards more in-possession (55-68%; P<0.01; ES: 1.6-3.3). Nine out of the top ten sprint speeds attained at the tournament were from wide positional roles (35.3-35.7 km · h-1). All positional roles demonstrated a second half reduction in total distance covered compared to the first half (P<0.01; ES: 0.8-1.3). A decline between halves for the distances covered at higher intensities (≥20 and ≥25 km · h-1) were more evident in attacking midfielders, wide defenders and midfielders than for other positional roles (P<0.01; ES: 0.3-0.7). Defensive midfielders and centre forwards were found to have the highest coefficient of variation (CV: 30.9-35.9% and 67.7-67.8%) for the distances covered at higher intensities (≥20 and ≥25 km · h-1) compared to other positional roles. The current findings provide valuable contextual information about the contemporary positional demands of international football. This could be useful in the development and prescription of specific training regimes for national teams.

Multiple lines of evidence point to pesticides as stressors affecting invertebrate communities in small streams in five United States regions.

Multistressor studies were performed in five regions of the United States to assess the role of pesticides as stressors affecting invertebrate communities in wadable streams. Pesticides and other chemical and physical stressors were measured in 75 to 99 streams per region for 4 weeks, after which invertebrate communities were surveyed (435 total sites). Pesticides were sampled weekly in filtered water, and once in bed sediment. The role of pesticides as a stressor to invertebrate communities was assessed by evaluating multiple lines of evidence: toxicity predictions based on measured pesticide concentrations, multivariate models and other statistical analyses, and previously published mesocosm experiments. Toxicity predictions using benchmarks and species sensitivity distributions and statistical correlations suggested that pesticides were present at high enough concentrations to adversely affect invertebrate communities at the regional scale. Two undirected techniques-boosted regression tree models and distance-based linear models-identified which pesticides were predictors of (respectively) invertebrate metrics and community composition. To put insecticides in context with known, influential covariates of invertebrate response, generalized additive models were used to identify which individual pesticide(s) were important predictors of invertebrate community condition in each region, after accounting for natural covariates. Four insecticides were identified as stressors to invertebrate communities at the regional scale: bifenthrin, chlordane, fipronil and its degradates, and imidacloprid. Fipronil was particularly important in the Southeast region, and imidacloprid, bifenthrin, and chlordane were important in multiple regions. For imidacloprid, bifenthrin, and fipronil, toxicity predictions were supported by mesocosm experiments that demonstrated adverse effects on naïve aquatic communities when dosed under controlled conditions. These multiple lines of evidence do not prove causality-which is challenging in the field under multistressor conditions-but they make a strong case for the role of insecticides as stressors adversely affecting invertebrate communities in streams within the five sampled regions.

Original SARS-CoV-2 monovalent and Omicron BA.4/BA.5 bivalent COVID-19 mRNA vaccines: phase 2/3 trial interim results.

This ongoing, open-label, phase 2/3 trial compared the safety and immunogenicity of the Omicron BA.4/BA.5-containing bivalent mRNA-1273.222 vaccine with the ancestral Wuhan-Hu-1 mRNA-1273 as booster doses. Two groups of adults who previously received mRNA-1273 as primary vaccination series and booster doses were enrolled in a sequential, nonrandomized manner and received single-second boosters of mRNA-1273 (n = 376) or bivalent mRNA-1273.222 (n = 511). Primary objectives were safety and the noninferiority or superiority of neutralizing antibody (nAb) responses against Omicron BA.4/BA.5 and ancestral SARS-CoV-2 with the D614G mutation (ancestral SARS-CoV-2 (D614G)), 28 days post boost. Superiority and noninferiority were based on prespecified success criteria (lower bounds of 95% CI > 1 and < 0.677, respectively) of the mRNA-1273.222:mRNA-1273 geometric mean ratios. Bivalent Omicron BA.4/BA.5-containing mRNA-1273.222 elicited superior nAb responses against BA.4/BA.5 versus mRNA-1273 and noninferior responses against ancestral SARS-CoV-2 (D614G) at day 29 post boost in participants without detectable prior SARS-CoV-2 infection. Day 29 seroresponses against Omicron BA.4/BA.5 were higher for mRNA-1273.222 than for mRNA-1273 and similar against ancestral SARS-CoV-2 (D614G), both meeting noninferiority criterion. The safety profile of mRNA-1273.222 was similar to that previously reported for mRNA-1273 with no new safety concerns identified. Continued monitoring of neutralization and real-world vaccine effectiveness are needed as additional divergent-virus variants emerge. ClinicalTrials.gov registration: NCT04927065.

Changes in chemical occurrence, concentration, and bioactivity in the Colorado River before and after replacement of the Moab, Utah wastewater treatment plant.

Long-term (2010-19) water-quality monitoring on the Colorado River downstream from Moab Utah indicated the persistent presence of Bioactive Chemicals (BC), such as pesticides and pharmaceuticals. This stream reach near Canyonlands National Park provides critical habitat for federally endangered species. The Moab wastewater treatment plant (WWTP) outfall discharges to the Colorado River and is the nearest potential point-source to this reach. The original WWTP was replaced in 2018. In 2016-19, a study was completed to determine if the new plant reduced BC input to the Colorado River at, and downstream from, the outfall. Water samples were collected before and after the plant replacement at sites upstream and downstream from the outfall. Samples were analyzed for as many as 243 pesticides, 109 pharmaceuticals, 20 hormones, 51 wastewater indicator chemicals, 20 metals, and 8 nutrients. BC concentrations, hazard quotients (HQs), and exposure activity ratios (EARs) were used to identify and prioritize contaminants for their potential to have adverse biological effects on the health of native and endangered wildlife. There were 22 BC with HQs >1, mostly metals and hormones; and 23 BC with EARs >0.1, mostly hormones and pharmaceuticals. Most high HQs or EARs were associated with samples collected at the WWTP outfall site prior to its replacement. Discharge from the new plant had reduced concentrations of nutrients, hormones, pharmaceuticals, and other BC. For example, all 16 of the hormones detected at the WWTP outfall site had maximum concentrations in samples collected prior to the WWTP replacement. The WWTP replacement had less effect on instream concentrations of metals and pesticides, BC whose sources are less directly tied to domestic wastewater. Study results indicate that improved WWTP technology can create substantial reductions in concentrations of non-regulated BC such as pharmaceuticals, in addition to regulated contaminants such as nutrients.

Per- and polyfluoroalkyl substances (PFAS) in United States tapwater: Comparison of underserved private-well and public-supply exposures and associated health implications.

Drinking-water quality is a rising concern in the United States (US), emphasizing the need to broadly assess exposures and potential health effects at the point-of-use. Drinking-water exposures to per- and poly-fluoroalkyl substances (PFAS) are a national concern, however, there is limited information on PFAS in residential tapwater at the point-of-use, especially from private-wells. We conducted a national reconnaissance to compare human PFAS exposures in unregulated private-well and regulated public-supply tapwater. Tapwater from 716 locations (269 private-wells; 447 public supply) across the US was collected during 2016-2021 including three locations where temporal sampling was conducted. Concentrations of PFAS were assessed by three laboratories and compared with land-use and potential-source metrics to explore drivers of contamination. The number of individual PFAS observed ranged from 1 to 9 (median: 2) with corresponding cumulative concentrations (sum of detected PFAS) ranging from 0.348 to 346 ng/L. Seventeen PFAS were observed at least once with PFBS, PFHxS and PFOA observed most frequently in approximately 15% of the samples. Across the US, PFAS profiles and estimated median cumulative concentrations were similar among private wells and public-supply tapwater. We estimate that at least one PFAS could be detected in about 45% of US drinking-water samples. These detection probabilities varied spatially with limited temporal variation in concentrations/numbers of PFAS detected. Benchmark screening approaches indicated potential human exposure risk was dominated by PFOA and PFOS, when detected. Potential source and land-use information was related to cumulative PFAS concentrations, and the number of PFAS detected; however, corresponding relations with specific PFAS were limited likely due to low detection frequencies and higher detection limits. Information generated supports the need for further assessments of cumulative health risks of PFAS as a class and in combination with other co-occurring contaminants, particularly in unmonitored private-wells where information is limited or not available.

Density declines, richness increases, and composition shifts in stream macroinvertebrates.

Documenting trends of stream macroinvertebrate biodiversity is challenging because biomonitoring often has limited spatial, temporal, and taxonomic scopes. We analyzed biodiversity and composition of assemblages of >500 genera, spanning 27 years, and 6131 stream sites across forested, grassland, urban, and agricultural land uses throughout the United States. In this dataset, macroinvertebrate density declined by 11% and richness increased by 12.2%, and insect density and richness declined by 23.3 and 6.8%, respectively, over 27 years. In addition, differences in richness and composition between urban and agricultural versus forested and grassland streams have increased over time. Urban and agricultural streams lost the few disturbance-sensitive taxa they once had and gained disturbance-tolerant taxa. These results suggest that current efforts to protect and restore streams are not sufficient to mitigate anthropogenic effects.

Contextualised high-intensity running profiles of elite football players with reference to general and specialised tactical roles.

The present study aimed to contextualise physical metrics with tactical actions according to general and specialised tactical roles. A total of 244 English Premier League players were analysed by coding player's physical-tactical actions via the fusion of tracking data and video. Data were analysed across 5 general (Central Defensive Players = CDP, Wide Defensive Players = WDP, Central Midfield Players = CMP, Wide Offensive Players = WOP, Central Offensive Players = COP) and 11 specialised positions (Centre Backs = CB, Full-Backs = FB, Wing-Backs = WB, Box-to-Box Midfielders = B2BM, Central Defensive Midfielders = CDM, Central Attacking Midfielders = CAM, Wide Midfielders = WM, Wide Forwards = WF, Centre Forwards = CF). COP covered more distance at high-intensity (> 19.8 km · h-1) when performing actions such as 'Break into Box', Run in Behind/Penetrate', and 'Close Down/Press' than other positions (ES: 0.6-5.2, P < 0.01). WOP covered more high-intensity 'Run with Ball' distance (ES: 0.7-1.7, P < 0.01) whereas WDP performed more 'Over/Underlap' distance than other positions (ES: 0.9-1.4, P < 0.01). CDP and WDP covered more high-intensity 'Covering' distances than other positions (ES: 0.4-2.4, P < 0.01). Nonetheless, data demonstrated that implementing specialised positional analysis relative to a generalised approach is more sensitive in measuring physical-tactical performances of players with the latter over or underestimating the match demands of the players compared to the former. A contextualised analysis may assist coaches and practitioners when designing position or even player-specific training drills since the data provides unique physical-tactical trends across specialised roles.

Juxtaposition of intensive agriculture, vulnerable aquifers, and mixed chemical/microbial exposures in private-well tapwater in northeast Iowa.

In the United States and globally, contaminant exposure in unregulated private-well point-of-use tapwater (TW) is a recognized public-health data gap and an obstacle to both risk-management and homeowner decision making. To help address the lack of data on broad contaminant exposures in private-well TW from hydrologically-vulnerable (alluvial, karst) aquifers in agriculturally-intensive landscapes, samples were collected in 2018-2019 from 47 northeast Iowa farms and analyzed for 35 inorganics, 437 unique organics, 5 in vitro bioassays, and 11 microbial assays. Twenty-six inorganics and 51 organics, dominated by pesticides and related transformation products (35 herbicide-, 5 insecticide-, and 2 fungicide-related), were observed in TW. Heterotrophic bacteria detections were near ubiquitous (94 % of the samples), with detection of total coliform bacteria in 28 % of the samples and growth on at least one putative-pathogen selective media across all TW samples. Health-based hazard index screening levels were exceeded frequently in private-well TW and attributed primarily to inorganics (nitrate, uranium). Results support incorporation of residential treatment systems to protect against contaminant exposure and the need for increased monitoring of rural private-well homes. Continued assessment of unmonitored and unregulated private-supply TW is needed to model contaminant exposures and human-health risks.

Contaminant Exposure and Transport from Three Potential Reuse Waters within a Single Watershed.

Global demand for safe and sustainable water supplies necessitates a better understanding of contaminant exposures in potential reuse waters. In this study, we compared exposures and load contributions to surface water from the discharge of three reuse waters (wastewater effluent, urban stormwater, and agricultural runoff). Results document substantial and varying organic-chemical contribution to surface water from effluent discharges (e.g., disinfection byproducts [DBP], prescription pharmaceuticals, industrial/household chemicals), urban stormwater (e.g., polycyclic aromatic hydrocarbons, pesticides, nonprescription pharmaceuticals), and agricultural runoff (e.g., pesticides). Excluding DBPs, episodic storm-event organic concentrations and loads from urban stormwater were comparable to and often exceeded those of daily wastewater-effluent discharges. We also assessed if wastewater-effluent irrigation to corn resulted in measurable effects on organic-chemical concentrations in rain-induced agricultural runoff and harvested feedstock. Overall, the target-organic load of 491 g from wastewater-effluent irrigation to the study corn field during the 2019 growing season did not produce substantial dissolved organic-contaminant contributions in subsequent rain-induced runoff events. Out of the 140 detected organics in source wastewater-effluent irrigation, only imidacloprid and estrone had concentrations that resulted in observable differences between rain-induced agricultural runoff from the effluent-irrigated and nonirrigated corn fields. Analyses of pharmaceuticals and per-/polyfluoroalkyl substances in at-harvest corn-plant samples detected two prescription antibiotics, norfloxacin and ciprofloxacin, at concentrations of 36 and 70 ng/g, respectively, in effluent-irrigated corn-plant samples; no contaminants were detected in noneffluent irrigated corn-plant samples.

Bottled water contaminant exposures and potential human effects.

BACKGROUND: Bottled water (BW) consumption in the United States and globally has increased amidst heightened concern about environmental contaminant exposures and health risks in drinking water supplies, despite a paucity of directly comparable, environmentally-relevant contaminant exposure data for BW. This study provides insight into exposures and cumulative risks to human health from inorganic/organic/microbial contaminants in BW. METHODS: BW from 30 total domestic US (23) and imported (7) sources, including purified tapwater (7) and spring water (23), were analyzed for 3 field parameters, 53 inorganics, 465 organics, 14 microbial metrics, and in vitro estrogen receptor (ER) bioactivity. Health-benchmark-weighted cumulative hazard indices and ratios of organic-contaminant in vitro exposure-activity cutoffs were assessed for detected regulated and unregulated inorganic and organic contaminants. RESULTS: 48 inorganics and 45 organics were detected in sampled BW. No enforceable chemical quality standards were exceeded, but several inorganic and organic contaminants with maximum contaminant level goal(s) (MCLG) of zero (no known safe level of exposure to vulnerable sub-populations) were detected. Among these, arsenic, lead, and uranium were detected in 67 %, 17 %, and 57 % of BW, respectively, almost exclusively in spring-sourced samples not treated by advanced filtration. Organic MCLG exceedances included frequent detections of disinfection byproducts (DBP) in tapwater-sourced BW and sporadic detections of DBP and volatile organic chemicals in BW sourced from tapwater and springs. Precautionary health-based screening levels were exceeded frequently and attributed primarily to DBP in tapwater-sourced BW and co-occurring inorganic and organic contaminants in spring-sourced BW. CONCLUSION: The results indicate that simultaneous exposures to multiple drinking-water contaminants of potential human-health concern are common in BW. Improved understandings of human exposures based on more environmentally realistic and directly comparable point-of-use exposure characterizations, like this BW study, are essential to public health because drinking water is a biological necessity and, consequently, a high-vulnerability vector for human contaminant exposures.

Transcranial direct current stimulation during a prolonged cognitive task: the effect on cognitive and shooting performances in professional female basketball players.

The negative effect of prolonged cognitive demands on psychomotor skills in athletes has been demonstrated. Transcranial direct current stimulation (tDCS) could be used to mitigate this effect. This study examined the effects of tDCS over the left dorsolateral prefrontal cortex (DLPFC) during a 30-min inhibitory Stroop task on cognitive and shooting performances of professional female basketball players. Following a randomised, double-blinded, sham-controlled, cross-over design, players were assigned to receive anodal tDCS (a-tDCS, 2 mA for 20 min) or sham-tDCS in two different sessions. Data from 8 players were retained for analysis. Response Time decreased significantly over time (p < 0.001; partial η2 = 0.44; no effect of condition, or condition vs. time interaction). No difference in mean accuracy and shooting performance was observed between tDCS conditions. The results suggest that a-tDCS exert no additional benefits in reducing the negative effects of prolonged cognitive demands on technical performance compared to sham (placebo).Practitioner summary: Prolonged cognitive demands can negatively affect the athletes' performance. We tested whether transcranial direct current stimulation (tDCS) over the left dorsolateral prefrontal cortex (DLPFC) could attenuate these effects on cognitive and shooting performance in professional female basketball players. However, tDCS did not exert any additional benefits compared to sham.Abbreviations: tDCS: transcranial direct current stimulation; a-tDCS: anodal transcranial direct current stimulation; PFC: prefrontal cortex; DLPFC: dorsolateral prefrontal cortex; PCT: prolonged cognitive task; TT: time trial; RT: response time; NASA-TLX: National Aeronautics and Space Administration Task Load Index; RPE: ratings of perceived exertion; CR-10 scale: category rating scale; EEG: electroencephalogram; AU: arbitrary units.

Contextualised peak periods of play in English Premier League matches.

The present study aimed to determine the physical-tactical trends of elite players/teams during peak 1-, 3- and 5-min periods of match-play. A total of 50 English Premier League matches (n = 583 player observations) were analysed by coding the players' physical-tactical activities through the synchronisation of tracking data and video. The contextualised data showed that during the peak periods (i.e., the most demanding passage of play), players/teams covered the largest distances for 'Recovery Run' (28-37%) out of possession and 'Support Play' (9-13%) in possession. In the following periods, players covered less high-intensity distance versus the average with a more pronounced decline in the next 1-min period than longer duration 3- and 5-min periods (48% vs ~25-30%, ES: 0.4-0.5, P < 0.01); team data showed similar trends with different relative patterns (31% vs 17-30%, ES: 0.5-0.8, P < 0.01). After peak periods, players/teams performed 20-53% less high-intensity distances for 'Covering' and 'Recovery Run' (ES: 0.2-0.7, P < 0.01) out of possession. However, players covered 28-91% less distance for 'Run with Ball' (ES: 0.1-0.5, P < 0.05) when in possession. Some physical-tactical actions exhibited inconsistency in different time durations of the next periods; however, these physical-tactical data were position-specific. This may signify that each position has certain physical-tactical actions to execute even after the peak periods, especially when they are tactically required to do so. As the data demonstrates unique physical-tactical trends of players/teams during the peak and next periods of play, this could help practitioners prescribe position- and player-specific drills, and better understand transient decrements in high-intensity running after intense passages of play.

Tapwater Exposures, Effects Potential, and Residential Risk Management in Northern Plains Nations.

In the United States (US), private-supply tapwater (TW) is rarely monitored. This data gap undermines individual/community risk-management decision-making, leading to an increased probability of unrecognized contaminant exposures in rural and remote locations that rely on private wells. We assessed point-of-use (POU) TW in three northern plains Tribal Nations, where ongoing TW arsenic (As) interventions include expansion of small community water systems and POU adsorptive-media treatment for Strong Heart Water Study participants. Samples from 34 private-well and 22 public-supply sites were analyzed for 476 organics, 34 inorganics, and 3 in vitro bioactivities. 63 organics and 30 inorganics were detected. Arsenic, uranium (U), and lead (Pb) were detected in 54%, 43%, and 20% of samples, respectively. Concentrations equivalent to public-supply maximum contaminant level(s) (MCL) were exceeded only in untreated private-well samples (As 47%, U 3%). Precautionary health-based screening levels were exceeded frequently, due to inorganics in private supplies and chlorine-based disinfection byproducts in public supplies. The results indicate that simultaneous exposures to co-occurring TW contaminants are common, warranting consideration of expanded source, point-of-entry, or POU treatment(s). This study illustrates the importance of increased monitoring of private-well TW, employing a broad, environmentally informative analytical scope, to reduce the risks of unrecognized contaminant exposures.

External and Internal Training Loads for Intensive and Extensive Tactical-Conditioning in Soccer Small Sided Games.

This study aimed to investigate the external (ETLs; 15-Hz GPS unit coupled with a 100 Hz tri-axial accelerometer) and internal training loads (ITLs; session-RPE method) of 18 elite U20 soccer players (19 ± 1.0 years, 178 ± 8 cm, 71 ± 7 kg) undertaking a tactical-conditioning training program with special reference to small-sided games (SSGs). The SSGs used in this program were either extensive (SSG-extensive) or intensive (SSG-intensive) training sessions, that were alternated within the assessed weeks. Tactical principles of the game influenced the aim of the technical-tactical content. Total distance (TDR; ES: 1.17), and a very high-speed running distance (HSR; ES: 0.96) were greater in SSG-extensive vs. SSG-intensive. However, no meaningful difference was found for accelerations (ACC; ES: 0.12) and decelerations (DEC; ES: 0.08). However, a higher perceived intensity (session-RPE; ES: 0.62) and greater ITLs (ES: 0.27) were found for SSG-intensive. These findings suggest that coaches should prescribe SSG training sessions not only considering the usual variables (rules, player numbers, etc.). The current data indicate that the tactical objective of SSGs in relation to exercise bout duration and rest intervals should be considered, while implementing a multi-dimensional training monitoring program during SSG tactical-conditioning training sessions, integrating ETL and ITL variables to gain a better understanding of training responses.

Potential health effects of contaminant mixtures from point and nonpoint sources on fish and frogs in the New Jersey Pinelands.

Aquatic ecosystems convey complex contaminant mixtures from anthropogenic pollution on a global scale. Point (e.g., municipal wastewater) and nonpoint sources (e.g., stormwater runoff) are both drivers of contaminant mixtures in aquatic habitats. The objectives of this study were to identify the contaminant mixtures present in surface waters impacted by both point and nonpoint sources, to determine if aquatic biota (amphibian and fish) health effects (testicular oocytes and parasites) occurred at these sites, and to understand if differences in biological and chemical measures existed between point (on-stream) and nonpoint sources (off-stream). To accomplish this, water chemistry, fishes, and frogs were collected from 21 sites in the New Jersey Pinelands, United States. Off-stream sites consisted of 3 reference and 10 degraded wetlands. On-stream sites consisted of two reference lakes and six degraded streams/lakes (four sites above and two sites below wastewater outfalls). Surface water was collected four times at each site and analyzed for 133 organic and inorganic contaminants. One native and five non-native fish species were collected from streams/lakes and native green frogs from wetlands (ponds and stormwater basins). Limited differences in contaminant concentrations were observed in reference and degraded wetlands but for streams/lakes, results indicated that landscape alteration, (upland agricultural and developed land) was the primary driver of contaminant concentrations rather than municipal wastewater. Incidence of estrogenic endocrine disruption (intersex) was species dependent with the highest prevalence observed in largemouth bass and black crappie and the lowest prevalence observed in green frogs and tessellated darters. Parasite prevalence was site and species dependent. Prevalence of eye parasites increased with increasing concentrations of industrial, mycotoxin, and cumulative inorganic contaminants. These findings are critical to support the conservation, protection, and management of a wide range of aquatic species in the Pinelands and elsewhere as habitat loss, alteration, and fragmentation increase with increasing development.

Neuropsychological evaluation and rehabilitation in multiple sclerosis (NEuRoMS): protocol for a mixed-methods, multicentre feasibility randomised controlled trial.

BACKGROUND: Cognitive problems affect up to 70% of people with multiple sclerosis (MS), which can negatively impact mood, ability to work, and quality of life. Addressing cognitive problems is a top 10 research priority for people with MS. Our ongoing research has systematically developed a cognitive screening and management pathway (NEuRoMS) tailored for people with MS, involving a brief cognitive evaluation and rehabilitation intervention. The present study aims to assess the feasibility of delivering the pathway and will inform the design of a definitive randomised controlled trial (RCT) to investigate the clinical and cost-effectiveness of the intervention and eventually guide its clinical implementation. METHODS: The feasibility study is in three parts. Part 1 involves an observational study of those who receive screening and support for cognitive problems, using routinely collected clinical data. Part 2 is a two-arm, parallel group, multicentre, feasibility RCT with a nested fidelity evaluation. This part will evaluate the feasibility of undertaking a definitive trial comparing the NEuRoMS intervention plus usual care to usual care only, amongst people with MS with mild cognitive problems (n = 60). In part 3, semi-structured interviews will be undertaken with participants from part 2 (n = 25), clinicians (n = 9), and intervention providers (n = 3) involved in delivering the NEuRoMS cognitive screening and management pathway. MS participants will be recruited from outpatient clinics at three UK National Health Service hospitals. DISCUSSION: Timely screening and effective management of cognitive problems in MS are urgently needed due to the detrimental consequences of cognitive problems on people with MS, the healthcare system, and wider society. The NEuRoMS intervention is based on previous and extant literature and has been co-constructed with relevant stakeholders. If effective, the NEuRoMS pathway will facilitate timely identification and management of cognitive problems in people with MS. TRIAL REGISTRATION: ISRCTN11203922 . Prospectively registered on 09.02.2021.