Real-world community hospital hyperglycemia management in noncritically ill, type 2 diabetic patients: a comparison between basal-bolus insulin and correctional insulin.

Purpose: This study evaluated the safety and efficacy of two insulin regimens for inpatient hyperglycemia management: combination short-plus long-acting insulin (basal-bolus insulin regimen, BBIR) vs. short-acting insulin only (correctional insulin only regimen, CIOR). Methods: Chart reviews identified noncritically ill patients with pre-existing type 2 diabetes mellitus receiving insulin injections. Study participants (N = 138) were divided into BBIR (N = 104) and CIOR (N = 34) groups. Data for the entire duration of each patient's stay were analyzed. Results: The primary outcome of percent hyperglycemic days was higher in BBIR vs. CIOR (3.97 ± 0.33% vs. 1.22 ± 0.38%). The safety outcome of percent hypoglycemic events was not different between BBIR and CIOR (0.78 ± 0.22% vs. 0.53 ± 0.37%). Regarding secondary outcomes, the percentage of euglycemic days was lower in BBIR vs. CIOR (26.74 ± 2.97% vs. 40.98 ± 5.91%). Overall blood glucose (BG) and daily insulin dose were higher in BBIR vs. CIOR (231.43 ± 5.37 vs. 195.55 ± 6.25 mg/dL and 41.36 ± 3.07 vs. 5.02 ± 0.68 units, respectively). Insulin regimen-associated differences in hyperglycemia and daily insulin dose persisted after adjusting for covariates. Conclusion: Our observations linking BBIR to worse glycemic outcomes differ from those reported in the randomized controlled Rabbit 2 and Rabbit 2 Surgery trials. This discrepancy can be partly explained by the fact that BBIR patients displayed worse glycemic baselines. Also, there was no diabetes stewardship team to monitor BG and modify insulin therapy, which is relevant since achieving euglycemia in BBIR patients requires more dose adjustments. This study highlights challenges with standard inpatient glycemic management and calls for further research assessing the benefits of pharmacist-led diabetes stewardship.

Antibody Responses to the SARS-CoV-2 Ancestral Strain and Omicron Variants in Moderna mRNA-1273 Vaccinated Active-Duty US Navy Sailors and Marines.

Omicron and its subvariants have steadily gained greater capability of immune escape compared to other variants of concern, resulting in an increased incidence of reinfections even among vaccinated individuals. We evaluated the antibody response to Omicron BA.1, BA.2, and BA.4/5 in US military members vaccinated with the primary 2-dose series of Moderna mRNA-1273 in a cross-sectional study. While nearly all vaccinated participants had sustained spike (S) IgG and neutralizing antibodies (ND50) to the ancestral strain, only 7.7% participants had detectable ND50 to Omicron BA.1 at 8 months postvaccination. The neutralizing antibody response to BA.2 and BA.5 was similarly reduced. The reduced antibody neutralization of Omicron correlated with the decreased antibody binding to the receptor-binding domain. The participants' seropositivity to the nuclear protein positively correlated with ND50. Our data emphasizes the need for continuous vigilance in monitoring for emerging variants and the need to identify potential alternative targets for vaccine design.

SARS-CoV-2 Transmission among Marine Recruits during Quarantine.

BACKGROUND: The efficacy of public health measures to control the transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has not been well studied in young adults. METHODS: We investigated SARS-CoV-2 infections among U.S. Marine Corps recruits who underwent a 2-week quarantine at home followed by a second supervised 2-week quarantine at a closed college campus that involved mask wearing, social distancing, and daily temperature and symptom monitoring. Study volunteers were tested for SARS-CoV-2 by means of quantitative polymerase-chain-reaction (qPCR) assay of nares swab specimens obtained between the time of arrival and the second day of supervised quarantine and on days 7 and 14. Recruits who did not volunteer for the study underwent qPCR testing only on day 14, at the end of the quarantine period. We performed phylogenetic analysis of viral genomes obtained from infected study volunteers to identify clusters and to assess the epidemiologic features of infections. RESULTS: A total of 1848 recruits volunteered to participate in the study; within 2 days after arrival on campus, 16 (0.9%) tested positive for SARS-CoV-2, 15 of whom were asymptomatic. An additional 35 participants (1.9%) tested positive on day 7 or on day 14. Five of the 51 participants (9.8%) who tested positive at any time had symptoms in the week before a positive qPCR test. Of the recruits who declined to participate in the study, 26 (1.7%) of the 1554 recruits with available qPCR results tested positive on day 14. No SARS-CoV-2 infections were identified through clinical qPCR testing performed as a result of daily symptom monitoring. Analysis of 36 SARS-CoV-2 genomes obtained from 32 participants revealed six transmission clusters among 18 participants. Epidemiologic analysis supported multiple local transmission events, including transmission between roommates and among recruits within the same platoon. CONCLUSIONS: Among Marine Corps recruits, approximately 2% who had previously had negative results for SARS-CoV-2 at the beginning of supervised quarantine, and less than 2% of recruits with unknown previous status, tested positive by day 14. Most recruits who tested positive were asymptomatic, and no infections were detected through daily symptom monitoring. Transmission clusters occurred within platoons. (Funded by the Defense Health Agency and others.).

Dysfunction of homeostatic control of dopamine by astrocytes in the developing prefrontal cortex leads to cognitive impairments.

Astrocytes orchestrate neural development by powerfully coordinating synapse formation and function and, as such, may be critically involved in the pathogenesis of neurodevelopmental abnormalities and cognitive deficits commonly observed in psychiatric disorders. Here, we report the identification of a subset of cortical astrocytes that are competent for regulating dopamine (DA) homeostasis during postnatal development of the prefrontal cortex (PFC), allowing for optimal DA-mediated maturation of excitatory circuits. Such control of DA homeostasis occurs through the coordinated activity of astroglial vesicular monoamine transporter 2 (VMAT2) together with organic cation transporter 3 and monoamine oxidase type B, two key proteins for DA uptake and metabolism. Conditional deletion of VMAT2 in astrocytes postnatally produces loss of PFC DA homeostasis, leading to defective synaptic transmission and plasticity as well as impaired executive functions. Our findings show a novel role for PFC astrocytes in the DA modulation of cognitive performances with relevance to psychiatric disorders.

The properties of Msh2-Msh6 ATP binding mutants suggest a signal amplification mechanism in DNA mismatch repair.

DNA mismatch repair (MMR) corrects mispaired DNA bases and small insertion/deletion loops generated by DNA replication errors. After binding a mispair, the eukaryotic mispair recognition complex Msh2-Msh6 binds ATP in both of its nucleotide-binding sites, which induces a conformational change resulting in the formation of an Msh2-Msh6 sliding clamp that releases from the mispair and slides freely along the DNA. However, the roles that Msh2-Msh6 sliding clamps play in MMR remain poorly understood. Here, using Saccharomyces cerevisiae, we created Msh2 and Msh6 Walker A nucleotide-binding site mutants that have defects in ATP binding in one or both nucleotide-binding sites of the Msh2-Msh6 heterodimer. We found that these mutations cause a complete MMR defect in vivo The mutant Msh2-Msh6 complexes exhibited normal mispair recognition and were proficient at recruiting the MMR endonuclease Mlh1-Pms1 to mispaired DNA. At physiological (2.5 mm) ATP concentration, the mutant complexes displayed modest partial defects in supporting MMR in reconstituted Mlh1-Pms1-independent and Mlh1-Pms1-dependent MMR reactions in vitro and in activation of the Mlh1-Pms1 endonuclease and showed a more severe defect at low (0.1 mm) ATP concentration. In contrast, five of the mutants were completely defective and one was mostly defective for sliding clamp formation at high and low ATP concentrations. These findings suggest that mispair-dependent sliding clamp formation triggers binding of additional Msh2-Msh6 complexes and that further recruitment of additional downstream MMR proteins is required for signal amplification of mispair binding during MMR.

Atmospheric pressure non-thermal plasma exposure reduces Pseudomonas aeruginosa lipopolysaccharide toxicity in vitro and in vivo.

Lipopolysaccharide (LPS) is an endotoxin composed of a polysaccharide and lipid component. It is intrinsically responsible for the pathogenicity of Gram-negative bacteria and is involved in the development of bacterial sepsis. Atmospheric pressure non-thermal plasma is proposed as a potential new approach for the treatment of infected tissue such as chronic wounds, with both antibacterial and wound-healing activities extensively described. Using both the RAW264.7 murine macrophage cell line in vitro assays and the Galleria mellonella insect in vivo toxicity model, the effect non-thermal plasma exposure on LPS-mediated toxicity has been characterised. Short (60 s) non-thermal plasma exposures of Pseudomonas aeruginosa conditioned growth media, membrane lysates and purified P. aeruginosa LPS, resulted in a substantial detoxification and reduction of LPS-induced cytotoxicity in RAW264.7 murine macrophages. Non-thermal plasma exposure (60 s) of purified P. aeruginosa LPS led to a significant (p < 0.05) improvement in the G. mellonella health index (GHI) score, a measure of in vivo toxicity. These findings demonstrate the ability of short plasma exposures to significantly reduce LPS-induced cytotoxicity both in vitro and in vivo; attenuating the toxicity of this important virulence factor intrinsic to the pathogenicity of Gram-negative bacteria.

Frequency-dependent impedance and surface waves on the boundary of a stratified dielectric medium.

We analyse waves propagating along the interface between half-spaces filled with a perfect dielectric and a Lorentz material. We show that the corresponding interface condition leads to a generalization of the classical Leontovich condition on the boundary of a dielectric half-space. We study when this condition supports propagation of (dispersive) surface waves. We derive the related dispersion relation for waves along the boundary of a stratified half-space and determine the relationship between the loss parameter, frequency and wavenumber for which interfacial waves exist. This article is part of the theme issue 'Modelling of dynamic phenomena and localization in structured media (part 1)'.

Neurophysiological Characterization of a Non-Human Primate Model of Traumatic Spinal Cord Injury Utilizing Fine-Wire EMG Electrodes.

This study aims to characterize traumatic spinal cord injury (TSCI) neurophysiologically using an intramuscular fine-wire electromyography (EMG) electrode pair. EMG data were collected from an agonist-antagonist pair of tail muscles of Macaca fasicularis, pre- and post-lesion, and for a treatment and control group. The EMG signals were decomposed into multi-resolution subsets using wavelet transforms (WT), then the relative power (RP) was calculated for each individual reconstructed EMG sub-band. Linear mixed models were developed to test three hypotheses: (i) asymmetrical volitional activity of left and right side tail muscles (ii) the effect of the experimental TSCI on the frequency content of the EMG signal, (iii) and the effect of an experimental treatment. The results from the electrode pair data suggested that there is asymmetry in the EMG response of the left and right side muscles (p-value < 0.001). This is consistent with the construct of limb dominance. The results also suggest that the lesion resulted in clear changes in the EMG frequency distribution in the post-lesion period with a significant increment in the low-frequency sub-bands (D4, D6, and A6) of the left and right side, also a significant reduction in the high-frequency sub-bands (D1 and D2) of the right side (p-value < 0.001). The preliminary results suggest that using the RP of the EMG data, the fine-wire intramuscular EMG electrode pair are a suitable method of monitoring and measuring treatment effects of experimental treatments for spinal cord injury (SCI).

Sequencing the Biology of Entry: The Retroviral env Gene.

The surface envelope protein of any virus is major determinant of the host cell that is infected and as a result a major determinant of viral pathogenesis. Retroviruses have a single surface protein named Env. It is a trimer of heterodimers and is responsible for binding to the host cell receptor and mediating fusion between the viral and host membranes. In this review we will discuss the history of the discovery of the avian leukosis virus (ALV) and human immunodeficiency virus type 1 (HIV-1) Env proteins and their receptor specificity, comparing the many differences but having some similarities. Much of the progress in these fields has relied on viral genetics and genetic polymorphisms in the host population. A special feature of HIV-1 is that its persistent infection in its human host, to the point of depleting its favorite target cells, allows the virus to evolve new entry phenotypes to expand its host range into several new cell types. This variety of entry phenotypes has led to confusion in the field leading to the major form of entry phenotype of HIV-1 being overlooked until recently. Thus an important part of this story is the description and naming of the most abundant entry form of the virus: R5 T cell-tropic HIV-1.

Venous Thromboembolism Rates in Transferred Patients: A Cross-Sectional Study.

BACKGROUND: Patients undergoing a transfer during a hospitalization may be more likely to be diagnosed with a venous thromboembolism (VTE) than patients who are not transferred. OBJECTIVE: To determine whether transferred patients have an increased prevalence of VTE diagnosis. DESIGN: This was a cross-sectional study comparing VTE diagnosis rates between transferred patients and non-transferred patients. For the years 2012-2014, the University HealthSystem Consortium database of multiple community and academic medical centers throughout the United States was parsed using ICD-9 VTE diagnosis codes and patient's point of origin. PATIENTS: Patients were included in the analysis as transferred patients if their point of origin was a skilled nursing facility, another acute care facility or another facility. Non-transferred patients were those whose point of origin was a clinic or those with a non-facility point of origin. MAIN MEASURES: The primary comparison of VTE prevalence during hospitalization between transferred and non-transferred patients in the years 2012-2014. Subgroup analysis looked at level I trauma status and case mix index (CMI) to determine whether these had an effect on VTE prevalence. KEY RESULTS: From 2012 to 2014, a total of 225 unique hospitals and 12,036,029 patients were analyzed, and the prevalence of VTE in transferred patients and non-transferred patients was 3.43% and 1.91% (RR 1.80; 95% CI 1.78-1.81; P <0.001), respectively. VTE prevalence in transferred versus non-transferred patients at level I trauma centers was 3.42% versus 1.88% (RR = 1.82; 95% CI 1.80-1.85; P <0.001). The 3-year average CMI of transferred versus non-transferred patients was 3.53 versus 2.26 (P < 0.001). CONCLUSIONS: Transferred patients have a higher prevalence of VTE than non-transferred patients, regardless of level I trauma designation. Higher VTE rates in transferred versus non-transferred patients was minimally correlated with CMI.

Activation of Saccharomyces cerevisiae Mlh1-Pms1 Endonuclease in a Reconstituted Mismatch Repair System.

Previous studies reported the reconstitution of an Mlh1-Pms1-independent 5' nick-directed mismatch repair (MMR) reaction using Saccharomyces cerevisiae proteins. Here we describe the reconstitution of a mispair-dependent Mlh1-Pms1 endonuclease activation reaction requiring Msh2-Msh6 (or Msh2-Msh3), proliferating cell nuclear antigen (PCNA), and replication factor C (RFC) and a reconstituted Mlh1-Pms1-dependent 3' nick-directed MMR reaction requiring Msh2-Msh6 (or Msh2-Msh3), exonuclease 1 (Exo1), replication protein A (RPA), RFC, PCNA, and DNA polymerase δ. Both reactions required Mg(2+) and Mn(2+) for optimal activity. The MMR reaction also required two reaction stages in which the first stage required incubation of Mlh1-Pms1 with substrate DNA, with or without Msh2-Msh6 (or Msh2-Msh3), PCNA, and RFC but did not require nicking of the substrate, followed by a second stage in which other proteins were added. Analysis of different mutant proteins demonstrated that both reactions required a functional Mlh1-Pms1 endonuclease active site, as well as mispair recognition and Mlh1-Pms1 recruitment by Msh2-Msh6 but not sliding clamp formation. Mutant Mlh1-Pms1 and PCNA proteins that were defective for Exo1-independent but not Exo1-dependent MMR in vivo were partially defective in the Mlh1-Pms1 endonuclease and MMR reactions, suggesting that both reactions reflect the activation of Mlh1-Pms1 seen in Exo1-independent MMR in vivo. The availability of this reconstituted MMR reaction should now make it possible to better study both Exo1-independent and Exo1-dependent MMR.

Phenotypic Correlates of HIV-1 Macrophage Tropism.

UNLABELLED: HIV-1 is typically CCR5 using (R5) and T cell tropic (T-tropic), targeting memory CD4(+) T cells throughout acute and chronic infections. However, viruses can expand into alternative cells types. Macrophage-tropic (M-tropic) HIV-1 variants have evolved to infect macrophages, which have only low levels of surface CD4. Most M-tropic variants have been isolated from the central nervous system during late-stage chronic infection. We used the HIV-1 env genes of well-defined, subject-matched M-tropic and T-tropic viruses to characterize the phenotypic features of the M-tropic Env protein. We found that, compared to T-tropic viruses, M-tropic viruses infect monocyte-derived macrophages (MDMs) on average 28-fold more efficiently, use low-density CD4 more efficiently, have increased sensitivity to soluble CD4 (sCD4), and show trends toward sensitivity to some CD4 binding site antibodies but no difference in sensitivity to antibodies targeting the CD4-bound conformation. M-tropic viruses also displayed a trend toward resistance to neutralization by monoclonal antibodies targeting the V1/V2 region of Env, suggesting subtle changes in Env protein conformation. The paired M- and T-tropic viruses did not differ in autologous serum neutralization, temperature sensitivity, entry kinetics, intrinsic infectivity, or Env protein incorporation. We also examined viruses with modestly increased CD4 usage. These variants have significant sensitivity to sCD4 and may represent evolutionary intermediates. CD4 usage is strongly correlated with infectivity of MDMs over a wide range of CD4 entry phenotypes. These data suggest that emergence of M-tropic HIV-1 includes multiple steps in which a phenotype of increased sensitivity to sCD4 and enhanced CD4 usage accompany subtle changes in Env conformation. IMPORTANCE: HIV-1 typically replicates in CD4(+) T cells. However, HIV-1 can evolve to infect macrophages, especially within the brain. Understanding how CCR5-using macrophage-tropic viruses evolve and differ from CCR5-using T cell-tropic viruses may provide insights into viral evolution and pathogenesis within the central nervous system. We characterized the HIV-1 env viral entry gene from subject-matched macrophage-tropic and T cell-tropic viruses to identify entry features of macrophage-tropic viruses. We observed several differences between T cell-tropic and macrophage-tropic Env proteins, including functional differences with host CD4 receptor engagement and possible changes in the CD4 binding site and V1/V2 region. We also identified viruses with phenotypes between that of "true" macrophage-tropic and T cell-tropic viruses, which may represent evolutionary intermediates in a multistep process to macrophage tropism.

Recurrent jellyfish blooms are a consequence of global oscillations.

A perceived recent increase in global jellyfish abundance has been portrayed as a symptom of degraded oceans. This perception is based primarily on a few case studies and anecdotal evidence, but a formal analysis of global temporal trends in jellyfish populations has been missing. Here, we analyze all available long-term datasets on changes in jellyfish abundance across multiple coastal stations, using linear and logistic mixed models and effect-size analysis to show that there is no robust evidence for a global increase in jellyfish. Although there has been a small linear increase in jellyfish since the 1970s, this trend was unsubstantiated by effect-size analysis that showed no difference in the proportion of increasing vs. decreasing jellyfish populations over all time periods examined. Rather, the strongest nonrandom trend indicated jellyfish populations undergo larger, worldwide oscillations with an approximate 20-y periodicity, including a rising phase during the 1990s that contributed to the perception of a global increase in jellyfish abundance. Sustained monitoring is required over the next decade to elucidate with statistical confidence whether the weak increasing linear trend in jellyfish after 1970 is an actual shift in the baseline or part of an oscillation. Irrespective of the nature of increase, given the potential damage posed by jellyfish blooms to fisheries, tourism, and other human industries, our findings foretell recurrent phases of rise and fall in jellyfish populations that society should be prepared to face.

Epidemiology of meniscal injuries in US high school athletes between 2007 and 2013.

PURPOSE: Knowledge of epidemiologic trends of meniscal injuries in young active populations is limited. Better awareness of injury patterns is a first step to lowering injury rates. Our hypothesis was that meniscal injuries in high school athletes would vary by gender, sport, and type of exposure. METHODS: During the 2007/2008 and 2012/2013 academic years, a large nationally disperse sample of US high schools reported athlete exposure and injury data for 22 sports by having certified athletic trainers complete an internet-based data collection tool. RESULTS: One thousand and eighty-two meniscal injuries were reported during 21,088,365 athlete exposures for an overall injury rate of 5.1 per 100,000 athlete exposures. The overall rate of injury was higher in competition (11.9) than practice (2.7) (RR = 4.4; 95% CI 3.9-5.0), and 12/19 sports showed significantly higher injury rates in competition compared to practice. Of all injuries, 68.0% occurred in boys, yet among the gender-comparable sports of soccer, basketball, track and field, lacrosse, and baseball/softball injury rates were higher for girls than boys (5.5 and 2.5, respectively, RR = 2.2; 95% CI 1.8-2.7). Contact injury represented the most common mechanism (55.9%). Surgery was performed for the majority of injuries (63.8%), and 54.0% of athletes had associated intra-articular knee pathology. CONCLUSIONS: Meniscal injury patterns among high school athletes vary by gender, sport, and type of exposure. Our study is clinically relevant because recognition of distinct differences in these injury patterns will help drive evidence-based, targeted injury prevention strategies and efforts. LEVEL OF EVIDENCE: III.

Jellyfish blooms result in a major microbial respiratory sink of carbon in marine systems.

Jellyfish blooms occur in many estuarine and coastal regions and may be increasing in their magnitude and extent worldwide. Voracious jellyfish predation impacts food webs by converting large quantities of carbon (C), fixed by primary producers and consumed by secondary producers, into gelatinous biomass, which restricts C transfer to higher trophic levels because jellyfish are not readily consumed by other predators. In addition, jellyfish release colloidal and dissolved organic matter (jelly-DOM), and could further influence the functioning of coastal systems by altering microbial nutrient and DOM pathways, yet the links between jellyfish and bacterioplankton metabolism and community structure are unknown. Here we report that jellyfish released substantial quantities of extremely labile C-rich DOM, relative to nitrogen (25.6 ± 31.6 C:1N), which was quickly metabolized by bacterioplankton at uptake rates two to six times that of bulk DOM pools. When jelly-DOM was consumed it was shunted toward bacterial respiration rather than production, significantly reducing bacterial growth efficiencies by 10% to 15%. Jelly-DOM also favored the rapid growth and dominance of specific bacterial phylogenetic groups (primarily γ-proteobacteria) that were rare in ambient waters, implying that jelly-DOM was channeled through a small component of the in situ microbial assemblage and thus induced large changes in community composition. Our findings suggest major shifts in microbial structure and function associated with jellyfish blooms, and a large detour of C toward bacterial CO(2) production and away from higher trophic levels. These results further suggest fundamental transformations in the biogeochemical functioning and biological structure of food webs associated with jellyfish blooms.

Origin of the direct and reflected head of the rectus femoris: an anatomic study.

PURPOSE: This study aimed to define the footprint of the direct and reflected heads of the rectus femoris and the relation of the anterior inferior iliac spine (AIIS) to adjacent neurovascular (lateral circumflex femoral artery and femoral nerve), bony (anterior superior iliac spine [ASIS]), and tendinous structures (iliopsoas). METHODS: Twelve fresh-frozen cadaveric hip joints from 6 cadavers, average age of 44.5 (±9.9) years, were carefully dissected of skin and fascia to expose the muscular, capsular, and bony structures of the anterior hip and pelvis. Using digital calipers, measurements were taken of the footprint of the rectus femoris on the AIIS, superior-lateral acetabulum and hip capsule, and adjacent anatomic structures. RESULTS: The average dimensions of the footprint of the direct head of the rectus femoris were 13.4 mm (±1.7) × 26.0 mm (±4.1), whereas the dimensions of the reflected head footprint were 47.7 mm (±4.4) × 16.8 mm (±2.2). Important anatomic structures, including the femoral nerve, psoas tendon, and lateral circumflex femoral artery, were noted in proximity to the AIIS. The neurovascular structure closest to the AIIS was the femoral nerve (20.8 ± 3.4 mm). CONCLUSIONS: The rectus femoris direct and reflected heads originate over a broad area of the anterolateral pelvis and are in close proximity to critical neurovascular structures, and care must be taken to avoid them during hip arthroscopy. CLINICAL RELEVANCE: A thorough knowledge of the anatomy of the proximal rectus femoris is valuable for any surgical exposure of the anterior hip joint, particularly arthroscopic subspine decompression and open femoroacetabular impingement (FAI) surgery.

Focused deterrence: A protocol for a realist multisite randomised controlled trial for evaluating a violence prevention intervention in the UK.

INTRODUCTION: Focused deterrence (FD) is a frequently cited intervention for preventing violence, particularly against violent urban gangs. The Youth Endowment Fund (YEF) believes it could be effective in the UK, based primarily on research conducted in the US. However, we contend that these studies have inadequate methodological designs, lack of rigorous testing, and small sample sizes. Therefore, the evidence supporting focused deterrence as an effective method, particularly outside the US, is inconclusive. The aim of the protocol is to better understand the potential effects of FD in the context of the UK, using a multisite evaluation experimental design to more closely investigate the evidence of its likely impact. METHODS: We planned a realist randomised controlled trial. The design is focused on a multisite trial consisting of two-arm randomised experiments in five locations. Each trial location will test their implementation of a core programme specified by the funder. The multisite nature will allow us to understand differential impacts between locations, improving the external validity of the results. Participants will be randomly selected from a wider pool of eligible individuals for the intervention. We estimate a sample size of approximately N = 1,700 individuals is required. Based on this pooled sample size, a relative reduction of 26% would be detectable in 80% of trials. The trial is coupled with a formative process evaluation of delivery and fidelity. The formative evaluation will use a mixed methods design. The qualitative aspect will include semi-structured cross-sectional and longitudinal interviews with programme leads, programme delivery team, and programme participants, as well as observations of the meetings between the programme delivery team (i.e., community navigators/mentors) and programme participants. The quantitative data for the formative evaluation will be gathered by the sites themselves and consist of routine outcome performance monitoring using administrative data. Sampling for interviews and observations will vary, with the researchers aiming for a higher number of individuals included in the first round of cross-sectional interviews and retaining as many as possible for repeat interviews and observations. DISCUSSION: This protocol outlines the process and impact evaluation methodology for the most extensive multisite evaluation of focused deterrence to date in the UK. Spanning five distinct sites with seven trials, the evaluation includes a cohort of 2,000 individuals, marking it as the only multisite trial of focused deterrence. Employing an integrated realist evaluation framework, the study uses qualitative and quantitative research methods. The anticipated findings will offer pivotal insights for formulating future violence prevention policies in the UK. They are also expected to contribute significantly to the corpus of literature on violence prevention and intervention evaluation. TRIAL REGISTRATION: Protocol registration: ISRCTN: 11650008 4th June 2023.

Assessment of Cold Atmospheric Pressure Plasma (CAPP) Treatment for Degradation of Antibiotic Residues in Water.

The presence of antibiotic residues in water is linked to the emergence of antibiotic resistance globally and necessitates novel decontamination strategies to minimize antibiotic residue exposure in both the environment and food. A holistic assessment of cold atmospheric pressure plasma technology (CAPP) for ß-lactam antibiotic residue removal is described in this study. CAPP operating parameters including plasma jet voltage, gas composition and treatment time were optimized, with highest ß-lactam degradation efficiencies obtained for a helium jet operated at 6 kV. Main by-products detected indicate pH-driven peroxidation as a main mechanism of CAPP-induced decomposition of ß-lactams. No in vitro hepatocytotoxicity was observed in HepG2 cells following exposure to treated samples, and E. coli exposed to CAPP-degraded ß-lactams did not exhibit resistance development. In surface water, over 50% decrease in antibiotic levels was achieved after only 5 min of treatment. However, high dependence of treatment efficiency on residue concentration, pH and presence of polar macromolecules was observed.

Oil weathering after the Deepwater Horizon disaster led to the formation of oxygenated residues.

Following the Deepwater Horizon disaster, the effect of weathering on surface slicks, oil-soaked sands, and oil-covered rocks and boulders was studied for 18 months. With time, oxygen content increased in the hydrocarbon residues. Furthermore, a weathering-dependent increase of an operationally defined oxygenated fraction relative to the saturated and aromatic fractions was observed. This oxygenated fraction made up >50% of the mass of weathered samples, had an average carbon oxidation state of -1.0, and an average molecular formula of (C(5)H(7)O)(n). These oxygenated hydrocarbon residues were devoid of natural radiocarbon, confirming a fossil source and excluding contributions from recent photosynthate. The incorporation of oxygen into the oil's hydrocarbons, which we refer to as oxyhydrocarbons, was confirmed from the detection of hydroxyl and carbonyl functional groups and the identification of long chain (C(10)-C(32)) carboxylic acids as well as alcohols. On the basis of the diagnostic ratios of alkanes and polycyclic aromatic hydrocarbons, and the context within which these samples were collected, we hypothesize that biodegradation and photooxidation share responsibility for the accumulation of oxygen in the oil residues. These results reveal that molecular-level transformations of petroleum hydrocarbons lead to increasing amounts of, apparently recalcitrant, oxyhydrocarbons that dominate the solvent-extractable material from oiled samples.

Jellyfish life histories: role of polyps in forming and maintaining scyphomedusa populations.

Large population fluctuations of jellyfish occur over a variety of temporal scales, from weekly to seasonal, inter-annual and even decadal, with some regions of the world reported to be experiencing persistent seasonal bloom events. Recent jellyfish research has focussed on understanding the causes and consequences of these population changes, with the vast majority of studies considering the effect of changing environmental variables only on the pelagic medusa. But many of the bloom-forming species are members of the Scyphozoa with complex metagenic life cycles consisting of a sexually reproducing pelagic medusa and asexually reproducing benthic polyp. Recruitment success during the juvenile (planula, polyp and ephyrae) stages of the life cycle can have a major effect on the abundance of the adult (medusa) population, but until very recently, little was known about the ecology of the polyp or scyphistoma phase of the scyphozoan life cycle. The aim of this review is to synthesise the current state of knowledge of polyp ecology by examining (1) the recruitment and metamorphosis of planulae larvae into polyps, (2) survival and longevity of polyps, (3) expansion of polyp populations via asexual propagation and (4) strobilation and recruitment of ephyrae (juvenile medusae). Where possible, comparisons are made with the life histories of other bentho-pelagic marine invertebrates so that further inferences can be made. Differences between tropical and temperate species are highlighted and related to climate change, and populations of the same species (in particular Aurelia aurita) inhabiting different habitats within its geographic range are compared. The roles that polyps play in ensuring the long-term survival of jellyfish populations as well as in the formation of bloom populations are considered, and recommendations for future research are presented.