Musculoskeletal injury epidemiology in law enforcement and firefighter recruits during physical training: a systematic review

Objectives: Report the injury epidemiology of law enforcement and firefighter recruits. Design: A systematic epidemiological review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines was completed. Data sources: Five online databases were searched from database inception to 5 May 2021. Eligibility criteria for selecting studies: Prospective and retrospective studies that reported data on musculoskeletal injuries sustained by law enforcement or firefighter recruits were included. We reported on all components of injury where data were available. All injury incidence rates were calculated as per 1000 training days (Poisson 95% CI) to allow comparisons between studies. Study quality was assessed using the Joanna Briggs Institute Quality Assessment Checklist for Prevalence Studies. Results: No studies reporting firefighter recruits were identified. Eight published studies that reported on injuries to law enforcement recruits were identified. The studies were all low quality, and the credibility of the evidence was assessed as very low. Seven studies reported medical attention injuries, and one study reported the number of medical withdrawals from a recruit training programme. The prevalence of law enforcement recruits with medical attention injuries ranged from 13.7% to 24.5%. The overall medical attention injury incidence rate for law enforcement recruits ranged from 1.67 injuries per 1000 training days (Poisson 95% CI 1.00 to 2.34 injuries per 1000 training days) to 4.24 injuries per 1000 training days (Poisson 95% CI 2.97 to 5.51 injuries per 1000 training days). Conclusion: This review reported the prevalence and incidence rates for musculoskeletal injuries in law enforcement officers. However, the credibility of the evidence is very low

Epidemiology of musculoskeletal injury in military recruits: A systematic review and meta-analysis

Background: Injuries are a common occurrence in military recruit training, however due to differences in the capture of training exposure, injury incidence rates are rarely reported. Our aim was to determine the musculoskeletal injury epidemiology of military recruits, including a standardised injury incidence rate. Methods: Epidemiological systematic review following the PRISMA 2020 guidelines. Five online databases were searched from database inception to 5th May 2021. Prospective and retrospective studies that reported data on musculoskeletal injuries sustained by military recruits after the year 2000 were included. We reported on the frequency, prevalence and injury incidence rate. Incidence rate per 1000 training days (Exact 95% CI) was calculated using meta-analysis to allow comparisons between studies. Observed heterogeneity (e.g., training duration) precluded pooling of results across countries. The Joanna Briggs Institute Quality Assessment Checklist for Prevalence Studies assessed study quality. Results: This review identified 41 studies comprising 451,782 recruits. Most studies (n = 26; 63%) reported the number of injured recruits, and the majority of studies (n = 27; 66%) reported the number of injuries to recruits. The prevalence of recruits with medical attention injuries or time-loss injuries was 22.8% and 31.4%, respectively. Meta-analysis revealed the injury incidence rate for recruits with a medical attention injury may be as high as 19.52 injuries per 1000 training days; and time-loss injury may be as high as 3.97 injuries per 1000 training days. Longer recruit training programs were associated with a reduced injury incidence rate (p = 0.003). The overall certainty of the evidence was low per a modified GRADE approach. Conclusion: This systematic review with meta-analysis highlights a high musculoskeletal injury prevalence and injury incidence rate within military recruits undergoing basic training with minimal improvement observed over the past 20 years. Longer training program, which may decrease the degree of overload experienced by recruit, may reduce injury incidence rates. Unfortunately, reporting standards and reporting consistency remain a barrier to generalisability. Trial registration: PROSPERO (Registration number: CRD42021251080)

Oligodeoxynucleotides ODN 2006 and M362 Exert Potent Adjuvant Effect through TLR-9/-6 Synergy to Exaggerate Mammaglobin-A Peptide Specific Cytotoxic CD8+T Lymphocyte Responses against Breast Cancer Cells

Mammaglobin-A (MamA) is overexpressed in 40–80% of all human breast cancers. Recent phase I clinical trials of the MamA DNA vaccine showed encouraging safety outcomes. However, this vaccine elicited only a modest increase in MamA specific CD8+T lymphocyte (CTL) activation. As vaccine adjuvants play a critical role in enhancing the immunotherapeutic efficiency of vaccines, we tested the potential role of three synthetic CpG oligodeoxynucleotides (ODN2216—class A ODN, ODN2006—class B ODN, and ODN M362—class C ODN) to further enhance MamA specific CTL responses. Towards this, naïve CD8+T cells were obtained from healthy HLA-A2+ human donors. The HLA-A2 specific immunodominant epitope of MamA, MamA2.1 (LIYDSSLCDL), was utilized to activate naïve CD8+T cells. The THP-1 (HLA-A2+) cells were used as antigen presenting cells to stimulate naïve CD8+T cells along with (or without) co-treatment of various ODNs mentioned above. Activation of naïve CD8+T cells with the MamA2.1 peptide along with ODNs demonstrated enhanced MamA specific CTL mediated cytotoxicity on AU565 (HLA-A+/MamA+) breast cancer cells following co-treatment with ODN2006 and M362 compared to ODN2216 or MamA2.1 peptide alone. However, no significant cytotoxicity was noted upon treatment of MamA2.1 activated CTLs on MCF7 (HLA-A+/MamA−) cells, suggesting that the activation of CTLs is specific to the MamA antigen. Functional characterization studies demonstrated specific IL-12 mediated cross-talk between TLR-6 and -9 in THP-1 cells following stimulation with ODN2006 and M362, which was critical for the final cytotoxic activation of CD8+T lymphocytes. Based on these data, we conclude that ODN2006 and ODN M362 exerted a strong adjuvant effect through induction of the initial innate immune response through TLR9 upregulation followed by enhanced MamA specific CTL dependent adaptive immune responses. Our current data provide evidence for the application of Class-B/-C-CpG-ODNs as potential vaccine adjuvants towards enhancing the success of MamA based breast cancer vaccination

Uncertainties in mitigating aviation non-CO2 emissions for climate and air quality using hydrocarbon fuels

The uncertainties over the effects of aviation non-CO2 emissions on climate and air quality are assessed in the context of potential mitigation measures for liquid hydrocarbon fuels. Aviation non-CO2 emissions that affect climate include nitrogen oxides (NOx), aerosol particles (soot and sulphur-based), and water vapour. Water vapour and aerosols have small direct radiative effects but are also involved in the formation of contrails and contrail cirrus, currently, the largest non-CO2 effect on climate. These non-CO2 effects on climate are quantified with low confidence, compared to that of CO2, which is quantified with high confidence. The sign of the NOx radiative effects may change from positive to negative. The effects of soot and sulphur emissions on cloudiness are very poorly understood and studies indicate forcings that range from large negative through to small positive. NOx and soot emissions can be reduced through changes in combustion technology but have tradeoffs with each other and CO2. Soot can also be reduced through reduced aromatic content of fuels. In all cases, there are complex choices to be made because of tradeoffs between species, and CO2. Contrail cirrus and soot aerosol–cloud interactions potentially have opposing signs but are both related to soot emissions (at present) and need to be considered together in mitigation strategies. Because of the uncertainties and tradeoffs involved, it is problematic to recommend definitive courses of action on aviation non-CO2 emissions since they may be of limited effect or have unintended consequences. Aviation's non-CO2 effects on climate are short-term, as opposed to those of CO2, which last millennia. If aviation is to contribute towards restricting anthropogenic surface warming to 1.5 or 2 °C then reduction of emissions of CO2 from fossil fuels remains the top priority. In terms of air quality, the situation is more straightforward with emissions standards being set by the International Civil Aviation Organization for NOx and non-volatile particulate matter (and other minor species), which need to be complied with

CXCR2 and CXCL4 regulate survival and self-renewal of hematopoietic stem/progenitor cells

The regulation of hematopoietic stem cell (HSC) survival and self-renewal within the bone marrow (BM) niche is not well understood. We therefore investigated global transcriptomic profiling of normal human hematopoietic stem/progenitor cells, revealing that several chemokine ligands (CXCL1-4, CXCL6, CXCL10, CXCL11, CXCL13) were up-regulated in human quiescent CD34+Hoescht-Pyronin Y- and primitive CD34+38-, as compared to proliferating CD34+Hoechst+Pyronin Y+ and CD34+38+ stem/progenitor cells. This suggested that chemokines may play an important role in the homeostasis of HSCs. In human CD34+ hematopoietic cells, knock-down of CXCL4 or pharmacological inhibition of the chemokine receptor CXCR2, significantly decreased cell viability and colony forming cell (CFC) potential. Studies on Cxcr2-/- mice demonstrated enhanced BM and spleen cellularity, with significantly increased numbers of HSC, hematopoietic progenitor cell (HPC)-1, HPC-2 and Lin-Sca-1+c-Kit+ sub-populations. Cxcr2-/- stem/progenitor cells showed reduced self-renewal capacity as measured in serial transplantation assays. Parallel studies on Cxcl4 demonstrated reduced numbers of CFC in primary and secondary assays following knock-down in murine c-Kit+ cells and Cxcl4-/- mice showed a decrease in HSC and reduced self-renewal capacity after secondary transplantation. These data demonstrate that the CXCR2 network and CXCL4 play a role in the maintenance of normal hematopoietic stem/progenitor cell fates, including survival and self-renewal

Effects of a high-dose 24-h infusion of tranexamic acid on death and thromboembolic events in patients with acute gastrointestinal bleeding (HALT-IT): an international randomised, double-blind, placebo-controlled trial

Background: Tranexamic acid reduces surgical bleeding and reduces death due to bleeding in patients with trauma. Meta-analyses of small trials show that tranexamic acid might decrease deaths from gastrointestinal bleeding. We aimed to assess the effects of tranexamic acid in patients with gastrointestinal bleeding. Methods: We did an international, multicentre, randomised, placebo-controlled trial in 164 hospitals in 15 countries. Patients were enrolled if the responsible clinician was uncertain whether to use tranexamic acid, were aged above the minimum age considered an adult in their country (either aged 16 years and older or aged 18 years and older), and had significant (defined as at risk of bleeding to death) upper or lower gastrointestinal bleeding. Patients were randomly assigned by selection of a numbered treatment pack from a box containing eight packs that were identical apart from the pack number. Patients received either a loading dose of 1 g tranexamic acid, which was added to 100 mL infusion bag of 0·9% sodium chloride and infused by slow intravenous injection over 10 min, followed by a maintenance dose of 3 g tranexamic acid added to 1 L of any isotonic intravenous solution and infused at 125 mg/h for 24 h, or placebo (sodium chloride 0·9%). Patients, caregivers, and those assessing outcomes were masked to allocation. The primary outcome was death due to bleeding within 5 days of randomisation; analysis excluded patients who received neither dose of the allocated treatment and those for whom outcome data on death were unavailable. This trial was registered with Current Controlled Trials, ISRCTN11225767, and ClinicalTrials.gov, NCT01658124. Findings: Between July 4, 2013, and June 21, 2019, we randomly allocated 12 009 patients to receive tranexamic acid (5994, 49·9%) or matching placebo (6015, 50·1%), of whom 11 952 (99·5%) received the first dose of the allocated treatment. Death due to bleeding within 5 days of randomisation occurred in 222 (4%) of 5956 patients in the tranexamic acid group and in 226 (4%) of 5981 patients in the placebo group (risk ratio [RR] 0·99, 95% CI 0·82–1·18). Arterial thromboembolic events (myocardial infarction or stroke) were similar in the tranexamic acid group and placebo group (42 [0·7%] of 5952 vs 46 [0·8%] of 5977; 0·92; 0·60 to 1·39). Venous thromboembolic events (deep vein thrombosis or pulmonary embolism) were higher in tranexamic acid group than in the placebo group (48 [0·8%] of 5952 vs 26 [0·4%] of 5977; RR 1·85; 95% CI 1·15 to 2·98). Interpretation: We found that tranexamic acid did not reduce death from gastrointestinal bleeding. On the basis of our results, tranexamic acid should not be used for the treatment of gastrointestinal bleeding outside the context of a randomised trial

The study of women, infant feeding and type 2 diabetes after GDM pregnancy and growth of their offspring (SWIFT Offspring study): prospective design, methodology and baseline characteristics

Abstract Background Breastfeeding is associated with reduced risk of becoming overweight or obese later in life. Breastfed babies grow more slowly during infancy than formula-fed babies. Among offspring exposed in utero to maternal glucose intolerance, prospective data on growth during infancy have been unavailable. Thus, scientific evidence is insufficient to conclude that breastfeeding reduces the risk of obesity among the offspring of diabetic mothers (ODM). To address this gap, we devised the Study of Women, Infant Feeding and Type 2 Diabetes after GDM Pregnancy and Growth of their Offspring, also known as the SWIFT Offspring Study. This prospective, longitudinal study recruited mother-infant pairs from the SWIFT Study, a prospective study of women with recent gestational diabetes mellitus (GDM). The goal of the SWIFT Offspring Study is to determine whether breastfeeding intensity and duration, compared with formula feeding, are related to slower growth of GDM offspring during the first year life. This article details the study design, participant eligibility, data collection, and methodologies. We also describe the baseline characteristics of the GDM mother-infant pairs. Methods The study enrolled 466 mother-infant pairs among GDM deliveries in northern California from 2009–2011. Participants attended three in-person study exams at 6–9 weeks, 6 months and 12 months after delivery for infant anthropometry (head circumference, body weight, length, abdominal circumference and skinfold thicknesses), as well as maternal anthropometry (body weight, waist circumference and percent body fat). Mothers also completed questionnaires on health and lifestyle behaviors, including infant diet, sleep and temperament. Breastfeeding intensity and duration were assessed via several sources (diaries, telephone interviews, monthly mailings and in-person exams) from birth through the first year of life. Pregnancy course, clinical perinatal and newborn outcomes were obtained from health plan electronic medical records. Infant saliva samples were collected and stored for genetics studies. Discussion This large, racially and ethnically diverse cohort of GDM offspring will enable evaluation of the relationship of infant feeding to growth during infancy independent of perinatal characteristics, sociodemographics and other risk factors. The longitudinal design provides the first quantitative measures of breastfeeding intensity and duration among GDM offspring during early life