Search

ObjectivesThis umbrella review aims to summarise the evidence about electronic nicotine delivery systems’ (ENDS) risk and safety health profile to inform ENDS health communication strategies.Data sources and study selectionSix databases were searched for systematic reviews presenting evidence on ENDS-related health effects. Ninety reviews divided into five categories were included: toxicity=20, health effects=40, role in smoking cessation=24, role in transition to combustible cigarettes (CCs)=13 and industry marketing claims=4.Data extractionFindings were synthesised in narrative summaries. Meta-analyses were conducted by study type when appropriate. Quality assessment was conducted using the Measurement Tool to Assess Systematic Reviews. The Institute of Medicine’s Levels of Evidence Framework was used to classify the evidence into high-level, moderate, limited-suggestive and limited-not-conclusive.Data synthesisWe found high-level evidence that ENDS exposes users to toxic substances; increases the risk of respiratory disease; leads to nicotine dependence; causes serious injuries due to explosion or poisoning; increases smoking cessation in clinical trials but not in observational studies; increases CC initiation; and exposure to ENDS marketing increases its use/intention to use. Evidence was moderate for ENDS association with mental health and substance use, limited-suggestive for cardiovascular, and limited-not-conclusive for cancer, ear, ocular and oral diseases, and pregnancy outcomes.ConclusionsAs evidence is accumulating, ENDS communication can focus on high-level evidence on ENDS association with toxicity, nicotine addiction, respiratory disease, ENDS-specific harm (explosion, poisoning) and anti-ENDS industry sentiment. Direct comparison between the harm of CCs and ENDS should be avoided.PROSPERO registration numberCRD42021241630.

BackgroundAdoption of injury prevention exercise programmes (IPEPs) in team sports is contingent on behaviour change among coaches. The aim was to study motivation and goal-pursuit in IPEP use among coaches of amateur football players.MethodsA cross-sectional study using web-based questionnaires was administered to coaches in one Swedish regional football district. The study was carried out one season after dissemination of the IPEP Knee Control+. The questionnaire was based on the Health Action Process Approach and covered perceptions and beliefs about using Knee Control+. Questions were rated on 1–7 Likert scales.Results440 coaches participated (response rate 32%). Coaches were neutral about injury risks (median 4–5) and knowledge about preventing injuries (median 5) but had positive outcome expectancies of preventive training (median 6). Coaches who had used an IPEP perceived they had more knowledge about preventing injuries than non-users (median 5 vs 4, small effect size d=0.43). Coaches who used Knee Control+were positive about their practical ability to use it (median 6) and had high intention to prioritise continuous use (median 7). Highly adherent coaches to higher extent believed that specific training may prevent injuries and had plans for how to instruct the players and how to work around barriers compared with low adherent coaches.ConclusionCoaches need more knowledge and support on IPEP usage and how to structure training. Coaches who had adopted Knee Control+had high belief in their abilities but may need constructive plans on how to use the programme and to overcome barriers.

Pubertal timing varies considerably and is associated with later health outcomes. We performed multi-ancestry genetic analyses on ~800,000 women, identifying 1,080 signals for age at menarche. Collectively, these explained 11% of trait variance in an independent sample. Women at the top and bottom 1% of polygenic risk exhibited ~11 and ~14-fold higher risks of delayed and precocious puberty, respectively. We identified several genes harboring rare loss-of-function variants in ~200,000 women, including variants in ZNF483, which abolished the impact of polygenic risk. Variant-to-gene mapping approaches and mouse gonadotropin-releasing hormone neuron RNA sequencing implicated 665 genes, including an uncharacterized G-protein-coupled receptor, GPR83, which amplified the signaling of MC3R, a key nutritional sensor. Shared signals with menopause timing at genes involved in DNA damage response suggest that the ovarian reserve might signal centrally to trigger puberty. We also highlight body size-dependent and independent mechanisms that potentially link reproductive timing to later life disease.

In this paper, we promote and motivate research on user experience (UX) in the domain of rail, more specifically for the workers engaged in the daily operational parts of executing train traffic. UX aspects have often been overlooked in the design and use of technology within the workplace, particularly in safety-critical work domains. Here, we provide an overview of current UX research at work and outline a roadmap with seven facets for future research within the domain of operational train traffic that is in alignment with the need for further investigation into UX at work. We hope future research will contribute to a deeper understanding of how positive experience at work provides additional means of enhancing engagement and improving safety management in workplaces in general and for the work in operational train traffic specifically.

Purpose: This study aims to investigate the social and affective impacts of inviting residents of a socially divided, post-war city to “play tourist” for a day, exploring their own backyards with a new intentionality and perspective. Design/methodology/approach: This qualitative research within a transformative worldview uses a creative, place-based approach of role-playing based upon principles of participatory action research. Findings: While each tour was unique, participants’ insights reflected three common themes: shifts in observations and perceptions of place arising from the intentionality of the “tourist” lens, a sense of freedom created by the touristic research opportunity, and the varying abilities of tourism experiences to help build empathy or awareness in a post-conflict setting. Originality/value: The inventive research approach allows for a unique examination of local tourism-styled explorations, a subject of growing interest that has largely been overlooked in literature, while paying special attention to ways in which a history of conflict may manifest in contemporary urban tourism experiences.

Using non-hazardous industrial residues in mine waste remediation is beneficial not only for the mining industry where substantial amounts of the waste generated have potential to produce acid rock drainage and pollute the environment, but also the providing industry, minimizing the waste landfilled. In this study green liquor dregs (GLD), residue from 15 different paper mills were characterized to valorize it as a potential product as a cover material. In another part of the study, one of the GLDs and a local till were characterized to determine the optimal mixture of GLD amended till to be used in a field application at the closed Näsliden Mine in northern Sweden. The study concluded 10% GLD-amended till to be the optimal recipe and was successfully applied at the Näsliden mine waste dump. However, the great variability in the characteristics of GLD creates challenges if it is to be valorized as a product.

The deoxygenation of environmental pollutants CO2and NO2–to form value-added products is reported. CO2reduction with subsequent CO release and NO2–conversion to NO are achieved via the starting complex Fe(PPhPDI)Cl2(1). 1contains the redox-active pyridinediimine (PDI) ligand with a hemilabile phosphine located in the secondary coordination sphere. 1was reduced with SmI2under a CO2atmosphere to form the direduced monocarbonyl Fe(PPhPDI)(CO) (2). Subsequent CO release was achieved via oxidation of 2using the NOx–source, NO2–. The resulting [Fe(PPhPDI)(NO)]+(3) mononitrosyl iron complex (MNIC) is formed as the exclusive reduction product due to the hemilabile phosphine. 3was investigated computationally to be characterized as {FeNO}7, an unusual intermediate-spin Fe(III) coupled to triplet NO–and a singly reduced PDI ligand.

IntroductionThis study examines how current smokers using menthol cigarettes or flavoured cigars, and current users of flavoured e-cigarettes may respond to three hypothetical flavour-ban scenarios: (1) banning only menthol cigarettes and flavoured cigars; (2) also banning e-cigarettes with any non-tobacco flavours except menthol; and (3) also banning e-cigarettes with any non-tobacco flavours, including menthol.MethodsRecruited from mTurk, respondents were asked if they would quit all tobacco-nicotine use or continue or start using products that were still legally available. The patterns of responding to each ban scenario, for both flavoured smokers and users of non-tobacco flavoured e-cigarettes, were summarised. Multinomial logistic regressions were used to estimate associations between demographics, smoking or e-cigarette use status and reactions to a ban.ResultsA ban on menthol cigarettes and flavoured cigars would lead to 12%–20% of flavoured smokers trying to quit all tobacco use and 32%–52% switching to non-flavoured smoking, with the remaining switching to e-cigarettes or other products. Compared with a ban on only menthol cigarettes and flavoured cigars, also banning flavoured e-cigarettes would increase the likelihood of quitting all tobacco-nicotine use (OR=2.58) but also increase the likelihood of switching to non-flavoured smoking (OR=1.74).ConclusionsOur results indicate that a ban on menthol cigarettes and flavoured cigars would decrease smoking. However, it is unclear if adding a ban of menthol e-cigarettes would lead to additional benefits because without menthol e-cigarettes as an alternative, some smokers and e-cigarette users may switch to non-flavoured tobacco smoking, rather than quit all tobacco use.

Banning flavors in e-cigarettes and other tobacco products may decrease their use. To examine how current users of flavored e-cigarettes might react to a ban on flavored e-cigarettes when: (i) menthol flavor is banned together with other flavors, or (ii) this ban on e-cigarettes is combined with a ban on menthol cigarettes and flavored cigars. A national cross-sectional survey of 2,347 current users of flavored e-cigarettes was conducted in May 2022. For each hypothetical ban scenario, respondents reported if they would quit all tobacco product use, continue to use e-cigarettes with no flavor or flavors that were not banned, or switch to alternative tobacco products. Multinomial logistic regressions were used to estimate the associations between responses and ban scenarios, adjusting for tobacco use and demographic variables.If e-cigarettes with any flavors except menthol and tobacco were banned, the majority of current e-cigarette users would keep using e-cigarettes with no flavor or tobacco and menthol flavor. When menthol flavor was added to a ban, a greater proportion of respondents would quit all tobacco use; however, more would also switch to cigarettes or cigars. When menthol cigarettes and flavored cigars were added to a ban, those who used menthol flavor only would be less likely to switch to cigarettes and cigars.Among current e-cigarette users, the harm reduction (i.e., from quitting all use) from a ban on flavored e-cigarettes, particularly if menthol is also banned, may be outweighed by the harm increases (i.e., switching to cigarettes or cigars, or other products that are more harmful than using e-cigarettes). A concurrent ban on menthol cigarettes and flavored cigars would secure more certain net reductions to public health harms from e-cigarette use and smoking.For current flavored e-cigarette users, the harm reduction (i.e., from quitting all use) from a ban on flavored e-cigarettes, particularly if menthol is also banned, may be outweighed by the harm increases (i.e., switching to cigarettes or cigars, or other products that are more harmful than using e-cigarettes).Banning flavors in e-cigarettes and other tobacco products has the potential to decrease their use. We examined how current users of flavored e-cigarettes might react to several hypothetical ban scenarios. We found that if e-cigarettes with any added flavors except tobacco or menthol were banned, the majority of current e-cigarette users would keep using non-flavored e-cigarettes or those with flavors that were not banned. When menthol flavor was added to a ban, a greater proportion of respondents would quit all tobacco use, however, more would also switch to cigarettes or cigars. When menthol cigarettes and flavored cigars were added to a ban, those who used menthol-flavor e-cigarettes only would be less likely to switch to cigarettes and cigars. Our study indicated that among current e-cigarette users, the harm-reduction resulting from a ban on flavored e-cigarettes, particularly when menthol was banned (i.e., from users quitting all use), may be outweighed by the harm increases (i.e., switching to cigarettes or cigars, or other products that are more harmful than using e-cigarettes). Concurrently banning menthol cigarettes and flavored cigars would secure more certain net harm reductions.

The Shuttle has a hardware RAID controller and is capable of being configured with 4 TB, 6 TB, 8 TB and 12 TB drives, or with two 10 or 12 TB drives and two EV bays. Ultimately, choosing the right drive or drives comes down to understanding how the drive will fit into your workflow. Features In this guide, you'll find a list of the best storage drives on the market today, hand-picked by the Videomaker editors. In a case like this, the data may still be on the drives, but recovery might be difficult since many RAID controllers write data to drives differently. [Extracted from the article]

IntroductionTo understand the impact of e-cigarette devices, flavours, nicotine levels and prices on adult e-cigarette users’ choices among closed-system and open-system e-cigarettes, cigarettes and heated tobacco products (HTPs).MethodsOnline discrete choice experiments were conducted among adult (≥18 years) e-cigarette users (n=2642) in August 2020. Conditional logit regressions were used to assess the relative impact of product attributes and the interactions between product attributes and user characteristics, with stratified analyses to examine differences by smoking status and primarily used e-cigarette device and flavour.ResultsOn average, participants preferred non-tobacco and non-menthol flavours most, preferred open-system over closed-system e-cigarettes and preferred regular nicotine level over low nicotine level. However, the preference varied by demographics, smoking status and the primarily used e-cigarette device and flavour. The differences in preference among products/devices were larger than the difference among flavours or nicotine levels. Participants who primarily used closed-system e-cigarettes exhibited similar preferences for closed-system and open-system e-cigarettes, but those who primarily used open-system e-cigarettes preferred much more open-system over closed-system e-cigarettes. HTP was the least preferred product, much lower than cigarettes in general, but participants living in states where IQOS is being sold had similar preferences to cigarettes and HTPs.ConclusionsPeople are unlikely to switch to another product/device because of the restriction of flavour or nicotine level. If non-tobacco and non-menthol flavours were banned from open-system e-cigarettes, users may switch to menthol flavour e-cigarettes. Intervention strategies should be tailored to specific groups.

Previous studies showed a low-grade enterovirus infection in the pancreatic islets of patients with newly diagnosed type 1 diabetes (T1D). In the Diabetes Virus Detection (DiViD) Intervention, a phase 2, placebo-controlled, randomized, parallel group, double-blind trial, 96 children and adolescents (aged 6–15 years) with new-onset T1D received antiviral treatment with pleconaril and ribavirin (n= 47) or placebo (n= 49) for 6 months, with the aim of preserving β cell function. The primary endpoint was the mean stimulated C-peptide area under the curve (AUC) 12 months after the initiation of treatment (less than 3 weeks after diagnosis) using a mixed linear model. The model used longitudinal log-transformed serum C-peptide AUCs at baseline, at 3 months, 6 months and 1 year. The primary endpoint was met with the serum C-peptide AUC being higher in the pleconaril and ribavirin treatment group compared to the placebo group at 12 months (average marginal effect = 0.057 in the linear mixed model; 95% confidence interval = 0.004–0.11, P= 0.037). The treatment was well tolerated. The results show that antiviral treatment may preserve residual insulin production in children and adolescent with new-onset T1D. This provides a rationale for further evaluating antiviral strategies in the prevention and treatment of T1D. European Union Drug Regulating Authorities Clinical Trials identifier: 2015-003350-41.

BackgroundThe Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) framework can be used for evaluation of implementation initiatives in sports injury prevention. The aim was to evaluate the implementation of the injury prevention exercise programme Knee Control+among amateur clubs and coaches in one regional football district using all five dimensions of the RE-AIM framework.MethodsDissemination of Knee Control+during the 2021 season with information and webinars within one regional football district. This was followed by a cross-sectional study with questionnaires to club personnel and coaches after the season.ResultsThe reach of Knee Control+was fair to high, 83% of club personnel and 66% of coaches knew about the programme. 41% of club personnel and 51% of coaches had adopted it. Perceived programme effectiveness was high (6 on a 1–7 Likert scale) among coaches. Regarding implementation and maintenance, 27% of club personnel had informed coaches about Knee Control+and 57% planned to inform coaches. The coaches had implemented the programme mainly as recommended, but half used the programme once per week or less. Intention to maintain use of the programme was high (7 on a 1–7 Likert scale) among coaches.ConclusionThe reach of Knee Control+was fair to high, and adoption was fair in clubs, but there was a lack of policies for preventive training. Active strategies probably need to accompany dissemination of programme material. Reach, perceived effectiveness, adoption, implementation and planned maintenance were positive among coaches, but further studies are needed to analyse long-term maintenance.

BackgroundA growing number of states or jurisdictions in the USA have imposed excise taxes on electronic nicotine delivery systems (ENDS). However, there is no consensus on how best to tax ENDS.ObjectivesWe specifically compare the tax incidence or burden for ENDS and cigarettes and analyse how ENDS tax incidence is associated with the choices of tax bases and rates.MethodsWe calculate ENDS excise tax incidence as the percentage of retail prices for each state or jurisdiction. Next, we use ordinary least squares to evaluate how tax incidence is associated with the choices of tax bases (eg, a specific tax base vs a value or ad valorem tax base) and rates and how these associations are moderated by product types.ResultsENDS and cigarette tax incidence is similar at the state level. Nonetheless, when federal cigarette taxes are considered, the cigarette tax incidence is higher than the tax incidence on closed-system ENDS. The proportion of states that impose value taxes is higher for open systems (65.4%) than for closed systems (46.2%). A value tax base is associated with a 7 percentage point lower tax incidence compared with a specific tax base. Product type further moderates the association between tax base and incidence.ConclusionTax incidence can be used to measure the strength of ENDS tax policies and how they are compared with cigarette taxes. Policymakers who aim to prevent youth from using ENDS may consider a value tax base to raise the tax incidence of closed systems—the product type preferred by young people.

Evidence from literature, including the BRIDGES study, indicates that germline protein truncating variants (PTVs) in FANCMconfer moderately increased risk of ER-negative and triple-negative breast cancer (TNBC), especially for women with a family history of the disease. Association between FANCMmissense variants (MVs) and breast cancer risk has been postulated. In this study, we further used the BRIDGES study to test 689 FANCMMVs for association with breast cancer risk, overall and in ER-negative and TNBC subtypes, in 39,885 cases (7566 selected for family history) and 35,271 controls of European ancestry. Sixteen common MVs were tested individually; the remaining rare 673 MVs were tested by burden analyses considering their position and pathogenicity score. We also conducted a meta-analysis of our results and those from published studies. We did not find evidence for association for any of the 16 variants individually tested. The rare MVs were significantly associated with increased risk of ER-negative breast cancer by burden analysis comparing familial cases to controls (OR = 1.48; 95% CI 1.07–2.04; P= 0.017). Higher ORs were found for the subgroup of MVs located in functional domains or predicted to be pathogenic. The meta-analysis indicated that FANCMMVs overall are associated with breast cancer risk (OR = 1.22; 95% CI 1.08–1.38; P= 0.002). Our results support the definition from previous analyses of FANCMas a moderate-risk breast cancer gene and provide evidence that FANCMMVs could be low/moderate risk factors for ER-negative and TNBC subtypes. Further genetic and functional analyses are necessary to clarify better the increased risks due to FANCMMVs.

ObjectiveTo evaluate the preventive efficacy of an extended version of the Knee Controlinjury prevention exercise programme (IPEP) compared with an adductor strength programme and to a comparison group using a self-selected IPEP in amateur adolescent and adult male and female football players.MethodsTwo-armed cluster-randomised trial with an additional non-randomised arm. All 251 amateur teams (players 14–46 years) in one regional football district were approached. Teams meeting inclusion criteria were randomised to (1) extended Knee Controlor (2) an adductor strength programme. Teams already using an IPEP were allocated to a comparison group and received no new intervention. Players responded to weekly questionnaires about football exposures and injuries during a 7-month season.ResultsSeventeen teams in the extended Knee Control, 12 in the adductor and 17 in the comparison group participated, with 502 players. For the primary outcomes, no difference in injury incidence in three lower-limb injury locations combined (hamstring, knee and ankle) was seen between extended Knee Controland the adductor group, whereas extended Knee Controlhad 29% lower incidence than the comparison group (incidence rate ratio 0.71, 95% CI 0.52 to 0.98). No between-group differences in groin injury incidence were seen. The weekly injury prevalence rates in the three lower limb locations combined (hamstring, knee and ankle) were 17% lower (prevalence rate ratio (PRR) 0.83, 95% CI 0.69 to 1.00) and 26% lower (PRR 0.74, 95% CI 0.63 to 0.87) in extended Knee Controlcompared with the adductor and comparison groups, respectively.ConclusionNo difference in injury incidence was seen between the extended Knee Controland the adductor programme whereas extended Knee Controlreduced injury incidence by nearly one-third compared with a self-selected IPEP. Players in extended Knee Controlhad lower injury prevalence compared with an adductor or self-selected IPEP.Trial registration numberNCT04272047; Clinical trials.

BackgroundPolygenic risk score (PRS), calculated based on genome-wide association studies (GWASs), can improve breast cancer (BC) risk assessment. To date, most BC GWASs have been performed in individuals of European (EUR) ancestry, and the generalisation of EUR-based PRS to other populations is a major challenge. In this study, we examined the performance of EUR-based BC PRS models in Ashkenazi Jewish (AJ) women.MethodsWe generated PRSs based on data on EUR women from the Breast Cancer Association Consortium (BCAC). We tested the performance of the PRSs in a cohort of 2161 AJ women from Israel (1437 cases and 724 controls) from BCAC (BCAC cohort from Israel (BCAC-IL)). In addition, we tested the performance of these EUR-based BC PRSs, as well as the established 313-SNP EUR BC PRS, in an independent cohort of 181 AJ women from Hadassah Medical Center (HMC) in Israel.ResultsIn the BCAC-IL cohort, the highest OR per 1 SD was 1.56 (±0.09). The OR for AJ women at the top 10% of the PRS distribution compared with the middle quintile was 2.10 (±0.24). In the HMC cohort, the OR per 1 SD of the EUR-based PRS that performed best in the BCAC-IL cohort was 1.58±0.27. The OR per 1 SD of the commonly used 313-SNP BC PRS was 1.64 (±0.28).ConclusionsExtant EUR GWAS data can be used for generating PRSs that identify AJ women with markedly elevated risk of BC and therefore hold promise for improving BC risk assessment in AJ women.

Colorectal cancer (CRC) is a leading cause of mortality worldwide. We conducted a genome-wide association study meta-analysis of 100,204 CRC cases and 154,587 controls of European and east Asian ancestry, identifying 205 independent risk associations, of which 50 were unreported. We performed integrative genomic, transcriptomic and methylomic analyses across large bowel mucosa and other tissues. Transcriptome- and methylome-wide association studies revealed an additional 53 risk associations. We identified 155 high-confidence effector genes functionally linked to CRC risk, many of which had no previously established role in CRC. These have multiple different functions and specifically indicate that variation in normal colorectal homeostasis, proliferation, cell adhesion, migration, immunity and microbial interactions determines CRC risk. Crosstissue analyses indicated that over a third of effector genes most probably act outside the colonic mucosa. Our findings provide insights into colorectal oncogenesis and highlight potential targets across tissues for new CRC treatment and chemoprevention strategies.

Identification of unidentified remains involves a comparison of ante- and postmortem features using biological identifiers. Anthropological identifiers, referred to by International Criminal Police Organization (INTERPOL) as secondary identifiers, have often been judged less reliable than DNA, fingerprints and dental records (referred to as primary identifiers). However, anthropological identifiers have been proven as discriminatory as the primary sources in many instances, and play a decisive role in positive identification. To guarantee better use of anthropological identifiers, it is not only essential to develop standard protocols and statistical frameworks, but also to test different identification approaches in cases from daily practice. Evidence of skeletal antemortem trauma can be a valuable aid in the identification process, especially if the exact type of traumatic event causing the injury is identified. Here, we present a case in which the combination of anthropological analysis and imaging confirmed an interesting and unique sequence of antemortem traumatic events in incomplete skeletal remains. The remains were assumed to pertain to an individual who went missing several years earlier, and whose medical records revealed a unique history of trauma to the right femur. The individual had sustained a fracture due to a fall from a high height followed, 10 years after the primary trauma, by a gunshot wound to the same bone; both treated by intramedullary nail fixation. While the anthropological analysis matched the biological profile of the missing individual and identified a healed defect to the right femur compatible with a gunshot wound, the radiological examination indicated that the bone underwent three surgical procedures on different occasions. Radiological examination also identified a pre-existing healed fracture adjacent to the gunshot defect. In addition to presenting the identification process in this specific case, this article discusses the difficulties in antemortem trauma interpretation, importance of combining macroscopic and radiological analysis to aid the reconstruction of previous traumatic events and mechanisms of injury from healed fractures that can play important roles in forensic human identification.

This article from Videomaker provides a guide for building a custom PC for video editing. It highlights the best PC components currently on the market, including the best CPU, RAM, GPU, and system drive options. The article emphasizes the importance of considering factors such as performance, price, and compatibility when selecting these components. It also offers budget-friendly alternatives for each category. The article concludes by advising readers to build a system that meets their specific video editing needs without overspending on unnecessary features. [Extracted from the article]

This article provides a list of the best laptops for video editing in 2024. It highlights several options for different budgets and preferences. The Asus Vivobook Pro 15 OLED is recommended as the best budget laptop, offering a powerful processor and graphics at an affordable price. The MSI Creator M16 is suggested as the best portable laptop, with impressive processing power and a high-quality display. For Mac users on a budget, the Apple 14-inch MacBook Pro M2 is recommended, while the Apple 16-inch MacBook Pro M2 Max is suggested as the best Mac laptop overall. The HP ZBook Studio G9 is highlighted as the best performance laptop, and the MSI 15.6-inch Stealth 15 is recommended for editors who also enjoy gaming. The article also provides guidance on choosing the right laptop, including considerations such as operating system, screen size and resolution, battery life, connectivity, and portability. [Extracted from the article]

Features In this article, we'll highlight our picks for the best video editing laptops on the market today, then go over the main points a potential buyer will want to consider in choosing the right mobile workstation. Best portable laptop MSI Creator 15 Design specifically for creators, the MSI Creator 15 features a 2.3 GHz Intel Core i7-10875H eight-core processor, a 15.6" Full HD IPS Display and 512GB NVMe PCIe M.2 SSD. Best performance laptop HP Zbook Studio 15.6" G8 You would be hard-pressed to find a more powerful laptop than the HP Zbook Studio 15.6" G8 Mobile Workstation. [Extracted from the article]

ABSTRACTThis methodologically focused paper introduces construal level theory of psychological distance (CLT) as a useful framework for tourism and community researchers and planners. This paper compares how residents’ affective responses of satisfaction vary across envisioned scenarios pertaining to local tourism sites, presented with varying degrees of detail and geographic specificity. Two scenarios are tested across three sites of interest, comparing residents’ responses to the sites envisioned generally to the same sites envisioned with tourists visiting. To pinpoint endogenous factors influencing differences in responses, resident subgroups pertaining to neighborhood, work sector, and frequency encountering tourists are compared, reflecting the specific context of a re-emerging, post-war destination. This research suggests that CLT can be a valuable tool to help tourism planners understand the complexities of affective dimensions that may be present in destination communities and identify root causes of support or resistance for tourism development and projects.

ObjectivesPhysical inactivity and sedentary behaviour are associated with higher breast cancer risk in observational studies, but ascribing causality is difficult. Mendelian randomisation (MR) assesses causality by simulating randomised trial groups using genotype. We assessed whether lifelong physical activity or sedentary time, assessed using genotype, may be causally associated with breast cancer risk overall, pre/post-menopause, and by case-groups defined by tumour characteristics.MethodsWe performed two-sample inverse-variance-weighted MR using individual-level Breast Cancer Association Consortium case-control data from 130 957 European-ancestry women (69 838 invasive cases), and published UK Biobank data (n=91 105–377 234). Genetic instruments were single nucleotide polymorphisms (SNPs) associated in UK Biobank with wrist-worn accelerometer-measured overall physical activity (nsnps=5) or sedentary time (nsnps=6), or accelerometer-measured (nsnps=1) or self-reported (nsnps=5) vigorous physical activity.ResultsGreater genetically-predicted overall activity was associated with lower breast cancer overall risk (OR=0.59; 95% confidence interval (CI) 0.42 to 0.83 per-standard deviation (SD;~8 milligravities acceleration)) and for most case-groups. Genetically-predicted vigorous activity was associated with lower risk of pre/perimenopausal breast cancer (OR=0.62; 95% CI 0.45 to 0.87,≥3 vs. 0 self-reported days/week), with consistent estimates for most case-groups. Greater genetically-predicted sedentary time was associated with higher hormone-receptor-negative tumour risk (OR=1.77; 95% CI 1.07 to 2.92 per-SD (~7% time spent sedentary)), with elevated estimates for most case-groups. Results were robust to sensitivity analyses examining pleiotropy (including weighted-median-MR, MR-Egger).ConclusionOur study provides strong evidence that greater overall physical activity, greater vigorous activity, and lower sedentary time are likely to reduce breast cancer risk. More widespread adoption of active lifestyles may reduce the burden from the most common cancer in women.

Reproductive longevity is essential for fertility and influences healthy ageing in women1,2, but insights into its underlying biological mechanisms and treatments to preserve it are limited. Here we identify 290 genetic determinants of ovarian ageing, assessed using normal variation in age at natural menopause (ANM) in about 200,000 women of European ancestry. These common alleles were associated with clinical extremes of ANM; women in the top 1% of genetic susceptibility have an equivalent risk of premature ovarian insufficiency to those carrying monogenic FMR1premutations3. The identified loci implicate a broad range of DNA damage response (DDR) processes and include loss-of-function variants in key DDR-associated genes. Integration with experimental models demonstrates that these DDR processes act across the life-course to shape the ovarian reserve and its rate of depletion. Furthermore, we demonstrate that experimental manipulation of DDR pathways highlighted by human genetics increases fertility and extends reproductive life in mice. Causal inference analyses using the identified genetic variants indicate that extending reproductive life in women improves bone health and reduces risk of type 2 diabetes, but increases the risk of hormone-sensitive cancers. These findings provide insight into the mechanisms that govern ovarian ageing, when they act, and how they might be targeted by therapeutic approaches to extend fertility and prevent disease.

Background: Accumulating data suggest infectious agents are involved in Alzheimer’s disease (AD). The two primary aims of this trial were to assess safety and efficacy of an antiviral drug combination on AD progression.Objective: The trial evaluated whether Apovir, a combination of two antiviral agents, pleconaril (active on enteroviruses) and ribavirin (active on several viruses), could slow AD progression.Methods: Sixty-nine patients 60–85 years were treated with Apovir or placebo for 9 months and followed until 12 months after end of treatment. Cognitive tests, safety, biomarkers, drug plasma, and cerebrospinal fluid concentrations were assessed.Results: The tolerability of Apovir was compromised as demonstrated by the large drop-out rate and increased frequency and severity of adverse events. The primary endpoint, demonstrating a difference in change from baseline to 9 months between groups in ADAS-cog total score, was not met (p?=?0.1809). However, there were observations indicating potential effects on both ADAS-cog and CDR-SB but these effects need to be verified. Also, there was a decrease in cerebrospinal fluid amyloid-ß in Apovir at 9 months (p?=?0.0330) but no change in placebo.Conclusion: This was the first randomized, placebo controlled clinical trial exploring antiviral treatment on AD progression. The trial is considered inconclusive due to the large drop-out rate. New trials are needed to verify if the indications of effect observed can be confirmed and which component(s) in Apovir contributed to such effects. Pleconaril alone may be studied to improve the tolerability and to verify if enterovirus is involved in the disease process.

ObjectiveAn understanding of the etiologic heterogeneity of colorectal cancer (CRC) is critical for improving precision prevention, including individualized screening recommendations and the discovery of novel drug targets and repurposable drug candidates for chemoprevention. Known differences in molecular characteristics and environmental risk factors among tumors arising in different locations of the colorectum suggest partly distinct mechanisms of carcinogenesis. The extent to which the contribution of inherited genetic risk factors for CRC differs by anatomical subsite of the primary tumor has not been examined.DesignTo identify new anatomical subsite-specific risk loci, we performed genome-wide association study (GWAS) meta-analyses including data of 48 214 CRC cases and 64 159 controls of European ancestry. We characterised effect heterogeneity at CRC risk loci using multinomial modelling.ResultsWe identified 13 loci that reached genome-wide significance (p<5×10−8) and that were not reported by previous GWASs for overall CRC risk. Multiple lines of evidence support candidate genes at several of these loci. We detected substantial heterogeneity between anatomical subsites. Just over half (61) of 109 known and new risk variants showed no evidence for heterogeneity. In contrast, 22 variants showed association with distal CRC (including rectal cancer), but no evidence for association or an attenuated association with proximal CRC. For two loci, there was strong evidence for effects confined to proximal colon cancer.ConclusionGenetic architectures of proximal and distal CRC are partly distinct. Studies of risk factors and mechanisms of carcinogenesis, and precision prevention strategies should take into consideration the anatomical subsite of the tumour.