A biophysical limit for quorum sensing in biofilms.

Bacteria grow on surfaces in complex immobile communities known as biofilms, which are composed of cells embedded in an extracellular matrix. Within biofilms, bacteria often interact with members of their own species and cooperate or compete with members of other species via quorum sensing (QS). QS is a process by which microbes produce, secrete, and subsequently detect small molecules called autoinducers (AIs) to assess their local population density. We explore the competitive advantage of QS through agent-based simulations of a spatial model in which colony expansion via extracellular matrix production provides greater access to a limiting diffusible nutrient. We note a significant difference in results based on whether AI production is constitutive or limited by nutrient availability: If AI production is constitutive, simple QS-based matrix-production strategies can be far superior to any fixed strategy. However, if AI production is limited by nutrient availability, QS-based strategies fail to provide a significant advantage over fixed strategies. To explain this dichotomy, we derive a biophysical limit for the dynamic range of nutrient-limited AI concentrations in biofilms. This range is remarkably small (less than 10-fold) for the realistic case in which a growth-limiting diffusible nutrient is taken up within a narrow active growth layer. This biophysical limit implies that for QS to be most effective in biofilms AI production should be a protected function not directly tied to metabolism.

A molecular epidemiological study on Escherichia coli in young chicks with colibacillosis identified two possible outbreaks across farms.

Avian pathogenic Escherichia coli (APEC) is the cause of colibacillosis outbreaks in young poultry chicks, resulting in acute to peracute death. The high morbidity and mortality caused by colibacillosis results in poor animal welfare, reduced sustainability and economical loss worldwide. To advance the understanding of the molecular epidemiology, genomic relatedness and virulence traits of APEC, we performed systematic sampling from 45 confirmed colibacillosis broiler flocks with high first week mortality (FWM) during 2018-2021. From these flocks, 219 APEC isolates were whole genome sequenced (WGS) and bioinformatic analyses were performed. The bioinformatic analyses included sequence typing (ST), serotyping, detection of virulence-associated genes (VAGs) and phylogenetic analysis. Our results showed a high prevalence of ST23, ST429 and ST95 among APEC isolates from Norwegian broiler flocks, and identified ST23, ST429, ST117 and ST371 to cause disease more often alone, compared to ST95, ST69 and ST10. Phylogenetic analyses, together with associated metadata, identified two distinct outbreaks of colibacillosis across farms caused by ST429 and ST23 and gave insight into expected SNP distances within and between flocks identified with the same ST. Further, our results highlighted the need for combining two typing methods, such as serotyping and sequence typing, to better discriminate strains of APEC. Ultimately, systematic sampling of APEC from multiple birds in a flock, together with WGS as a diagnostic tool is important to identify the disease-causing APEC within a flock and to detect outbreaks of colibacillosis across farms.

Evaluating the Value for Money of Precision Medicine from Early Cycle to Market Access: A Comprehensive Review of Approaches and Challenges.

OBJECTIVES: This study aimed to perform a comprehensive review of modeling approaches and methodological and policy challenges in the economic evaluation (EE) of precision medicine (PM) across clinical stages. METHODS: First, a systematic review was performed to assess the approaches of EEs in the past 10 years. Next, a targeted review of methodological articles was conducted for methodological and policy challenges in performing EEs of PM. All findings were synthesized into a structured framework that focused on patient population, Intervention, Comparator, Outcome, Time, Equity and ethics, Adaptability and Modeling aspects, named the "PICOTEAM" framework. Finally, a stakeholder consultation was conducted to understand the major determinants of decision making in PM investment. RESULTS: In 39 methodological articles, we identified major challenges to the EE of PM. These challenges include that PM applications involve complex and evolving clinical decision space, that clinical evidence is sparse because of small subgroups and complex pathways in PM settings, a one-time PM application may have lifetime or intergenerational impacts but long-term evidence is often unavailable, and that equity and ethics concerns are exceptional. In 275 EEs of PM, current approaches did not sufficiently capture the value of PM compared with targeted therapies, nor did they differentiate Early EEs from Conventional EEs. Finally, policy makers perceived the budget impact, cost savings, and cost-effectiveness of PM as the most important determinants in decision making. CONCLUSIONS: There is an urgent need to modify existing guidelines or develop a new reference case that fits into the new healthcare paradigm of PM to guide decision making in research and development and market access.

Intentions and willingness to engage in risky driving behaviour among high school adolescents: evaluating the bstreetsmart road safety programme.

OBJECTIVE: To investigate the impact of a road safety programme on adolescents' willingness to engage in risky behaviour as probationary drivers, adjusted for covariates of interest. METHOD: The bstreetsmart is a road safety programme delivered to around 25 000 adolescent students annually in New South Wales. Using a smartphone-based app, student and teacher participation incentives, students were surveyed before and after programme attendance. Mixed-methods linear regression analysed pre/post-modified Behaviour of Young Novice Driver (BYNDS_M) scores. RESULTS: 2360 and 1260 students completed pre-event and post-event surveys, respectively. Post-event BYNDS_M scores were around three points lower than pre-event scores (-2.99, 95% CI -3.418 to -2.466), indicating reduced intention to engage in risky driving behaviours. Covariates associated with higher stated intentions of risky driving were exposure to risky driving as a passenger (1.21, 95% CI 0.622 to 2.011) and identifying as non-binary gender (2.48, 95% CI 1.879 to 4.085), adjusting for other predictors. CONCLUSIONS: Trauma-informed, reality-based injury prevention programmes can be effective in changing short-term stated intentions to engage in risky driving, among a pre-independent driving student population. The adolescent novice driver age group is historically challenging to engage, and injury prevention action must be multipronged to address the many factors influencing their behaviour.

Group Model Building on causes and interventions for falls in Singapore: insights from a systems thinking approach.

BACKGROUND: Falls in older adults are the result of a complex web of interacting causes, that further results in other physical, emotional, and psychological sequelae. A conceptual framework that represents the reciprocal dynamics of these causal factors can enable clinicians, researchers, and policymakers to clarify goals in falls intervention in older adults. METHODS: A Group Model Building (GMB) exercise was conducted with researchers and clinicians from academic units and public healthcare institutes in Singapore. The aim of the exercise was to produce a shared visual representation of the causal structure for falls and engage in discussions on how current and future falls intervention programmes can address falls in the older adults, especially in the Asian context. It was conducted in four steps: 1) Outlining and prioritising desirable patient outcomes, 2) Conceptual model building, 3) Identifying key intervention elements of effective falls intervention programmes, 4) Mapping of interventions to outcomes. This causal loop diagram (CLD) was then used to generate insights into the current understanding of falls causal relationships, current efforts in falls intervention in Singapore, and used to identify gaps in falls research that could be further advanced in future intervention studies. RESULTS: Four patient outcomes were identified by the group as key in falls intervention: 1) Falls, 2) Injurious falls, 3) Fear of falling, and 4) Restricted mobility and life space. A CLD of the reciprocal relationships between risk factors and these outcomes are represented in four sub-models: 1) Fear of falling, 2) Injuries associated with falls, 3) Caregiver overprotectiveness, 4) Post-traumatic stress disorder and psychological resilience. Through this GMB exercise, the group gained the following insights: (1) Psychological sequelae of falls is an important falls intervention outcome. (2) The effects of family overprotectiveness, psychological resilience, and PTSD in exacerbating the consequences of falls are not well understood. (3) There is a need to develop multi-component falls interventions to address the multitude of falls and falls related sequelae. CONCLUSION: This work illustrates the potential of GMB to promote shared understanding of complex healthcare problems and to provide a roadmap for the development of more effective preventive actions.

Development of a real-world database for asthma and COPD: The SingHealth-Duke-NUS-GSK COPD and Asthma Real-World Evidence (SDG-CARE) collaboration.

PURPOSE: The SingHealth-Duke-GlaxoSmithKline COPD and Asthma Real-world Evidence (SDG-CARE) collaboration was formed to accelerate the use of Singaporean real-world evidence in research and clinical care. A centerpiece of the collaboration was to develop a near real-time database from clinical and operational data sources to inform healthcare decision making and research studies on asthma and chronic obstructive pulmonary disease (COPD). METHODS: Our multidisciplinary team, including clinicians, epidemiologists, data scientists, medical informaticians and IT engineers, adopted the hybrid waterfall-agile project management methodology to develop the SingHealth COPD and Asthma Data Mart (SCDM). The SCDM was developed within the organizational data warehouse. It pulls and maps data from various information systems using extract, transform and load (ETL) pipelines. Robust user testing and data verification was also performed to ensure that the business requirements were met and that the ETL pipelines were valid. RESULTS: The SCDM includes 199 data elements relevant to asthma and COPD. Data verification was performed and found the SCDM to be reliable. As of December 31, 2019, the SCDM contained 36,407 unique patients with asthma and COPD across the spectrum from primary to tertiary care in our healthcare system. The database updates weekly to add new data of existing patients and to include new patients who fulfil the inclusion criteria. CONCLUSIONS: The SCDM was systematically developed and tested to support the use RWD for clinical and health services research in asthma and COPD. This can serve as a platform to provide research and operational insights to improve the care delivered to our patients.

Incentives for Uptake of and Adherence to Outpatient Stroke Rehabilitation Services: A 3-Arm Randomized Controlled Trial.

OBJECTIVE: To determine if rehabilitation uptake and adherence can be increased by providing coordinated transportation (increased convenience) and eliminating out-of-pocket costs (reduced expense). DESIGN: Three-arm randomized controlled trial. SETTING: Stroke units of 2 Singapore tertiary hospitals. PARTICIPANTS: Singaporeans or permanent residents 21 years or older who were diagnosed as having stroke and were discharged home with physician's recommendation to continue outpatient rehabilitation (N=266). INTERVENTIONS: A Transportation Incentives arm (T), which provides free transportation services, a Transportation & Sessions Incentives arm (T&S), offering free transportation and prescribed stroke rehabilitation sessions, and a control arm, Education (E), consisting of a stroke rehabilitation educational program. MAIN OUTCOME MEASURES: The primary study outcome was uptake of outpatient rehabilitation services (ORS) among patients poststroke and key predefined secondary outcomes being number of sessions attended and adherence to prescribed sessions. RESULTS: Uptake rate of ORS was 73.0% for E (confidence interval [CI], 63.8%-82.3%), 81.8% for T (CI, 73.8%-89.8%), and 84.3% for T&S (CI, 76.7%-91.8%). Differences of T and T&S vs E were not statistically significant (P=.22 and P=.10, respectively). However, average number of rehabilitation sessions attended were significantly higher in both intervention arms: 5.50±7.65 for T and 7.51±9.52 for T&S vs 3.26±4.22 for control arm (E) (T vs E: P=.017; T&S vs E: P<.001). Kaplan-Meier analysis indicated that persistence was higher for T&S compared with E (P=.029). CONCLUSIONS: This study has demonstrated a possibility in increasing the uptake of and persistence to stroke ORS with free transportation and sessions. Incentivizing survivors of stroke to take up ORS is a new strategy worthy of further exploration for future policy change in financing ORS or other long-term care services.

Developing integration among stakeholders in the primary care networks of Singapore: a qualitative study.

BACKGROUND: Integrating healthcare services across and between the different health system levels can be achieved in a few ways; however, examining the social side of integration is essential and challenging. This paper explores the concept of integration perceived by general practitioners (GPs) and primary care network (PCN) representatives from the regional health systems (RHS) in a GP-RHS PCN and their perceived partnership success. METHODS: In this study, we explored three GP-RHS PCNs in Singapore. We used a qualitative research design and, overall, performed 17 semi-structured in-depth interviews with GPs (n = 11) and PCN representatives (n = 6) from the RHS. All interviews were audiotaped and transcribed verbatim. We conducted thematic analysis to inductively identify themes from the data. Singer's conceptual model of integration types was used as guiding principles to derive relevant and salient themes for integration. RESULTS: GPs and the RHS perceived the concept of integration through a series of interrelated strategies. Within the normative dimension, a sense of urgency motivated GPs to integrate improvements into their general practice. Participants perceived teamwork and relational climate as appropriate enablers for achieving interpersonal integration in a primary care partnership. While developing a trusted relationship was a perceived success of this partnership across the network, developing camaraderie and gaining knowledge in chronic disease management through the components of functional integration was a perceived success at an individual general practice level. The data also revealed some operational challenges within the structural dimension and some inabilities of the PCN to achieve complete process integration. CONCLUSIONS: Our study points to multi-faceted integration, comprising various forms that need to be manifested at all levels of care to achieve coordinated, seamless, and comprehensive care for patients suffering from chronic conditions. The present iteration of the PCN has been shown to offer integration at a level that warrants praise but still requires structural and process integration improvement.

Population Segmentation Based on Healthcare Needs: Validation of a Brief Clinician-Administered Tool.

BACKGROUND: As populations age with increasingly complex chronic conditions, segmenting populations into clinically meaningful categories of healthcare and related service needs can provide healthcare planners with crucial information to optimally meet needs. However, while conventional approaches typically involve electronic medical records (EMRs), such records do not always capture information reliably or accurately. OBJECTIVE: We describe the inter-rater reliability and predictive validity of a clinician-administered tool, the Simple Segmentation Tool (SST) for categorizing older individuals into one of six Global Impression (GI) segments and eight complicating factors (CFs) indicative of healthcare and related social needs. DESIGN: Observational study ( ClinicalTrials.gov , number NCT02663037). PARTICIPANTS: Patients aged 55 years and above. MAIN MEASURES: Emergency department (ED) subjects (between May and June 2016) had baseline SST assessment by two physicians and a nurse concurrently seeing the same individual. General medical (GM) ward subjects (February 2017) had a SST assessment by their principal physician. Adverse events (ED visits, hospitalizations, and mortality over 90 days from baseline) were determined by a blinded reviewer. Inter-rater reliability was measured using Cohen's kappa. Predictive validity was evaluated using Cox hazard ratios based on time to first adverse event. KEY RESULTS: Cohen's kappa between physician-physician, service physician-nurse, and physician-nurse pairs for GI were 0.60, 0.71, and 0.68, respectively. Cox analyses demonstrated significant predictive validity of GI and CFs for adverse outcomes. CONCLUSIONS: With modest training, clinicians can complete a brief instrument to segment their patient into clinically meaningful categories of healthcare and related service needs. This approach can complement and overcome current limitations of EMR-based instruments, particularly with respect to whole-patient care. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02663037.

Long-term quality of life, sexual health and gastrointestinal function following colorectal cancer resection in an Asian cohort.

AIM: As populations age and cancer management improves, long-term survivorship and quality-of-life (QOL) outcomes are becoming equally important as oncological results. Data from Asian populations are scarce. We aimed to evaluate the sexual health, gastrointestinal function and QOL amongst colorectal cancer survivors in a tertiary referral centre in Singapore. METHOD: Adults who had undergone elective curative surgery for non-metastatic colorectal cancer at least 2 years prior were included. Exclusion criteria were cognitive disease, serious postoperative complications or recurrent cancer. Participants were invited to complete the European Organization for Research and Treatment of Cancer Quality of Life Questionnaires EORTC-QLQ-C30 and QLQ-CR29. Using multiple bivariate analysis, r scores were used to examine relationship trends between QOL domains and survivor sociodemographic and disease-specific characteristics. RESULTS: From February 2017 to July 2019, 400 responses were recorded. Median age and follow-up duration were 64 years (range 32-90) and 78 months (interquartile range 49-113) respectively. Patients who had Stage III cancer had better overall QOL scores compared to Stage I/II. Rectal (vs. colon) cancer negatively influenced sexual health and gastrointestinal function, but did not appear to affect overall QOL. Amongst our cohort, 57% (n = 129) of men and 43% (n = 75) of women were sexually active. Markers of socioeconomic status, including employment, education and housing type, were found to significantly impact perception of various aspects of QOL. CONCLUSION: Knowledge of factors which influence well-being can identify individuals who may benefit from tailored management strategies. Regular patient-doctor contact may play a role in building and maintaining positive perspectives of cancer survivors. Normative data should be obtained from local populations to facilitate future comparative research.

The incidence of necrotic enteritis in turkeys is associated with farm, season and faecal Eimeria oocyst counts.

BACKGROUND: Specific studies on the epidemiology of necrotic enteritis in turkeys are absent in the literature. Necrotic enteritis is common in turkeys and a leading cause of use of therapeutic antibiotics. This study describes the incidence of necrotic enteritis in turkey farms, and the association between incidence and bird age, season, faecal oocyst counts, grow-out size and feed mill. RESULTS: Necrotic enteritis was diagnosed post mortem in 20.2 % of 545 grow-outs of commercial female and male B.U.T. 10 turkeys started during the years 2010-2016. 80 % of all cases occurred at four to seven weeks of age. Median (minimum-maximum) age at disease detection was 37 (18-115) days. Turkey age at detection was influenced by season, and varied from 33 days among grow-outs hatched in February to 42 days among those hatched in July-August. The incidence also varied with season, showing peak occurrence among grow-outs hatched during February-March and the lowest incidence in turkeys hatched in July-August. 59 % of all cases were detected in 25 % of the farms. The incidence per farm varied from below 4 to 59 %. A multilevel mixed-effects logistic regression model indicated clear impacts of farm and season on incidence, and border-line impacts of grow-out size and feed mill. Grow-outs diagnosed with necrotic enteritis had higher counts of faecal Eimeria oocysts than grow-outs without a diagnosis. This difference was particularly clear during the high-risk period at five to seven weeks of age. Necrotic enteritis was the cause of treatment with therapeutic antibiotics in 88.2 % of all cases of treatment. CONCLUSIONS: Our data indicate that necrotic enteritis incidence in turkeys can be substantially influenced by risk factors at farm level. The incidence showed two seasonal peaks; a moderate peak in turkeys hatched in October/November and a marked peak in turkeys hatched during February/March. Mitigation measures at the farm may therefore be of particular importance during these months in farms located in the Northern temperate zone. Measures which effectively reduce counts of faecal Eimeria oocyst are likely to be among the more promising actions to take both at the farm and at population level.

Coronavirus disease 2019 (COVID-19): an evidence map of medical literature.

BACKGROUND: Since the beginning of the COVID-19 outbreak in December 2019, a substantial body of COVID-19 medical literature has been generated. As of June 2020, gaps and longitudinal trends in the COVID-19 medical literature remain unidentified, despite potential benefits for research prioritisation and policy setting in both the COVID-19 pandemic and future large-scale public health crises. METHODS: In this paper, we searched PubMed and Embase for medical literature on COVID-19 between 1 January and 24 March 2020. We characterised the growth of the early COVID-19 medical literature using evidence maps and bibliometric analyses to elicit cross-sectional and longitudinal trends and systematically identify gaps. RESULTS: The early COVID-19 medical literature originated primarily from Asia and focused mainly on clinical features and diagnosis of the disease. Many areas of potential research remain underexplored, such as mental health, the use of novel technologies and artificial intelligence, pathophysiology of COVID-19 within different body systems, and indirect effects of COVID-19 on the care of non-COVID-19 patients. Few articles involved research collaboration at the international level (24.7%). The median submission-to-publication duration was 8 days (interquartile range: 4-16). CONCLUSIONS: Although in its early phase, COVID-19 research has generated a large volume of publications. However, there are still knowledge gaps yet to be filled and areas for improvement for the global research community. Our analysis of early COVID-19 research may be valuable in informing research prioritisation and policy planning both in the current COVID-19 pandemic and similar global health crises.

Developing an experimental necrotic enteritis model in turkeys - the impact of Clostridium perfringens, Eimeria meleagrimitis and host age on frequency of severe intestinal lesions.

BACKGROUND: Necrotic enteritis is a significant problem to the poultry industry globally and, in Norway up to 30% of Norwegian turkey grow-outs can be affected. However, despite an awareness that differences exist between necrotic enteritis in chickens and turkeys, little information exists concerning the pathogenesis, immunity, microbiota or experimental reproduction of necrotic enteritis in turkeys. In particular, it is important to determine the appearance of the gross lesions, the age dependency of the disease and the role of netB toxin of Clostridium perfringens. To this end, we report our findings in developing an in vivo experimental model of necrotic enteritis in turkeys. RESULTS: A four tier (0-3) scoring system with clearly defined degrees of severity of macroscopic intestinal lesions was developed, based on 2312 photographic images of opened intestines from 810 B.U.T. 10 or B.U.T. Premium turkeys examined in nine experiments. Loss of macroscopically recognizable villi in the anterior small intestine was established as the defining lesion qualifying for a score 3 (severe intestinal lesions). The developed scoring system was used to identify important factors in promoting high frequencies of turkeys with severe lesions: a combined Eimeria meleagrimitis and Clostridium perfringens challenge, challenge at five rather than 3 weeks of age, the use of an Eimeria meleagrimitis dose level of at least 5000 oocysts per bird and finally, examination of the intestines of 5-week-old turkeys at 125 to 145 h after Eimeria meleagrimitis inoculation. Numbers of oocysts excreted were not influenced by Clostridium perfringens inoculation or turkey age. Among three different lesion score outcomes tested, frequency of severe lesions proved superior in discriminating between impact of four combinations of Clostridium perfringens inoculation and turkey age at challenge. CONCLUSIONS: This study provides details for the successful establishment of an in vivo model of necrotic enteritis in turkeys.

Do healthcare needs-based population segments predict outcomes among the elderly? Findings from a prospective cohort study in an urbanized low-income community.

BACKGROUND: A rapidly ageing population with increasing prevalence of chronic disease presents policymakers the urgent task of tailoring healthcare services to optimally meet changing needs. While healthcare needs-based segmentation is a promising approach to efficiently assessing and responding to healthcare needs at the population level, it is not clear how available schemes perform in the context of community-based surveys administered by non-medically trained personnel. The aim of this prospective cohort, community setting study is to evaluate 4 segmentation schemes in terms of practicality and predictive validity for future health outcomes and service utilization. METHODS: A cohort was identified from a cross-sectional health and social characteristics survey of Singapore public rental housing residents aged 60 years and above. Baseline survey data was used to assign individuals into segments as defined by 4 predefined population segmentation schemes developed in Singapore, Delaware, Lombardy and North-West London. From electronic data records, mortality, hospital admissions, emergency department visits, and specialist outpatient clinic visits were assessed for 180 days after baseline segment assignment and compared to segment membership for each segmentation scheme. RESULTS: Of 1324 residents contacted, 928 agreed to participate in the survey (70% response). All subjects could be assigned an exclusive segment for each segmentation scheme. Individuals in more severe segments tended to have lower quality of life as assessed by the EQ-5D Index for health utility. All population segmentation schemes were observed to exhibit an ability to differentiate different levels of mortality and healthcare utilization. CONCLUSIONS: It is practical to assign individuals to healthcare needs-based population segments through community surveys by non-medically trained personnel. The resulting segments for all 4 schemes evaluated in this way have an ability to predict health outcomes and utilization over the medium term (180 days), with significant overlap for some segments. Healthcare needs-based segmentation schemes which are designed to guide action hold particular promise for promoting efficient allocation of services to meet the needs of salient population groups. Further evaluation is needed to determine if these schemes also predict responsiveness to interventions to meet needs implied by segment membership.

Ultrastructure and cytochemistry of intrauterine embryonic and larval stages of Ityogonimus lorum (Digenea: Brachylaimidae) involving transitory development of ciliated miracidia.

Results of the present study provide ultrastructural evidence that miracidial morphogenesis is fully completed within the intrauterine eggs while in the most posterior uterine regions of Ityogonimus lorum, a digenean parasite of an Iberian mole, Talpa occidentalis (Eulipotyphla, Talpidae). Using transmission electron microscopy (TEM), the ultrastructural characteristics of diverse cell types and their organelles of these developing embryos and fully formed miracidia within the eggshell were examined. The eggshell and embryonic envelopes are similar to those described previously by many authors for other digeneans. However, the developing miracidia are unique among previously described digeneans in possessing transitory cilia during larvigenesis, but completely lacking cilia in fully formed miracidium larvae. The evidence for completion of miracidial maturation in intrauterine eggs is based on the presence of the following structures: (1) transitional stage of ciliated differentiating miracidial epithelium; (2) apical and lateral glands, characteristic for digenean miracidia; and (3) fully developed germinative cells grouped together in the germinative sac localized in the posterior region of the miracidium. The protonephridial system with its characteristic flame cells and the nervous system with diverse types of neurons and nerve centers, which are characteristic for other digenean species reported until now, are absent from all these developmental stages of I. lorum. Based on these observations, we hypothesize that the life cycle of I. lorum is entirely terrestrial, involving passive transmission by ingestion of eggs containing unciliated miracidia to the first intermediate host.

Associations between superoxide dismutase, malondialdehyde and all-cause mortality in older adults: a community-based cohort study.

BACKGROUND: Oxidative stress is an important theory of aging but population-based evidence has been lacking. This study aimed to evaluate the associations between biomarkers of oxidative stress, including plasma superoxide dismutase (SOD) activity and malondialdehyde (MDA), with all-cause mortality in older adults. METHODS: This is a community-based cohort study of 2224 participants (women:1227, median age: 86 years). We included individuals aged 65 or above and with plasma SOD activity and/or MDA tests at baseline. We evaluated the hazard ratios (HRs) and 95% confidence intervals (CIs) by multivariable Cox models. RESULTS: We documented 858 deaths during six years of follow-up. There was a significant interaction effect of sex with the association between SOD activity and mortality (P < 0.001). Compared with the lowest quintile, the risk of all-cause mortality was inversely associated with increasing quintiles of plasma SOD activity in women(P-trend< 0.001), with adjusted HRs for the second through fifth quintiles of 0.73 (95% CI 0.53-1.02), 0.52(95% CI 0.38-0.72), 0.53(95% CI 0.39-0.73), and 0.48(95% CI 0.35-0.66). There were no significant associations between SOD activity and mortality in men (P-trend = 0.64), and between MDA and mortality in all participants (P-trend = 0.79). CONCLUSIONS: Increased activity of SOD was independently associated with lower all-cause mortality in older women but not in men. This epidemiological study lent support for the free radical/oxidative stress theory of aging.

Do geographically isolated wetlands influence landscape functions?

Geographically isolated wetlands (GIWs), those surrounded by uplands, exchange materials, energy, and organisms with other elements in hydrological and habitat networks, contributing to landscape functions, such as flow generation, nutrient and sediment retention, and biodiversity support. GIWs constitute most of the wetlands in many North American landscapes, provide a disproportionately large fraction of wetland edges where many functions are enhanced, and form complexes with other water bodies to create spatial and temporal heterogeneity in the timing, flow paths, and magnitude of network connectivity. These attributes signal a critical role for GIWs in sustaining a portfolio of landscape functions, but legal protections remain weak despite preferential loss from many landscapes. GIWs lack persistent surface water connections, but this condition does not imply the absence of hydrological, biogeochemical, and biological exchanges with nearby and downstream waters. Although hydrological and biogeochemical connectivity is often episodic or slow (e.g., via groundwater), hydrologic continuity and limited evaporative solute enrichment suggest both flow generation and solute and sediment retention. Similarly, whereas biological connectivity usually requires overland dispersal, numerous organisms, including many rare or threatened species, use both GIWs and downstream waters at different times or life stages, suggesting that GIWs are critical elements of landscape habitat mosaics. Indeed, weaker hydrologic connectivity with downstream waters and constrained biological connectivity with other landscape elements are precisely what enhances some GIW functions and enables others. Based on analysis of wetland geography and synthesis of wetland functions, we argue that sustaining landscape functions requires conserving the entire continuum of wetland connectivity, including GIWs.

Can acute clinical outcomes predict health-related quality of life after stroke: a one-year prospective study of stroke survivors.

BACKGROUND: Health-related quality of life (HRQoL) is a key metric to understand the impact of stroke from patients' perspective. Yet HRQoL is not readily measured in clinical practice. This study aims to investigate the extent to which clinical outcomes during admission predict HRQoL at 3 months and 1 year post-stroke. METHODS: Stroke patients admitted to five tertiary hospitals in Singapore were assessed with Shah-modified Barthel Index (Shah-mBI), National Institute of Health Stroke Scale (NIHSS), Modified Rankin Scale (mRS), Mini-Mental State Examination (MMSE), and Frontal Assessment Battery (FAB) before discharge, and the EQ-5D questionnaire at 3 months and 12 months post-stroke. Association of clinical measures with the EQ index at both time points was examined using multiple linear regression models. Forward stepwise selection was applied and consistently significant clinical measures were analyzed for their association with individual dimensions of EQ-5D in multiple logistic regressions. RESULTS: All five clinical measures at baseline were significant predictors of the EQ index at 3 months and 12 months, except that MMSE was not significantly associated with the EQ index at 12 months. NIHSS (3-month standardized ß = - 0.111; 12-month standardized ß = - 0.109) and mRS (3-month standardized ß = - 0.122; 12-month standardized ß = - 0.080) were shown to have a larger effect size than other measures. The contribution of NIHSS and mRS as significant predictors of HRQoL was mostly explained by their association with the mobility, self-care, and usual activities dimensions of EQ-5D. CONCLUSIONS: HRQoL at 3 months and 12 months post-stroke can be predicted by clinical outcomes in the acute phase. NIHSS and mRS are better predictors than BI, MMSE, and FAB.

The comparative effectiveness of quadratus lumborum blocks and paravertebral blocks in radical cystectomy patients.

INTRODUCTION: Multimodal analgesia is an effective way to control pain and limit opioid use after surgery. The quadratus lumborum block and paravertebral block are two regional anesthesia techniques that leverage multimodal analgesia to improve postoperative pain control. We sought to compare the efficacy of these blocks for pain management following radical cystectomy. MATERIALS AND METHODS: We performed a retrospective review of radical cystectomy patients who received bilateral continuous paravertebral blocks (n = 125) or bilateral single shot quadratus lumborum blocks (n = 50) between 2014-2016. The primary outcome was postoperative opiate consumption on day 0. Secondary outcomes included self-reported pain scores and hospital length of stay. RESULTS: Quadratus lumborum block patients had similar opioid use on postoperative day 0 compared with paravertebral block patients (29 mg versus 30 mg, p = 0.90). Pain scores on postoperative day 0 were similar between quadratus lumborum block and paravertebral block groups (4.0 versus 3.8, p = 0.72); however, the paravertebral block group had lower pain scores on days 1-3 compared with the quadratus lumborum block group (all p < 0.05). Hospital length of stay was similar between groups (6.6 days versus 6.2 days, p = 0.41). CONCLUSIONS: There were no differences in opioid consumption among patients receiving bilateral single shot quadratus lumborum blocks and bilateral continuous paravertebral blocks after radical cystectomy. These data suggest that the quadratus lumborum block is a viable alternative for delivering multimodal analgesia in cystectomy patients.

Established Microbial Colonies Can Survive Type VI Secretion Assault.

Type VI secretion (T6S) is a cell-to-cell injection system that can be used as a microbial weapon. T6S kills vulnerable cells, and is present in close to 25% of sequenced Gram-negative bacteria. To examine the ecological role of T6S among bacteria, we competed self-immune T6S+ cells and T6S-sensitive cells in simulated range expansions. As killing takes place only at the interface between sensitive and T6S+ strains, while growth takes place everywhere, sufficiently large domains of sensitive cells can achieve net growth in the face of attack. Indeed T6S-sensitive cells can often outgrow their T6S+ competitors. We validated these findings through in vivo competition experiments between T6S+ Vibrio cholerae and T6S-sensitive Escherichia coli. We found that E. coli can survive and even dominate so long as they have an adequate opportunity to form microcolonies at the outset of the competition. Finally, in simulated competitions between two equivalent and mutually sensitive T6S+ strains, the more numerous strain has an advantage that increases with the T6S attack rate. We conclude that sufficiently large domains of T6S-sensitive individuals can survive attack and potentially outcompete self-immune T6S+ bacteria.