Functional Optimization in Complex Excitable Networks

We study the effect of varying wiring in excitable random networks in which connection weights change with activity to mold local resistance or facilitation due to fatigue. Dynamic attractors, corresponding to patterns of activity, are then easily destabilized according to three main modes, including one in which the activity shows chaotic hopping among the patterns. We describe phase transitions to this regime, and show a monotonous dependence of critical parameters on the heterogeneity of the wiring distribution. Such correlation between topology and functionality implies, in particular, that tasks which require unstable behavior --such as pattern recognition, family discrimination and categorization-- can be most efficiently performed on highly heterogeneous networks. It also follows a possible explanation for the abundance in nature of scale--free network topologies.Comment: 7 pages, 3 figure

Geospatial modelling of the prevalence and changing distribution of frailty in Australia – 2011 to 2027

Background and objectives: Detailed information about the current and future geographic distribution of Australia's frail population provides critical evidence to inform policy, resource allocation and planning initiatives that aim to treat and reverse frailty. Frailty is associated with poor health outcomes, including disability and death. It is also characterised by increased health care usage and costs. Understanding the distribution and growth of frailty is important for planning and budgeting service provision and health interventions aimed to support the needs of Australia's growing ageing population. The objective of this research is to provide baseline mapping and area level population estimates of Australia's current and future frail and pre-frail populations. Research design and methods: Geospatial modelling was applied to national frailty prevalence rates to provide estimates of the size, distribution and potential growth of Australia's frail and pre-frail population. Results: It is estimated that in 2016 approximately 415,769 people living in Australia aged 65 years or more are frail and almost 1.7 million people are pre-frail. In future years, as the population ages, these figures will increase rapidly, reaching 609,306 frail and 2,248,977 pre-frail by 2027, if prevalence continues at current levels. The geographic distribution of this projected growth is not uniform and while the largest frail populations will continue to be located in the major cities, the fastest growth will be in the outer metropolitan, regional and remote areas. Discussion and implications: The projected growth of frail populations in outer metropolitan, regional and remote areas may be reduced by targeting health interventions in these areas and improving access to support services. Frailty is a dynamic condition that is amenable to intervention. Reducing frailty will lead to benefits in wellbeing for older Australians in addition to reductions in health care costs.D. Taylor, H. Barrie, J. Lange, M.Q.Thompson, O.Theou, R.Visvanatha

An intra-COVID-19 assessment of hand hygiene facility, policy and staff compliance in two hospitals in Sierra Leone: is there a difference between regional and capital city hospitals?

Although hand hygiene (HH) is the most effective intervention to reduce the spread of infections, there are limited data on HH facilities, policy, and compliance in sub-Saharan Africa. This cross-sectional study is aimed at assessing HH using the WHO HH self-assessment framework, HH technical reference manual, and a modified infection control self-assessment tool in two hospitals in Sierra Leone. Only 10% and 9% of regional and capital city hospitals had running tap water, respectively. Veronica buckets were the resources for HH in 89% of units in the regional hospital and 92% of units in capital city hospital. Constant supply of soap and alcohol-based hand rub was available in 82% and 68%; and 74% and 79% of units in the capital city and regional hospitals, respectively. Only 10% of the units in both hospitals had hand-drying facilities and functional sinks. Overall HH compliance for the two hospitals was 18.6% and was higher in the regional (20.8%) than the capital city (17.0%) hospitals. The HH levels for the capital city and regional hospitals were 277.5 and 262.5 respectively. Despite the COVID-19 pandemic, there are still challenges with HH compliance in Sierra Leone. It is, therefore, necessary to strengthen the HH multi-modal strategy

Acetyl-CoA synthetase 2 promotes acetate utilization and maintains cancer cell growth under metabolic stress

A functional genomics study revealed that the activity of acetyl-CoA synthetase 2 (ACSS2) contributes to cancer cell growth under low-oxygen and lipid-depleted conditions. Comparative metabolomics and lipidomics demonstrated that acetate is used as a nutritional source by cancer cells in an ACSS2-dependent manner, and supplied a significant fraction of the carbon within the fatty acid and phospholipid pools. ACSS2 expression is upregulated under metabolically stressed conditions and ACSS2 silencing reduced the growth of tumor xenografts. ACSS2 exhibits copy-number gain in human breast tumors, and ACSS2 expression correlates with disease progression. These results signify a critical role for acetate consumption in the production of lipid biomass within the harsh tumor microenvironment

Incidence and risk factors of surgical site infections and related antibiotic resistance in Freetown, Sierra Leone: a prospective cohort study

BACKGROUND: There is limited information on surgical site infections (SSI) and the related antibiotic resistance needed to guide their management and prevention in Sierra Leone. In this study, we aimed to establish the incidence and risk factors of SSI and the related antibiotic resistance among adults attending a tertiary hospital, and a secondary health facility in Freetown, Sierra Leone. METHODS: This is a prospective cohort study designed to collect data from adult (18 years or older) patients who attended elective and emergency surgeries at two hospitals in Freetown between February and July, 2021. Data analysis was done using STATA version 16. RESULTS: Of 338 patients, 245 (72.5%) and 93 (27.5%) had their surgeries at the tertiary and secondary hospitals, respectively. Many were males 192 (56.8%), less than 35 years 164 (48.5%), and 39 (11.5%) developed an SSI. Of the 39 patients who acquired an SSI, 7 (17.9%) and 32 (82.1%) had their surgeries at the secondary and tertiary hospitals, respectively. The incidence of SSI is higher in contaminated 17 (43.6%) than in clean-contaminated 12 (30.8%) and clean 10 (25.6%) wounds. Wound swabs were collected in 29 (74.4%) patients, of which 18 (62.1%) had bacterial growth. In total, 49 isolates of 14 different bacteria including gram-negative 41 (83.7%) and gram-positive 8 (16.3%) isolates were identified. Of these, 32 (65.3%) were Enterobacteriaceae, 9 (18.4%) were Non-fermenting gram-negative bacilli and 10 (12.2%) were Enterococci. The most common isolates were Escherichia coli (12, 24.5%), Klebsiella pneumoniae (10, 20.4%), Acinetobacter baumannii (5, 10.2%), Klebsiella oxytoca (4, 8.2%) and Enterococcus faecalis (4, 8.2%). The Enterobacteriaceae were either resistance to carbapenems (4, 8.2%) or were extended-spectrum beta-lactamase (ESBL) producing organisms (29, 59.2%). Male sex [p = 0.031], an ASA score >/= 2 [p = 0.020), administration of general anaesthesia [p = 0.018] and elevated fasting glucose [p = 0.033] were predictive of SSI. CONCLUSION: The incidence of SSI in this study is comparable to other low- and middle-income countries, but a substantial proportion of these postoperative wounds have an ESBL-producing Enterobacteriaceae. Therefore, routine surveillance of SSI and related antibiotic resistance is required in resource-limited settings

Improved outcomes for hepatic trauma in England and Wales over a decade of trauma and hepatobiliary surgery centralisation

Background: Over the last decade trauma services have undergone a reconfiguration in England and Wales. The objective is to describe the epidemiology, management and outcomes for liver trauma over this period and examine factors predicting survival. Methods: Patients sustaining hepatic trauma were identified using the Trauma Audit and Research Network database. Demographics, management and outcomes were assessed between January 2005 and December 2014 and analysed over five, 2-year study periods. Independent predictor variables for the outcome of liver trauma were analysed using multiple logistic regression. Results: 4368 Patients sustained hepatic trauma (with known outcome) between January 2005 and December 2014. Median age was 34 years (interquartile range 23–49). 81% were due to blunt and 19% to penetrating trauma. Road traffic collisions were the main mechanism of injury (58.2%). 241 patients (5.5%) underwent liver-specific surgery. The overall 30-day mortality rate was 16.4%. Improvements were seen in early consultant input, frequency and timing of computed tomography (CT) scanning, use of tranexamic acid and 30-day mortality over the five time periods. Being treated in a unit with an on-site HPB service increased the odds of survival (odds ratio 3.5, 95% confidence intervals 2.7–4.5). Conclusions: Our study has shown that being treated in a unit with an on-site HPB service increased the odds of survival. Further evaluation of the benefits of trauma and HPB surgery centralisation is warranted

MR thermometry characterization of a hyperthermia ultrasound array designed using the k-space computational method

BACKGROUND: Ultrasound induced hyperthermia is a useful adjuvant to radiation therapy in the treatment of prostate cancer. A uniform thermal dose (43°C for 30 minutes) is required within the targeted cancerous volume for effective therapy. This requires specific ultrasound phased array design and appropriate thermometry method. Inhomogeneous, acoustical, three-dimensional (3D) prostate models and economical computational methods provide necessary tools to predict the appropriate shape of hyperthermia phased arrays for better focusing. This research utilizes the k-space computational method and a 3D human prostate model to design an intracavitary ultrasound probe for hyperthermia treatment of prostate cancer. Evaluation of the probe includes ex vivo and in vivo controlled hyperthermia experiments using the noninvasive magnetic resonance imaging (MRI) thermometry. METHODS: A 3D acoustical prostate model was created using photographic data from the Visible Human Project(®). The k-space computational method was used on this coarse grid and inhomogeneous tissue model to simulate the steady state pressure wavefield of the designed phased array using the linear acoustic wave equation. To ensure the uniformity and spread of the pressure in the length of the array, and the focusing capability in the width of the array, the equally-sized elements of the 4 × 20 elements phased array were 1 × 14 mm. A probe was constructed according to the design in simulation using lead zerconate titanate (PZT-8) ceramic and a Delrin(® )plastic housing. Noninvasive MRI thermometry and a switching feedback controller were used to accomplish ex vivo and in vivo hyperthermia evaluations of the probe. RESULTS: Both exposimetry and k-space simulation results demonstrated acceptable agreement within 9%. With a desired temperature plateau of 43.0°C, ex vivo and in vivo controlled hyperthermia experiments showed that the MRI temperature at the steady state was 42.9 ± 0.38°C and 43.1 ± 0.80°C, respectively, for 20 minutes of heating. CONCLUSION: Unlike conventional computational methods, the k-space method provides a powerful tool to predict pressure wavefield in large scale, 3D, inhomogeneous and coarse grid tissue models. Noninvasive MRI thermometry supports the efficacy of this probe and the feedback controller in an in vivo hyperthermia treatment of canine prostate

Altered Host Immunity, Human T Lymphotropic Virus Type I Replication, and Risk of Adult T-Cell Leukemia/Lymphoma: A Prospective Analysis from the ATL Cohort Consortium

Background: Adult T-cell leukemia/lymphoma (ATL) is a rare and often fatal outcome of infection with human T-lymphotropic virus type I (HTLV-I). Altered host immunity in HTLV-I carriers has been postulated as a risk factor for ATL, but is not well understood. Methods: We prospectively examined well-validated serologic markers of HTLV-I pathogenesis and host immunity in 53 incident ATL cases and 150 carefully matched asymptomatic HTLV-I carriers from eight population-based studies in Japan, Jamaica, the United States and Brazil. We used multivariable conditional logistic regression, conditioned on the matching factors (cohort/race, age, sex, and sample collection year), to evaluate the biomarkers’ associations with ATL in all subjects and by years (≤5, >5) from blood draw to ATL diagnosis. Results: In the pooled population, above-median soluble interleukin-2-receptor-alpha levels (sIL2R, v. ≤ median; odds ratio (OR), 95% confidence interval (CI)=4.08, 1.47-11.29) and anti-Tax seropositivity (anti-Tax; OR, 95% CI=2.97, 1.15-7.67), which indicate T cell activation and HTLV-I replication, respectively, were independently associated with an increased ATL risk. Above-median total immunoglobulin E levels (v. ≤ median; OR, 95% CI=0.45, 0.19-1.06), which indicate type 2 (B cell) activation, predicted a lower ATL risk. The sIL2R and anti-Tax associations with ATL were stronger in samples collected ≤5 years pre-diagnosis. Conclusions: The biomarker profile predictive of ATL risk suggests a role for heightened T cell activation and HTLV-I replication and diminished type 2 immunity in the etiology of ATL in HTLV-I carriers. Translation of these findings to clinical risk prediction or early ATL detection requires further investigation. Acknowledgements: This abstract is presented on behalf of the ATL Cohort Consortium

High levels of surgical antibiotic prophylaxis: implications for hospital-based antibiotic stewardship in Sierra Leone

OBJECTIVE: Despite the impact of inappropriate prescribing on antibiotic resistance, data on surgical antibiotic prophylaxis in sub-Saharan Africa are limited. In this study, we evaluated antibiotic use and consumption in surgical prophylaxis in 4 hospitals located in 2 geographic regions of Sierra Leone. METHODS: We used a prospective cohort design to collect data from surgical patients aged 18 years or older between February and October 2021. Data were analyzed using Stata version 16 software. RESULTS: Of the 753 surgical patients, 439 (58.3%) were females, and 723 (96%) had received at least 1 dose of antibiotics. Only 410 (54.4%) patients had indications for surgical antibiotic prophylaxis consistent with local guidelines. Factors associated with preoperative antibiotic prophylaxis were the type of surgery, wound class, and consistency of surgical antibiotic prophylaxis with local guidelines. Postoperatively, type of surgery, wound class, and consistency of antibiotic use with local guidelines were important factors associated with antibiotic use. Of the 2,482 doses administered, 1,410 (56.8%) were given postoperatively. Preoperative and intraoperative antibiotic use was reported in 645 (26%) and 427 (17.2%) cases, respectively. The most commonly used antibiotic was ceftriaxone 949 (38.2%) with a consumption of 41.6 defined daily doses (DDD) per 100 bed days. Overall, antibiotic consumption was 117.9 DDD per 100 bed days. The Access antibiotics had 72.7 DDD per 100 bed days (61.7%). CONCLUSIONS: We report a high rate of antibiotic consumption for surgical prophylaxis, most of which was not based on local guidelines. To address this growing threat, urgent action is needed to reduce irrational antibiotic prescribing for surgical prophylaxis

Mechanisms of international influence on domestic elite sport policy

In the analysis of sport policy the permeability of domestic policy processes and the significance of non-domestic policy influences is increasingly acknowledged. There is also a growing awareness of the role of domestic institutional arrangements in mediating influences external to the domestic policy system. Taking the interaction between non-domestic influences and domestic policy processes as its starting point the article evaluates, in relation to elite sport, the variety of mechanisms that have been identified as linking the domestic and non-domestic policy spheres. It is argued that the mechanisms vary in relation to the locus of initiative, the basis of engagement, the key relationships and the nature of power relationships. It is also argued that in many countries in relation to elite sport policy there is a dual process in operation of domestically initiated policy learning and non-domestically initiated policy harmonisation through policy regimes