Interdisciplinary working in public health research: a proposed good practice checklist.

Background: Guidance on how different disciplines from the natural, behavioural and social sciences can collaborate to resolve complex public health problems is lacking. This article presents a checklist to support researchers and principle investigators to develop and implement interdisciplinary collaborations. Methods: Fourteen individuals, representing 10 disciplines, participated in in-depth interviews to explore the strengths and challenges of working together on an interdisciplinary project to identify the determinants of substance use and gambling disorders, and to make recommendations for future interdisciplinary teams. Data were analysed thematically and a checklist was derived from insights offered by participants during interview and discussion among the authors on the implications of findings. Results: Participants identified 18 scientific, interactional and structural strengths and challenges of interdisciplinary research. These findings were used to develop an 18-item BASICS checklist to support future interdisciplinary collaborations. The five domains of the checklist are: (i) Blueprint, (ii) Attitudes, (iii) Staffing, (iv) Interactions and (v) Core Science. Conclusion: Interdisciplinary work has the potential to advance public health science but the numerous challenges should not be underestimated. Use of a checklist, such as BASICS, when planning and managing projects may help future collaborations to avoid some of the common pitfalls of interdisciplinary research.

The Epidemiology of Staphylococcus aureus and Panton-Valentine Leucocidin (pvl) in Central Australia, 2006-2010.

BACKGROUND: The Central Australian Indigenous population has a high incidence of Staphylococcus aureus bacteremia (SAB) but little is known about the local molecular epidemiology. METHODS: Prospective observational study of bacteremic and nasal colonizing S.aureus isolates between June 2006 to June 2010. All isolates underwent single nucleotide polymorphism (SNP) genotyping and testing for the presence of the Panton-Valentine Leucocidin (pvl) gene. RESULTS: Invasive isolates (n = 97) were predominantly ST93 (26.6 %) and pvl positive (54.3 %), which was associated with skin and soft tissue infections (OR 4.35, 95 % CI 1.16, 16.31). Non-multiresistant MRSA accounted for 31.9 % of bacteremic samples and showed a trend to being healthcare associated (OR 2.16, 95 % CI 0.86, 5.40). Non-invasive isolates (n = 54) were rarely ST93 (1.9 %) or pvl positive (7.4 %). CONCLUSIONS: In Central Australia, ST93 was the dominant S.aureus clone, and was frequently pvl positive and associated with an aggressive clinical phenotype. Whether non-nasal carriage is more important with invasive clones or whether colonization occurs only transiently remains to be elucidated.

Adjacent Fe-Vacancy Interactions as the Origin of Room Temperature Ferromagnetism in (In(1-x)Fe(x))2O3.

Dilute magnetic semiconductors (DMSs) show great promise for applications in spin-based electronics, but in most cases continue to elude explanations of their magnetic behavior. Here, we combine quantitative x-ray spectroscopy and Anderson impurity model calculations to study ferromagnetic Fe-substituted In2O3 films, and we identify a subset of Fe atoms adjacent to oxygen vacancies in the crystal lattice which are responsible for the observed room temperature ferromagnetism. Using resonant inelastic x-ray scattering, we map out the near gap electronic structure and provide further support for this conclusion. Serving as a concrete verification of recent theoretical results and indirect experimental evidence, these results solidify the role of impurity-vacancy coupling in oxide-based DMSs.

GAL-021, a new intravenous BKCa-channel blocker, is well tolerated and stimulates ventilation in healthy volunteers.

BACKGROUND: Potassium-channels in the carotid body and the brainstem are important regulators of ventilation. The BKCa-channel contains response elements for CO, O2, and CO2. Its block increases carotid body signalling, phrenic nerve activity, and respiratory drive. GAL-021, a new BKCa-channel blocker, increases minute ventilation in rats and non-human primates. This study assessed the single-dose safety, tolerability, pharmacokinetics (PKs), and pharmacodynamics (PDs) of GAL-021 in healthy volunteers. METHODS: Thirty subjects participated in a nine-period, randomized, double-blinded, placebo-controlled, crossover, ascending dose, first-in-human study with i.v. infusions of 0.1-0.96 mg kg(-1) h(-1) for 1 h and intermediate doses up to 4 h. RESULTS: Adverse event rates were generally similar among dose levels and between placebo- and GAL-021-treated subjects. At higher GAL-021 doses, a mild/moderate burning sensation at the infusion site occurred during the infusion. No clinically significant changes in vital signs or clinical chemistries were noted. Minute ventilation increased (AUE0-1 h ≈ 16%, P<0.05) and end-tidal carbon dioxide ([Formula: see text]) decreased (AUE0-1 h ≈ 6%, P<0.05) during the first hour at 0.96 mg kg(-1) h(-1) with 1/2-maximal [Formula: see text] and [Formula: see text]-change occurring by 7.5 min. Drug concentration rose rapidly during the infusion and decreased rapidly initially (distribution t1/2 of 30 min) and then more slowly (terminal t1/2 of 5.6 h). CONCLUSIONS: GAL-021 was safe and generally well tolerated with adverse events comparable with placebo except for an infusion site burning sensation. GAL-021 stimulated ventilation at the highest doses suggesting that greater infusion rates may be required for maximum PD effects. GAL-021 had PK characteristics consistent with an acute care medication.

Environmental determinants of Ixodes ricinus ticks and the incidence of Borrelia burgdorferi sensu lato, the agent of Lyme borreliosis, in Scotland.

Lyme borreliosis (LB) is the most common arthropod-borne disease of humans in the Northern hemisphere. In Europe, the causative agent, Borrelia burgdorferi sensu lato complex, is principally vectored by Ixodes ricinus ticks. The aim of this study was to identify environmental factors influencing questing I. ricinus nymph abundance and B. burgdorferi s.l. infection in questing nymphs using a large-scale survey across Scotland. Ticks, host dung and vegetation were surveyed at 25 woodland sites, and climatic variables from a Geographical Information System (GIS) were extracted for each site. A total of 2397 10 m2 transect surveys were conducted and 13 250 I. ricinus nymphs counted. Questing nymphs were assayed for B. burgdorferi s.l. and the average infection prevalence was 5·6% (range 0·8-13·9%). More questing nymphs and higher incidence of B. burgdorferi s.l. infection were found in areas with higher deer abundance and in mixed/deciduous compared to coniferous forests, as well as weaker correlations with season, altitude, rainfall and ground vegetation. No correlation was found between nymph abundance and infection prevalence within the ranges encountered. An understanding of the environmental conditions associated with tick abundance and pathogen prevalence may be used to reduce risk of exposure and to predict future pathogen prevalence and distributions under environmental changes.

A frame shift mutation in the PMP22 gene in hereditary neuropathy with liability to pressure palsies.

Hereditary neuropathy with liability to pressure palsies (HNPP) has been a associated with a deletion of 1.5 megabases of chromosome 17p. One of four biopsy proven HNPP families that we have studied did not possess this deletion. As the deleted DNA region includes the coding region for a peripheral myelin gene (PMP22), we used single strand conformation analysis to examine this gene for mutations in the non-deleted HNPP family. An abnormal fragment in exon 1 was identified, and sequencing revealed a two base pair deletion in all affected family members. The deletion results in a frame shift, providing strong evidence that this gene has an important role in the pathogenesis of the disease.

Factors affecting turnaround time of SARS-CoV-2 sequencing for inpatient infection prevention and control decision making: analysis of data from the COG-UK HOCI study.

BACKGROUND: Barriers to rapid return of sequencing results can affect the utility of sequence data for infection prevention and control decisions. AIM: To undertake a mixed-methods analysis to identify challenges that sites faced in achieving a rapid turnaround time (TAT) in the COVID-19 Genomics UK Hospital-Onset COVID-19 Infection (COG-UK HOCI) study. METHODS: For the quantitative analysis, timepoints relating to different stages of the sequencing process were extracted from both the COG-UK HOCI study dataset and surveys of study sites. Qualitative data relating to the barriers and facilitators to achieving rapid TATs were included from thematic analysis. FINDINGS: The overall TAT, from sample collection to receipt of sequence report by infection control teams, varied between sites (median 5.1 days, range 3.0-29.0 days). Most variation was seen between reporting of a positive COVID-19 polymerase chain reaction (PCR) result to sequence report generation (median 4.0 days, range 2.3-27.0 days). On deeper analysis, most of this variability was accounted for by differences in the delay between the COVID-19 PCR result and arrival of the sample at the sequencing laboratory (median 20.8 h, range 16.0-88.7 h). Qualitative analyses suggest that closer proximity of sequencing laboratories to diagnostic laboratories, increased staff flexibility and regular transport times facilitated a shorter TAT. CONCLUSION: Integration of pathogen sequencing into diagnostic laboratories may help to improve sequencing TAT to allow sequence data to be of tangible value to infection control practice. Adding a quality control step upstream to increase capacity further down the workflow may also optimize TAT if lower quality samples are removed at an earlier stage.

Landscape genetics of a top neotropical predator.

Habitat loss and fragmentation as a consequence of human activities is a worldwide phenomenon and one of the major threats to global biodiversity. Habitat loss and fragmentation is particularly a concern in the biodiverse tropics, where deforestation is occurring at unprecedented rates. Although insects are one of the most diverse and functionally important groups in tropical ecosystems, the quantitative effect of landscape features on their gene flow remains unknown. Here, we used a robust landscape genetics approach to quantify the effect of ten landscape features (deforestation, mature forests, other forest types, the River Chagres, streams, stream banks, roads, sea, lakes and swamps) and interactions between them, on the gene flow of a neotropical forest keystone species, the army ant Eciton burchellii. The influence of landscape on E. burchellii's gene flow reflected the different dispersal capability of its sexes; aerial for males and pedestrian for females, and the different depths of population history inferred from microsatellites and mitochondrial DNA. In contrast to the gene flow-facilitating effect of mature forests, deforested areas were found to be strong barriers for E. burchellii's gene flow. Other forest types were found to be gene flow facilitators but only when interacting with mature secondary forests, therefore indicating the importance of mature forests for the survival of E. burchelii and its associate species. The River Chagres was identified as a major historical gene flow barrier for E. burchellii, suggesting that an important loss of connectivity may occur because of large artificial waterways such as the Panama Canal.

Benefits associated with a broad selection of dosage strengths for recombinant factor VIII products.

Factor VIII (FVIII) concentrates for haemophilia A patients are dosed according to body weight. This results in a continuous range of prescribed doses, which challenges pharmacies to find dosage strengths closest to the prescribed dose while utilizing the least number of vials. This study was conducted to determine whether a broader selection of FVIII dosage strengths results in improved dispensing accuracy and an increased number of single-vial users. This research retrospectively analyzed a US pharmacy database of prescriptions filled in 2008. Recombinant FVIII (rFVIII) therapies were classified by the range of dosage strengths offered in 2008: Group 1 had three dosage strengths; Group 2 had four dosage strengths; and Group 3 had six dosage strengths. A total of 76,584 dispensed doses of rFVIII for 1,244 patients were included in this analysis. Dispensing accuracy (calculated as both the absolute and relative difference between dispensed and prescribed dose) was significantly better for Group 3 (23.2 IU, 1.2%) than Groups 1 (33.5 IU, 1.6%) and 2 (50.2 IU, 2.4%) (both P < 0.01). In addition, the average number of unique actual rFVIII potencies dispensed per month was highly correlated (-0.977) with dispensing accuracy for each dosage strength group. Among Groups 1, 2 and 3, 23.0%, 44.9% and 73.4% of patients, respectively, had at least one single vial option dispensed (P < 0.0001). A broader selection of rFVIII dosage strengths and more actual rFVIII potencies were associated with improved dispensing accuracy and more single-vial users. This may translate into less waste, cost savings, increased convenience and improved adherence to physician-prescribed regimens.

Retrospective analysis of differences in annual factor VIII utilization among haemophilia A patients.

Finding differences in drug utilization patterns within rare patient populations is challenging without access to a large sample. Our objective was to identify patient and treatment-related factors associated with differences in annual recombinant factor VIII (rFVIII) utilization in a large cohort of haemophilia A patients. This retrospective analysis utilized a large, US specialty pharmacy dispensing database from January 2006 to September 2009. Differences in median annual FVIII utilization (IU kg(-1) year(-1)) by age, severity, treatment regimen, rFVIII product type and health insurance plan were tested using non-parametric statistics and regression analysis. A total of 1011 haemophilia A patients were included in the overall analysis. Severe haemophilia patients had higher median annual FVIII utilization than mild/moderate patients (P < 0.0001). Median annual FVIII utilization was also significantly different between treatment regimens (episodic = 1429 IU kg(-1) year(-1) vs. prophylaxis = 3993 IU kg(-1) year(-1) for severe patients, P < 0.0001). Children (0-12 years old), adolescents (13-18 years old) and adults (19+ years old) with severe haemophilia A receiving prophylaxis utilized 4588, 4082 and 3223 IU kg(-1) year(-1) (P < 0.0001). After controlling for age, severity, treatment regimen and insurance type, regression analysis revealed B domain-deleted recombinant FVIII (BDD-rFVIII) was associated with 33% higher FVIII consumption compared with full-length recombinant FVIII (FL-rFVIII) (P = 0.0172). Similar results were also seen when matching BDD-rFVIII and FL-rFVIII patients. Health insurance type was not associated with annual FVIII utilization. As expected, age, severity and treatment regimen were significantly associated with FVIII utilization. After controlling for confounders, patients receiving FL-rFVIII prophylactically were associated with lower annual FVIII utilization compared with patients receiving BDD-rFVIII prophylactically.

Patient and parent preferences for haemophilia A treatments.

Little is known about the relative importance of factor VIII (FVIII) treatment attributes to haemophilia A patients and their willingness to accept trade-offs among these attributes. To quantify patient and parent preferences for FVIII treatments and compare the relative importance of treatment attributes. Adult patients and parents of children with severe haemophilia A in the US completed a web-enabled, choice-format conjoint survey that presented a series of 12 trade-off questions, each including a pair of hypothetical treatment profiles. Each profile was defined by percent of bleeds stopped with one or two infusions, chance of developing an inhibitor, risk of viral infection, preparation volume, dosage strengths available, and history of supply shortage. Trade-off questions were based on a D-optimal experimental design. Preference weights for attribute levels were estimated using random-parameters logit. One hundred and forty seven subjects completed the survey. Over the ranges of attribute levels included in the study, risk of viral infection was the most important attribute. Remaining attributes were ranked in decreasing order of importance as follows: chance of developing an inhibitor, dosage strengths available, percent of bleeds stopped with one or two infusions, history of supply shortage, and preparation volume. Risk of viral infection was 6.0 times as important as percent of bleeds stopped with one or two infusions and 2.7 times as important as the chance of developing an inhibitor. While risk of viral infection was the most important attribute, this research demonstrates that many FVIII treatment attributes are important in the decision-making process.

The oldest bryozoans: new evidence from the early ordovician.

An abundant, previously problematic fossil from the Lower Ordovician (Canadian) Black Rock limestone of the Ozark Uplift area is an undescribed dianulitid bryozoan. It is believed to be the oldest unquestionable bryozoan known. The growth morphology varies widely and is believed to be environmentally influenced.

Predicting the need for early amputation in ballistic mangled extremity injuries.

BACKGROUND: Despite modern advances, amputation is still a commonly performed operation in war. It is often difficult to decide whether to amputate after high-energy trauma to the lower extremity. To help guide this assessment, scoring systems have been developed with amputation threshold values. These studies were all conducted on a civilian population, encompassing a wide range of ages and methods of injury. The evidence for their sensitivity and specificity is inconclusive. The aim of this study was to assess the validity of the mangled extremity severity score (MESS), the only verified score, in a population of UK military patients with ballistic mangled extremity injuries. METHODS: We identified from the prospectively kept Joint Theater Trauma Registry all patients who had sustained ballistic lower limb open fractures during the recent conflicts in Iraq and Afghanistan (May 2003-April 2008). Demographics were assessed using both the trauma audit and the hospital notes. Patients were retrospectively evaluated with the MESS system for lower extremity trauma. Those that required an amputation were compared with those that had successful limb salvage. RESULTS: Seventy-seven military patients with 86 limbs who had ballistic mangled extremity injuries were identified, 22 of whom required amputation. The MESS did not help to decide whether or not an amputation was appropriate and in particular, the age was not relevant. A skeletal score of 4, while being associated with a higher amputation rate, was not predictive of its need. Most amputations were performed when an ischemic limb was present, and the general condition of the casualty precluded the lengthy reconstruction required for salvage. CONCLUSIONS: The management of ballistic extremity injuries in military patients should be considered separate to that of civilians with high-energy trauma extremity injuries. The authors have identified important factors in the management, in particular the need for early amputation, of the military mangled extremity.

Screening for dyslexia, dyspraxia and Meares-Irlen syndrome in higher education.

This study reports a comparison of screening tests for dyslexia, dyspraxia and Meares-Irlen (M-I) syndrome in a Higher Education setting, the University of Worcester. Using a sample of 74 volunteer students, we compared the current tutor-delivered battery of 15 subtests with a computerized test, the Lucid Adult Dyslexia Screening test (LADS), and both of these with data on assessment outcomes. The sensitivity of this tutor battery was higher than LADS in predicting dyslexia, dyspraxia or M-I syndrome (91% compared with 66%) and its specificity was lower (79% compared with 90%). Stepwise logistic regression on these tests was used to identify a better performing subset of tests, when combined with a change in practice for M-I syndrome screening. This syndrome itself proved to be a powerful discriminator for dyslexia and/or dyspraxia, and we therefore recommend it as the first stage in a two-stage screening process. The specificity and sensitivity of the new battery, the second part of which comprises LADS plus four of the original tutor delivered subtests, provided the best overall performance: 94% sensitivity and 92% specificity. We anticipate that the new two-part screening process would not take longer to complete.

Landscape features affect gene flow of Scottish Highland red deer (Cervus elaphus).

Landscape features have been shown to strongly influence dispersal and, consequently, the genetic population structure of organisms. Studies quantifying the effect of landscape features on gene flow of large mammals with high dispersal capabilities are rare and have mainly been focused at large geographical scales. In this study, we assessed the influence of several natural and human-made landscape features on red deer gene flow in the Scottish Highlands by analysing 695 individuals for 21 microsatellite markers. Despite the relatively small scale of the study area (115 x 87 km), significant population structure was found using F-statistics (F(ST) = 0.019) and the program structure, with major differentiation found between populations sampled on either side of the main geographical barrier (the Great Glen). To assess the effect of landscape features on red deer population structure, the ArcMap GIS was used to create cost-distance matrices for moving between populations, using a range of cost values for each of the landscape features under consideration. Landscape features were shown to significantly affect red deer gene flow as they explained a greater proportion of the genetic variation than the geographical distance between populations. Sea lochs were found to be the most important red deer gene flow barriers in our study area, followed by mountain slopes, roads and forests. Inland lochs and rivers were identified as landscape features that might facilitate gene flow of red deer. Additionally, we explored the effect of choosing arbitrary cell cost values to construct least cost-distance matrices and described a method for improving the selection of cell cost values for a particular landscape feature.

Ultradian activity rhythms in large groups of newly hatched chicks (Gallus gallus domesticus).

A clutch of young chicks housed with a mother hen exhibit ultradian (within day) rhythms of activity corresponding to the brooding cycle of the hen. In the present study clear evidence was found of ultradian activity rhythms in newly hatched domestic chicks housed in groups larger than natural clutch size without a mother hen or any other obvious external time-keeper. No consistent synchrony was found between groups housed in different pens within the same room. The ultradian rhythms disappeared with time and little evidence of group rhythmicity remained by the third night. This disappearance over time suggests that the presence of a mother hen may be pivotal for the long-term maintenance of these rhythms. The ultradian rhythm of the chicks may also play an important role in the initiation of brooding cycles during the behavioural transition of the mother hen from incubation to brooding. Computer simulations of individual activity rhythms were found to reproduce the observations made on a group basis. This was achievable even when individual chick rhythms were modelled as independent of each other, thus no assumptions of social facilitation are necessary to obtain ultradian activity rhythms on a group level.

Patient-driven hand hygiene audit process at a regional cancer center.

A patient-driven hand hygiene compliance audit strategy was piloted in a Canadian provincial cancer agency during routine provision of cancer outpatient care by health care providers (physicians, nurses, and health care aides) under conditions where the deployment of an independent external auditor was not feasible. The results of the audit suggest the feasibility of this approach as a routine institutional performance metric.

Evidence for non-genomic transmission of ecological information via maternal behavior in female rats.

Maternal behavior is flexible and programs offspring development. Using a novel manipulation, we demonstrate that rat maternal behavior is sensitive to ecologically relevant stimuli. Long-Evans hooded rat dams (F0) and pups were exposed to a predator condition (cat odor) or a control condition (no odor) for 1 h on the day of parturition. Predator-exposed F0 dams displayed significantly more maternal behavior (licking/grooming, arched-back nursing) relative to control-exposed dams across five subsequent observation days. Female offspring (F1) were raised to adulthood, bred and maternal behavior was observed. F1 dams reared by a predator-exposed F0 dam displayed significantly higher maternal behavior relative to F1 dams reared by a control-exposed F0 dam across 5 days of observation. Increased levels of maternal behavior in predator-reared (PR) F1 dams were evident even in F1 females that had been cross-fostered (CF) from a control-exposed F0 dam, suggesting a non-genomic transmission of increased levels of maternal behavior. Lactating PR F1 dams had significantly elevated estrogen receptor alpha and beta mRNA in the medial preoptic area relative to control-reared (CR) F1 dams. Furthermore, among CR F1 dams, there was no significant difference between those dams that had been CF from predator-exposed F0 dams and those that had been sham CF. These results support the hypothesis that flexible rat maternal behavior can shape offspring development according to current environmental conditions. The results also suggest that estrogen signaling may be part of an epigenetic mechanism by which changes in maternal behavior are passed from F0 to F1 dams.

Vitamin D binding protein sequesters monomeric actin in the circulation of the rat.

Plasma vitamin D binding protein (DBP) may scavenge actin released during cell lysis. We examined the plasma disappearance and tissue appearance of 125I-DBP, 125I-G-actin, and the DBP-G-actin complex after their intravenous administration to rats. The plasma disappearance of DBP and DBP-actin were indistinguishable, with rapid initial (t1/2 = 2.6 h) and slower second (t1/2 = 7 h) slopes. After 125I-G-actin (nanomole) injection, plasma disappearance paralleled that of DBP and DBP-actin. All injected actin was associated with DBP, without evidence of free actin, actin-gelsolin complexes or actin oligomers. Tissue appearances of 125I-apo-DBP (apo) or holo-DBP were similar, with highest accumulations in perfused liver, kidney, and skeletal muscle. Although more complex phenomena (plasma entry of F-actin and intracellular actin binding proteins) would occur in vivo after cell lysis, our results suggest a role for DBP in the sequestration and disposition of actin monomers in the circulation.

Long-term prognosis of multiple sclerosis in Australia.

Long-term survival and progression of disability in multiple sclerosis have not been studied previously in Australia. We report the findings in a cohort of 159 patients from Newcastle. Median survival time from onset of symptoms to death was 42 years. When expected survival rates are compared with those of the Australian population, there is approximately a 10% reduction in survival time in multiple sclerosis patients, after 20 years or more from disease onset. The expected time to reach DSS 3 and DSS 6 was 7 years and 27 years respectively. Survival time of multiple sclerosis patients and rate of progression of the disease are similar in the Northern and Southern Hemispheres.