Mental health and employment outcomes in working-age US adults, 2010-2019.

BACKGROUND: Individuals with severe mental illness experience greater unemployment and barriers to workforce re-entry. However, less is known about additional indicators of employment stability for individuals across mental illness severity. AIMS: This study aims to examine associations between mental illness severity, use and adequacy of mental health treatment, and indicators of employment stability. METHODS: In this repeated cross-sectional study, 2010-2019 data from the U.S. National Survey of Drug Use and Health were used to construct multivariate logistic regression models predicting the odds of part-time employment, past-year work interruption, number of past-year employers, and past-month health-related work absence by mental illness severity and adequacy of mental health treatment. RESULTS: Compared to individuals with no mental illness, those with any and severe mental illness had significantly higher odds of part-time employment (adjusted odds ratios [AORs] = 1.51 and 2.16, 95% confidence intervals [CIs] 1.4-1.6 and 2.0-2.3), multiple past-year employers (AORs = 1.78 and 2.34, CIs 1.7-1.9 and 2.1-2.6), past-year work interruption (AORs = 1.69 and 2.20, CIs 1.6-1.8 and 2.1-2.4), and >7 days of past-month work absence (AORs = 2.51 and 3.82, CIs 2.3-2.8 and 3.3-4.5). Among respondents with mental illness, perceived inadequacy of mental treatment predicted higher odds of all adverse employment outcomes. CONCLUSIONS: Compared to those with no mental illness, individuals with mental illness of any severity have higher odds of employment instability. Policy and programmatic support aimed at addressing the needs of individuals with mental illness, including access to adequate mental health treatment, are needed to facilitate continued, competitive employment.

Dihydroceramide- and ceramide-profiling provides insights into human cardiometabolic disease etiology.

Metabolic alterations precede cardiometabolic disease onset. Here we present ceramide- and dihydroceramide-profiling data from a nested case-cohort (type 2 diabetes [T2D, n = 775]; cardiovascular disease [CVD, n = 551]; random subcohort [n = 1137]) in the prospective EPIC-Potsdam study. We apply the novel NetCoupler-algorithm to link a data-driven (dihydro)ceramide network to T2D and CVD risk. Controlling for confounding by other (dihydro)ceramides, ceramides C18:0 and C22:0 and dihydroceramides C20:0 and C22:2 are associated with higher and ceramide C20:0 and dihydroceramide C26:1 with lower T2D risk. Ceramide C16:0 and dihydroceramide C22:2 are associated with higher CVD risk. Genome-wide association studies and Mendelian randomization analyses support a role of ceramide C22:0 in T2D etiology. Our results also suggest that (dh)ceramides partly mediate the putative adverse effect of high red meat consumption and benefits of coffee consumption on T2D risk. Thus, (dihydro)ceramides may play a critical role in linking genetic predisposition and dietary habits to cardiometabolic disease risk.

Comparison of droplet spread in standard and laminar flow operating theatres: SPRAY study group.

BACKGROUND: Reducing COVID-19 transmission relies on controlling droplet and aerosol spread. Fluorescein staining reveals microscopic droplets. AIM: To compare the droplet spread in non-laminar and laminar air flow operating theatres. METHODS: A 'cough-generator' was fixed to a theatre trolley at 45°. Fluorescein-stained 'secretions' were projected on to a series of calibrated targets. These were photographed under UV light and 'source detection' software measured droplet splatter size and distance. FINDINGS: The smallest droplet detected was ∼120 µm and the largest ∼24,000 µm. An average of 25,862 spots was detected in the non-laminar theatre, compared with 11,430 in the laminar theatre (56% reduction). The laminar air flow mainly affected the smaller droplets (<1000 µm). The surface area covered with droplets was: 6% at 50 cm, 1% at 2 m, and 0.5% at 3 m in the non-laminar air flow; and 3%, 0.5%, and 0.2% in the laminar air flow, respectively. CONCLUSION: Accurate mapping of droplet spread in clinical environments is possible using fluorescein staining and image analysis. The laminar air flow affected the smaller droplets but had limited effect on larger droplets in our 'aerosol-generating procedure' cough model. Our results indicate that the laminar air flow theatre requires similar post-surgery cleaning to the non-laminar, and staff should consider full personal protective equipment for medium- and high-risk patients.

Association of mitochondrial DNA copy number with metabolic syndrome and type 2 diabetes in 14 176 individuals.

BACKGROUND: Mitochondria play an important role in cellular metabolism, and their dysfunction is postulated to be involved in metabolic disturbances. Mitochondrial DNA is present in multiple copies per cell. The quantification of mitochondrial DNA copy number (mtDNA-CN) might be used to assess mitochondrial dysfunction. OBJECTIVES: We aimed to investigate the cross-sectional association of mtDNA-CN with type 2 diabetes and the potential mediating role of metabolic syndrome. METHODS: We examined 4812 patients from the German Chronic Kidney Disease (GCKD) study and 9364 individuals from the Cooperative Health Research in South Tyrol (CHRIS) study. MtDNA-CN was measured in whole blood using a plasmid-normalized qPCR-based assay. RESULTS: In both studies, mtDNA-CN showed a significant correlation with most metabolic syndrome parameters: mtDNA-CN decreased with increasing number of metabolic syndrome components. Furthermore, individuals with low mtDNA-CN had significantly higher odds of metabolic syndrome (OR = 1.025; 95% CI = 1.011-1.039, P = 3.19 × 10-4 , for each decrease of 10 mtDNA copies) and type 2 diabetes (OR = 1.027; 95% CI = 1.012-1.041; P = 2.84 × 10-4 ) in a model adjusted for age, sex, smoking and kidney function in the meta-analysis of both studies. Mediation analysis revealed that the association of mtDNA-CN with type 2 diabetes was mainly mediated by waist circumference in the GCKD study (66%) and by several metabolic syndrome parameters, especially body mass index and triglycerides, in the CHRIS study (41%). CONCLUSIONS: Our data show an inverse association of mtDNA-CN with higher risk of metabolic syndrome and type 2 diabetes. A major part of the total effect of mtDNA-CN on type 2 diabetes is mediated by obesity parameters.

The effects of Hurricane Sandy on trauma center admissions.

BACKGROUND: Hurricane Sandy was a particularly unusual storm with regard to both size and location of landfall. The storm landed in New Jersey, which is unusual for a tropical storm of such scale, and created hazardous conditions which caused injury to residents during the storm and in the months following. This study aims to describe differences in trauma center admissions and patterns of injury during this time period when compared to a period with no such storm. METHODS: Data were collected for this study from patients who were admitted to the trauma center at Morristown Medical Center during Hurricane Sandy or the ensuing cleanup efforts (patients admitted between 29 October 2012 and 27 December 2012) as well as a control group consisting of all patients admitted to the trauma center between 29 October 2013 and 27 December 2013. Patient information was collected to compare the admissions of the trauma center during the period of the storm and cleanup to the control period. RESULTS: A total of 419 cases were identified in the storm and cleanup period. 427 were identified for the control. Striking injuries were more common in the storm and cleanup group by 266.7% (p = 0.0107); cuts were more common by 650.8% (p = 0.0044). Medical records indicate that many of these injuries were caused by Hurricane Sandy. Self-inflicted injuries were more common by 301.3% (p = 0.0294). There were no significant differences in the total number of patients, mortality, or injury severity score between the two cohorts. CONCLUSION: The data we have collected show that the conditions caused by Hurricane Sandy and the following cleanup had a significant effect on injury patterns, with more patients having been injured by being struck by falling or thrown objects, cut while using tools, or causing self-inflicted injuries. These changes, particularly during the cleanup period, are indicative of environmental changes following the storm which increase these risks of injury.

32-channel time-correlated-single-photon-counting system for high-throughput lifetime imaging.

Time-Correlated Single Photon Counting (TCSPC) is a very efficient technique for measuring weak and fast optical signals, but it is mainly limited by the relatively "long" measurement time. Multichannel systems have been developed in recent years aiming to overcome this limitation by managing several detectors or TCSPC devices in parallel. Nevertheless, if we look at state-of-the-art systems, there is still a strong trade-off between the parallelism level and performance: the higher the number of channels, the poorer the performance. In 2013, we presented a complete and compact 32 × 1 TCSPC system, composed of an array of 32 single-photon avalanche diodes connected to 32 time-to-amplitude converters, which showed that it was possible to overcome the existing trade-off. In this paper, we present an evolution of the previous work that is conceived for high-throughput fluorescence lifetime imaging microscopy. This application can be addressed by the new system thanks to a centralized logic, fast data management and an interface to a microscope. The new conceived hardware structure is presented, as well as the firmware developed to manage the operation of the module. Finally, preliminary results, obtained from the practical application of the technology, are shown to validate the developed system.

Behaviours of concern following moderate to severe traumatic brain injury in individuals living in the community.

PRIMARY OBJECTIVE: Behaviours of Concern (BoC) following traumatic brain injury (TBI) have a significant negative impact on the daily functioning and quality of life for the individual and their family. However, there has been limited research examining the nature and severity of BoC beyond the acute recovery period, including the perspective of the individual with TBI as well as close others (COs). METHODS AND PROCEDURE: Eighty-nine individuals with predominantly severe TBI, at a mean of 11.4 years' post-injury, were identified through a no-fault accident compensation system database. Structured interviews were completed with 65 individuals with TBI, and 62 COs. Current BoC were documented using the Overt Behaviour Scale (OBS). MAIN OUTCOMES AND RESULTS: 70.5% of participants exhibited BoC on the OBS, with an average of 3 behaviours. Verbal aggression and socially inappropriate behaviour were the most common BoC. Self-report of behaviour change was endorsed by 81% of the sample. There was generally poor concordance between the perspectives of the individual with the TBI and their CO. CONCLUSION: Severe BoC, across multiple behaviour types, may be evident many years following predominantly severe TBI. There is a need to provide long-term behaviour support for these individuals.

Further Evidence for Bats as the Evolutionary Source of Middle East Respiratory Syndrome Coronavirus.

The evolutionary origins of Middle East respiratory syndrome (MERS) coronavirus (MERS-CoV) are unknown. Current evidence suggests that insectivorous bats are likely to be the original source, as several 2c CoVs have been described from various species in the family Vespertilionidae Here, we describe a MERS-like CoV identified from a Pipistrellus cf. hesperidus bat sampled in Uganda (strain PREDICT/PDF-2180), further supporting the hypothesis that bats are the evolutionary source of MERS-CoV. Phylogenetic analysis showed that PREDICT/PDF-2180 is closely related to MERS-CoV across much of its genome, consistent with a common ancestry; however, the spike protein was highly divergent (46% amino acid identity), suggesting that the two viruses may have different receptor binding properties. Indeed, several amino acid substitutions were identified in key binding residues that were predicted to block PREDICT/PDF-2180 from attaching to the MERS-CoV DPP4 receptor. To experimentally test this hypothesis, an infectious MERS-CoV clone expressing the PREDICT/PDF-2180 spike protein was generated. Recombinant viruses derived from the clone were replication competent but unable to spread and establish new infections in Vero cells or primary human airway epithelial cells. Our findings suggest that PREDICT/PDF-2180 is unlikely to pose a zoonotic threat. Recombination in the S1 subunit of the spike gene was identified as the primary mechanism driving variation in the spike phenotype and was likely one of the critical steps in the evolution and emergence of MERS-CoV in humans.IMPORTANCE Global surveillance efforts for undiscovered viruses are an important component of pandemic prevention initiatives. These surveys can be useful for finding novel viruses and for gaining insights into the ecological and evolutionary factors driving viral diversity; however, finding a viral sequence is not sufficient to determine whether it can infect people (i.e., poses a zoonotic threat). Here, we investigated the specific zoonotic risk of a MERS-like coronavirus (PREDICT/PDF-2180) identified in a bat from Uganda and showed that, despite being closely related to MERS-CoV, it is unlikely to pose a threat to humans. We suggest that this approach constitutes an appropriate strategy for beginning to determine the zoonotic potential of wildlife viruses. By showing that PREDICT/PDF-2180 does not infect cells that express the functional receptor for MERS-CoV, we further show that recombination was likely to be the critical step that allowed MERS to emerge in humans.

Epidemiological investigation of grass seed foreign body-related disease in dogs of the Riverina District of rural Australia.

OBJECTIVE: To characterise disease presentations caused by grass seed foreign body-related disease (GSFBD) in dogs, identify predisposing risk factors and suggest effective prevention strategies. METHODS: A retrospective, case-control, telephone survey was conducted to obtain information on GSFBD in dogs from the Riverina district of New South Wales (NSW). Additionally, retrospective case records were obtained from Wagga Wagga Veterinary Hospital and Charles Sturt University Veterinary Teaching Hospital over the period July 2006 to October 2011. Signalment, history, investigative strategies, location and severity of lesion(s), cost of therapy, length of hospitalisation, recurrence rate and microbiology data were recorded. RESULTS: Cases (473 dogs) meeting stringent inclusion criteria were identified. GSFBD comprised 2.0% of hospital presentations. Breeds with high-density coats were overrepresented. Otitis externa was the most common manifestation of GSFBD in the general practice (47%). In the referral practice pyothorax was the most common entity (34%). In both practices the range of clinical manifestations was broad, including a small number of dogs with catastrophic intracranial disease. Univariable and multivariable logistic regression analyses demonstrated dogs with GSFBD had 3-fold greater odds of having medium coats than short coats and 5-fold less odds of being groomed. CONCLUSIONS AND CLINICAL RELEVANCE: Grass seeds are a major cause of disease in the dogs of south-west rural NSW, with presentations ranging from mild lameness to severe neurological disease. Some protection from GSFBD was achieved with frequent grooming. Clipping or coat searching without grooming was ineffective as a prevention strategy.

Discovery of a Novel Hepatovirus (Phopivirus of Seals) Related to Human Hepatitis A Virus.

UNLABELLED: Describing the viral diversity of wildlife can provide interesting and useful insights into the natural history of established human pathogens. In this study, we describe a previously unknown picornavirus in harbor seals (tentatively named phopivirus) that is related to human hepatitis A virus (HAV). We show that phopivirus shares several genetic and phenotypic characteristics with HAV, including phylogenetic relatedness across the genome, a specific and seemingly quiescent tropism for hepatocytes, structural conservation in a key functional region of the type III internal ribosomal entry site (IRES), and a codon usage bias consistent with that of HAV. IMPORTANCE: Hepatitis A virus (HAV) is an important viral hepatitis in humans because of the substantial number of cases each year in regions with low socioeconomic status. The origin of HAV is unknown, and no nonprimate HAV-like viruses have been described. Here, we describe the discovery of an HAV-like virus in seals. This finding suggests that the diversity and evolutionary history of these viruses might be far greater than previously thought and may provide insight into the origin and pathogenicity of HAV.

A 16-week randomized controlled trial evaluating the physical activity guidelines for adults with spinal cord injury.

STUDY DESIGN: Randomized controlled trial. OBJECTIVES: To evaluate the effectiveness of the physical activity guidelines (PAG) for adults with spinal cord injury (SCI) to improve aspects of physical fitness. SETTING: Community exercise facility. METHODS: Twenty-three participants (age: 40.4±11.6 years, C1-T11, 12.0±10.0 years post injury) were randomized into PAG training (n=12) or active control (CON, n=11) groups. PAG training was 2x per week for 16 weeks and involved 20 min of aerobic exercise at a moderate to vigorous intensity and three sets of 10 repetitions (at 50-70% 1 repetition maximum; 1RM). Pre- and post-testing included peak exercise and aerobic endurance tests on an arm ergometer and 1RM testing. RESULTS: Nineteen participants (PAG, n=11; CON, n=8) completed the 16-week training program and post-testing. There was a significant (P<0.05) increase in peak aerobic capacity (relative VO2peak: 17.2%, absolute VO2peak: 9.9%) and submaximal power output (26.3%) in the PAG group only. Increases in strength ranged from 11.5-38.9% and were significantly (P<0.05) different from CON for vertical bench press, seated row, and rickshaw press. Adherence to the exercise program was 85.2±8.3% for PAG, 44.4±34.3% for CON (P<0.01). CONCLUSION: The PAG for adults with SCI are sufficient to improve aspects of aerobic and muscular fitness and should be promoted as a means to improve physical capacity. SPONSORSHIP: Ontario Neurotrauma Foundation (ONF), Natural Sciences and Engineering Research Council (NSERC) of Canada.

Exercise equipment preferences among adults with spinal cord injury.

STUDY DESIGN: Cross-sectional. OBJECTIVES: To evaluate exercise equipment preferences and compare cardiometabolic demand for passive hybrid and arm-only exercise among adults with paraplegia (PP) and those with tetraplegia (TP). SETTING: Four community exercise programmes. METHODS: Thirty-six adults (mean age: 41.1±12.1 years) with chronic (11.4±10.7 years post injury) TP (C3-C8; n=17) or PP (T3-T12; n=19) were recruited. Participants completed 20 min of submaximal aerobic exercise at moderate to vigorous intensity on four types of aerobic exercise equipment: arm cycle ergometer (ACE), arm glider (AG), arm-leg recumbent stepper (ALRS), and arm-leg cycle ergometer (ALCE). Participants also completed 3 sets of 10 repetitions of resistance exercise using wall pulleys (WP) and weight stack (WS) equipment. A questionnaire was administered to evaluate equipment preference. Heart rate (HR) and oxygen uptake (VO2) were measured in a subset of participants (n=9) during submaximal aerobic exercise. RESULTS: Arm-only exercise modes were perceived as being safer than passive hybrid exercise modes. There were no differences in perceived enjoyment between equipment types and groups. There were significant group but not equipment differences in HR (TP: 101.4 bpm; PP: 124.9 bpm) and VO2 (TP: 6.5 ml•kg(-1)•min(-1); PP: 10.5 mL•kg(-1)•min(-1)) during submaximal aerobic exercise. CONCLUSION: In this cross-community assessment of exercise equipment preferences after spinal cord injury (SCI), arm-only exercise modes were perceived as safer than hybrid exercise modes and there were no differences between equipment types in physiological responses.

Direct referral and physical activity counselling upon discharge from spinal cord injury rehabilitation.

STUDY DESIGN: Sixteen-week follow-up study. OBJECTIVE: To evaluate the efficacy of referral from a health-care provider to regular exercise combined with 16 weeks of counselling support following discharge from inpatient or outpatient spinal cord injury (SCI) rehabilitation. SETTING: Two rehabilitation centres in Canada. METHODS: Seventeen participants (age 42.1±10.6 years, C3-T12, ASIA impairment score A-C) were recruited at discharge from inpatient (n=9; 5.2±1.3 months post-injury) or outpatient (n=8; 14.2±3.8 months post-injury) rehabilitation and were given a referral for regular exercise. Telephone counselling support was provided and adherence to the prescribed program was monitored for 16 weeks. RESULTS: There was a nonsignificant difference in exercise adherence rates (percentage of available sessions attended) between participants discharged from inpatient (71.4±44.9%) and those from outpatient (39.5±27.2%) rehabilitation programs. The most common barriers to participation were physical health problems (50%) and transportation (36%). An exercise beliefs questionnaire revealed that participants value exercise at discharge from rehabilitation, despite the common report of a relative lack of confidence in their ability to perform or adapt aerobic and resistance exercises to their specific capabilities. CONCLUSION: A system of direct referral and ongoing counselling support following discharge from either inpatient or outpatient SCI rehabilitation appears to encourage sustained participation, although future health promotion strategies should continue to provide specific information about how to adapt and complete aerobic and resistance exercises. SPONSORSHIP: Rick Hansen Institute and Ontario Neurotrauma Foundation.

Chronic inactive pulmonary tuberculosis and treatment sequelae: chest radiographic features.

The chest radiograph (CXR) is a key initial tool in the diagnosis of many lung conditions, including pulmonary tuberculosis (TB). With proper use of anti-tuberculosis drugs, TB can be treated effectively and many CXR changes are limited. However, anti-tuberculosis drugs have not always been available, and in some cases they have not been started early in the disease process. The infection has then been able to take hold and cause significant radiologically visible damage, such as calcification and fibrosis. Before the use of anti-tuberculosis drugs, a variety of surgical techniques were employed to control pulmonary infection, including plombage, oleothorax, phrenic nerve crush and thoracoplasty. Each of these led to distinctive CXR features. This article sets out to describe the CXR features of chronic disease and surgical treatments, as their increasing rarity with the passage of time has meant that they can be misinterpreted. However, with increasing life expectancy and the revival of surgery due to the development of anti-tuberculosis drug resistance, the correct interpretation of these CXR changes is still of importance.

Lower limb injuries caused by improvised explosive devices: proposed 'Bastion classification' and prospective validation.

BACKGROUND: Complex lower limb injury caused by improvised explosive devices (IEDs) has become the signature wounding pattern of the conflict in Afghanistan. Current classifications neither describe this injury pattern well, nor correlate with management. There is need for a new classification, to aid communication between clinicians, and help evaluate interventions and outcomes. We propose such a classification, and present the results of an initial prospective evaluation. PATIENTS AND METHODS: The classification was developed by a panel of military surgeons whilst deployed to Camp Bastion, Afghanistan. Injuries were divided into five classes, by anatomic level. Segmental injuries were recognised as a distinct entity. Associated injuries to the intraperitoneal abdomen, genitalia and perineum, pelvic ring, and upper limbs, which impact on clinical management and resources, were also accounted for. RESULTS: Between 1 November 2010 and 20 February 2011, 179 IED-related lower limb injuries in 103 consecutive casualties were classified, and their subsequent vascular and musculoskeletal treatment recorded. 69% of the injuries were traumatic amputations, and the remainder segmental injuries. 49% of casualties suffered bilateral lower limb amputation. The most common injury was class 3 (involving proximal lower leg or thigh, permitting effective above-knee tourniquet application, 49%), but more proximal patterns (class 4 or 5, preventing effective tourniquet application) accounted for 18% of injuries. Eleven casualties had associated intraperitoneal abdominal injuries, 41 suffered genital or perineal injuries, 9 had pelvic ring fractures, and 66 had upper limb injuries. The classification was easy to apply and correlated with management. CONCLUSIONS: The 'Bastion classification' is a pragmatic yet clinically relevant injury categorisation, which describes current injury patterns well, and should facilitate communication between clinicians, and the evaluation of interventions and outcomes. The validation cohort confirms that the injury burden from IEDs in the Helmand Province of Afghanistan remains high, with most casualties sustaining amputation through or above the knee. The rates of associated injury to the abdomen, perineum, pelvis and upper limbs are high. These findings have important implications for the training of military surgeons, staffing and resourcing of medical treatment facilities, to ensure an adequate skill mix to manage these complex and challenging injuries.

Pelagic to demersal transition in a coral-reef fish, the orbicular batfish Platax orbicularis.

Behavioural and ecological observations were made on young, reared Platax orbicularis in Opunohu Bay, Moorea, French Polynesia, during their transition from the pelagic, dispersive stage to the reef-orientated demersal stage. Seventy-two young P. orbicularis (17-75 mm standard length, LS ) were released in the pelagic zone and 20 (40-70 mm LS ) adjacent to the reefs. Swimming speed was slow (mean 5·2 cm s(-1) ) and independent of size. An ontogenetic descent was observed: the smallest P. orbicularis swam at the surface, medium-sized P. orbicularis swam in midwater (mean 5-13 m) and the largest P. orbicularis swam to the bottom, where many lay on their sides. Platax orbicularis swam southerly on average, away from the ocean and into the bay. Smaller P. orbicularis were more likely to swim directionally than larger individuals. Young P. orbicularis released near reef edges swam at similar, but more variable speeds (mean 6·6 cm s(-1) ). About half of those released near reefs swam away, but fewer swam away from an inshore fringing reef than from a patch reef near the bay mouth. Many P. orbicularis swam up the slope onto the reef top, but the little settlement observed was near the reef base. Average, near-reef swimming direction was also southerly. Some reef residents, in particular the triggerfish Balistapus undulatus, harassed young P. orbicularis.

ALK rearrangements in EBUS-derived transbronchial needle aspiration cytology in lung cancer.

OBJECTIVES: Patients with non-small cell lung cancer (NSCLC) positive for anaplastic lymphoma kinase (ALK) gene rearrangements may be treated successfully with the ALK inhibitor crizotinib. ALK copy-number abnormalities have also been described. In this study, we evaluated the suitability of fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) to determine ALK status in endobronchial ultrasound (EBUS)-derived cytology samples. METHODS: Samples were obtained from 55 consecutive patients with NSCLC who had undergone EBUS-transbronchial needle aspiration (TBNA) according to our standard clinical protocols. All tumours had been screened previously for epithelial growth factor receptor (EGFR) and v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations. FISH, using commercially available ALK rearrangement-specific probes, was employed to assess ALK status. IHC using the ALK-1 monoclonal antibody (DAKO) was also performed. RESULTS: FISH analysis was successful in 52 of 55 samples (94.5%); ALK rearrangement was demonstrated in 3 of 52 samples from patients with NSCLC (5.7%). ALK amplification was observed in 3 of 52 patient samples (5.7%) and an increase in ALK copy number was found in 28 of 52 patient samples (53.8%). IHC on cell blocks demonstrated ALK expression in one of three samples with ALK rearrangement. One patient sample had concomitant ALK rearrangement and KRAS mutation. CONCLUSIONS: We found FISH to be superior to IHC using the ALK-1 monoclonal antibody for the detection of ALK rearrangement in EBUS-TBNA cytology specimens in NSCLC, and also that ALK rearrangement can co-exist with KRAS mutation in the same tumour.

Development of an evidence-informed leisure time physical activity resource for adults with spinal cord injury: the SCI Get Fit Toolkit.

OBJECTIVES: To systematically develop an evidence-informed leisure time physical activity (LTPA) resource for adults with spinal cord injury (SCI). SETTING: Canada. METHODS: The Appraisal of Guidelines, Research and Evaluation (AGREE) II protocol was used to develop a toolkit to teach and encourage adults with SCI how to make smart and informed choices about being physically active. A multidisciplinary expert panel appraised the evidence and generated specific recommendations for the content of the toolkit. Pilot testing was conducted to refine the toolkit's presentation. RESULTS: Recommendations emanating from the consultation process were that the toolkit be a brief, evidence-based resource that contains images of adults with tetraplegia and paraplegia, and links to more detailed online information. The content of the toolkit should include the physical activity guidelines (PAGs) for adults with SCI, activities tailored to manual and power chair users, the benefits of LTPA, and strategies to overcome common LTPA barriers for adults with SCI. The inclusion of action plans and safety tips was also recommended. CONCLUSION: These recommendations have resulted in the development of an evidence-informed LTPA resource to assist adults with SCI in meeting the PAGs. This toolkit will have important implications for consumers, health care professionals and policy makers for encouraging LTPA in the SCI community.

A K(ATP) channel gene effect on sleep duration: from genome-wide association studies to function in Drosophila.

Humans sleep approximately a third of their lifetime. The observation that individuals with either long or short sleep duration show associations with metabolic syndrome and psychiatric disorders suggests that the length of sleep is adaptive. Although sleep duration can be influenced by photoperiod (season) and phase of entrainment (chronotype), human familial sleep disorders indicate that there is a strong genetic modulation of sleep. Therefore, we conducted high-density genome-wide association studies for sleep duration in seven European populations (N=4251). We identified an intronic variant (rs11046205; P=3.99 × 10(-8)) in the ABCC9 gene that explains ≈5% of the variation in sleep duration. An influence of season and chronotype on sleep duration was solely observed in the replication sample (N=5949). Meta-analysis of the associations found in a subgroup of the replication sample, chosen for season of entry and chronotype, together with the discovery results showed genome-wide significance. RNA interference knockdown experiments of the conserved ABCC9 homologue in Drosophila neurons renders flies sleepless during the first 3 h of the night. ABCC9 encodes an ATP-sensitive potassium channel subunit (SUR2), serving as a sensor of intracellular energy metabolism.

Integrating genetic studies of nicotine addiction into public health practice: stakeholder views on challenges, barriers and opportunities.

OBJECTIVE: Will emerging genetic research strengthen tobacco control programs? In this empirical study, we interview stakeholders in tobacco control to illuminate debates about the role of genomics in public health. METHODS: The authors performed open-ended interviews with 86 stakeholders from 5 areas of tobacco control: basic scientists, clinicians, tobacco prevention specialists, health payers, and pharmaceutical industry employees. Interviews were qualitatively analyzed using standard techniques. RESULTS: The central tension is between the hope that an expanding genomic knowledge base will improve prevention and smoking cessation therapies and the fear that genetic research might siphon resources away from traditional and proven public health programs. While showing strong support for traditional public health approaches to tobacco control, stakeholders recognize weaknesses, specifically the difficulty of countering the powerful voice of the tobacco industry when mounting public campaigns and the problem of individuals who are resistant to treatment and continue smoking. CONCLUSIONS: In order for genetic research to be effectively translated into efforts to minimize the harm of smoking-related disease, the views of key stakeholders must be voiced and disagreements reconciled. Effective translation requires honest evaluation of both the strengths and limitations of genetic approaches.