A social-ecological examination of sleep among Airmen in technical training.

Inadequate sleep is an on-going risk to the health and mission readiness of U.S. Armed Forces, with estimates of sleep problems high above U.S. civilian populations. Intervening early in the career of active duty Air Force personnel (or "Airmen") with education and the establishment of healthy behaviors may prevent short and long term-detriments of sleep problems. This paper describes the results of a qualitative study seeking to understand the facilitators and barriers to achieving good sleep in a technical training school during the first year of entry into the United States Air Force. Using the social ecological framework and content analysis, three focus groups with Airmen were conducted to explore themes at the individual, social, environmental, and organizational/policy level. Overall, results indicated a cohort motivated to achieve good sleep, and also struggling with a number of barriers across each level. This paper highlights opportunities for population health interventions during technical training aimed at supporting Airmen in developing healthy sleep behaviors early in the course of their career.

Reaching adults who smoke cigarettes in rural Appalachia: Rationale, design & analysis plan for a mixed-methods study disseminating pharmacy-delivered cessation treatment.

INTRODUCTION: Unlike other U.S. geographical regions, cigarette smoking prevalence remains stagnant in rural Appalachia. One avenue for reaching rural residents with evidence-based smoking cessation treatments could be utilizing community pharmacists. This paper describes the design, rationale, and analysis plan for a mixed-method study that will determine combinations of cessation treatment components that can be integrated within community pharmacies in rural Appalachia. The aim is to quantify the individual and synergistic effects of five highly disseminable and sustainable cessation components in a factorial experiment. METHODS: This sequential, mixed-method research design, based on the RE-AIM (Reach, Effectiveness, Adoption, Implementation, and Maintenance) framework, will use a randomized controlled trial with a 25 fully crossed factorial design (32 treatment combinations) to test, alone and in combination, the most effective evidence-based cessation components: (1) QuitAid (yes vs. no) (2) tobacco quit line (yes vs. no) (3) SmokefreeTXT (yes vs. no) (4) combination NRT lozenge + NRT patch (vs. NRT patch alone), and (5) eight weeks of NRT (vs. standard four weeks). RESULTS: Logistic regression will model abstinence at six-months, including indicators for the five treatment factors and all two-way interactions between the treatment factors. Demographic and smoking history variables will be considered to assess potential effect modification. Poisson regression will model quit attempts and percent of adherence to treatment components as secondary outcomes. CONCLUSION: This study will provide foundational evidence on how community pharmacies in medically underserved, rural regions can be leveraged to increase utilization of existing evidence-based tobacco cessation resources for treating tobacco dependence. CLINICAL TRIALS: NCT05660525.

Oro-Naso-Sino-Orbital-Cutaneous Fistula From Prolonged Cocaine Use.

Presentation We present the case of a 48-year-old man with nasal cellulitis and subsequent oro-naso-sino-orbital-cutaneous fistula from prolonged cocaine use. Diagnosis Initial laboratory investigations reported a raised white cell count (WBC) and C-Reactive Protein (CRP) and subsequently a positive atypical anti-neutrophil cytoplasm antibodies (ANCA) and positive anti-proteinase (PR3). Perihilar lung nodularity on chest imaging raised the possibility of a systemic autoimmune response. His urinalysis was positive for cocaine. Treatment He was commenced on Augmentin, Amphotericin B and Prednisolone. An obturator was created to manage the oro-nasal fistula. A subsequent naso-cutaneous defect was re-approximated. Daily nasal saline douche and abstinence of cocaine were recommended. Discussion Cocaine use in the community is rising and poses a challenge to multiple facets of our health care system.

Use of Tobacco for Weight Control across Products among Young Adults in the U.S. Military.

BACKGROUND: Approximately 17% of young adults currently use tobacco, most commonly cigarettes and/or electronic cigarettes (e-cigarettes), followed by other products (i.e., cigarillos, pipe/hookah, smokeless tobacco). Cigarettes have been historically used to control weight. Little is known about use of non-cigarette products for weight control, particularly among non-college young adults. Tobacco use in the military is higher than civilians, and personnel have increased motivation for weight control due to military fitness standards. This population might be vulnerable to use tobacco for this purpose. Purpose: Exploring prevalence, as well as demographic and behavioral correlates, of using tobacco products for weight control, among a large, diverse sample of military young adults. Methods: U.S. Air Force recruits (N = 24,543) completed a questionnaire about tobacco use. Among users of tobacco products, recruits reported if they had ever used that product to maintain their weight. Results: Smokeless tobacco was most commonly used for weight control (12.2%), followed by cigarettes (7.3%), e-cigarettes (5.5%), cigarillos (3.3%), and hookah/pipe (3.2%). Using tobacco for weight control was associated with fewer harm beliefs and more regular use of that product. Among e-cigarette users, having a higher BMI and a lower educational background was associated with ever using this product for weight control. Conclusions: The belief that a tobacco product helps control one's weight might increase the prevalence, and frequency of use, of that product among military young adults. Tobacco cessation programs should assess for this motivation of use and provide education about tobacco harm and alternative strategies for weight maintenance.

'I Think Smoking's the Same, but the Toys Have Changed.' Understanding Facilitators of E-Cigarette Use among Air Force Personnel.

BACKGROUND: The military has stringent anti-tobacco regulations for new recruits. While most tobacco products have declined in recent years, e-cigarette use has tripled among this population. However, little is known about the factors facilitating this inverse relationship. OBJECTIVES: Examine the facilitators of e-cigarette use during a high risk period following initial enlistment among young adults. METHODS: Focus groups were conducted with Airmen, Military Training Leaders (MTLs) and Technical Training Instructors (TTIs) to qualitatively explore unique characteristics of e-cigarettes leading to use in Technical Training. RESULTS: The most commonly used tobacco product across participants was cigarettes (42.7%), followed by e-cigarettes (28.0%) and smokeless tobacco (22.6%). Almost a third (28.7%) of participants reported using more than one tobacco product. E-cigarette use was much more common among Airmen (76.1%), compared to MTLs (10.9%) and TTIs (13.0%).Four main facilitators around e-cigarette use were identified including: 1) There is no reason not to use e-cigarettes; 2) Using e-cigarettes helps with emotion management; 3) Vaping is a way of fitting in; and 4) Existing tobacco control policies don't work for vaping. E-cigarettes were not perceived as harmful to self and others, which could explain why Airmen were much less likely to adhere to existing tobacco control regulations. Subversion was viewed as the healthy option compared to utilizing designated tobacco use areas due to the potential exposure to traditional tobacco smoke. This coupled with a lack of understanding about e-cigarette regulations and difficulties with enforcement, promoted use among this young adult population. CONCLUSION: Findings suggest that e-cigarettes are used for similar reasons as traditional tobacco products, but their unique ability to be concealed promotes their widespread use and circumvents existing tobacco control policies. In order to see reductions in use, environmental policies may need to be paired with behavioral interventions at the personal and interpersonal level.

Autosomal dominant tubulointerstitial kidney disease (ADTKD) in Ireland.

Introduction: Autosomal dominant tubulointerstitial kidney disease (ADTKD) is a rare genetic cause of renal impairment resulting from mutations in the MUC1, UMOD, HNF1B, REN, and SEC61A1 genes. Neither the national or global prevalence of these diseases has been determined. We aimed to establish a database of patients with ADTKD in Ireland and report the clinical and genetic characteristics of these families. Methods: We identified patients via the Irish Kidney Gene Project and referral to the national renal genetics clinic in Beaumont Hospital who met the clinical criteria for ADTKD (chronic kidney disease, bland urinary sediment, and autosomal dominant inheritance). Eligible patients were then invited to undergo genetic testing by a variety of methods including panel-based testing, whole exome sequencing and, in five families who met the criteria for diagnosis of ADTKD but were negative for causal genetic mutations, we analyzed urinary cell smears for the presence of MUC1fs protein. Results: We studied 54 individuals from 16 families. We identified mutations in the MUC1 gene in three families, UMOD in five families, HNF1beta in two families, and the presence of abnormal MUC1 protein in urine smears in three families (one of which was previously known to carry the genetic mutation). We were unable to identify a mutation in 4 families (3 of whom also tested negative for urinary MUC1fs). Conclusions: There are 4443 people with ESRD in Ireland, 24 of whom are members of the cohort described herein. We observe that ADTKD represents at least 0.54% of Irish ESRD patients.

High-throughput discovery of organic cages and catenanes using computational screening fused with robotic synthesis.

Supramolecular synthesis is a powerful strategy for assembling complex molecules, but to do this by targeted design is challenging. This is because multicomponent assembly reactions have the potential to form a wide variety of products. High-throughput screening can explore a broad synthetic space, but this is inefficient and inelegant when applied blindly. Here we fuse computation with robotic synthesis to create a hybrid discovery workflow for discovering new organic cage molecules, and by extension, other supramolecular systems. A total of 78 precursor combinations were investigated by computation and experiment, leading to 33 cages that were formed cleanly in one-pot syntheses. Comparison of calculations with experimental outcomes across this broad library shows that computation has the power to focus experiments, for example by identifying linkers that are less likely to be reliable for cage formation. Screening also led to the unplanned discovery of a new cage topology-doubly bridged, triply interlocked cage catenanes.

Alterations in circulating lymphoid cell populations in systemic small vessel vasculitis are non-specific manifestations of renal injury.

Innate lymphocyte populations, such as innate lymphoid cells (ILCs), γδ T cells, invariant natural killer T (iNK T) cells and mucosal-associated invariant T (MAIT) cells are emerging as important effectors of innate immunity and are involved in various inflammatory and autoimmune diseases. The aim of this study was to assess the frequencies and absolute numbers of innate lymphocytes as well as conventional lymphocytes and monocytes in peripheral blood from a cohort of anti-neutrophil cytoplasm autoantibody (ANCA)-associated vasculitis (AAV) patients. Thirty-eight AAV patients and 24 healthy and disease controls were included in the study. Patients with AAV were sampled both with and without immunosuppressive treatment, and in the setting of both active disease and remission. The frequencies of MAIT and ILC2 cells were significantly lower in patients with AAV and in the disease control group compared to healthy controls. These reductions in the AAV patients remained during remission. B cell count and frequencies were significantly lower in AAV in remission compared to patients with active disease and disease controls. Despite the strong T helper type 2 (Th) preponderance of eosinophilic granulomatosis with polyangiitis, we did not observe increased ILC2 frequency in this cohort of patients. The frequencies of other cell types were similar in all groups studied. Reductions in circulating ILC2 and MAIT cells reported previously in patients with AAV are not specific for AAV, but are more likely to be due to non-specific manifestations of renal impairment and chronic illness. Reduction in B cell numbers in AAV patients experiencing remission is probably therapy-related.

Chirality as a tool for function in porous organic cages.

The control of solid state assembly for porous organic cages is more challenging than for extended frameworks, such as metal-organic frameworks. Chiral recognition is one approach to achieving this control. Here we investigate chiral analogues of cages that were previously studied as racemates. We show that chiral cages can be produced directly from chiral precursors or by separating racemic cages by co-crystallisation with a second chiral cage, opening up a route to producing chiral cages from achiral precursors. These chiral cages can be cocrystallized in a modular, 'isoreticular' fashion, thus modifying porosity, although some chiral pairings require a specific solvent to direct the crystal into the desired packing mode. Certain cages are shown to interconvert chirality in solution, and the steric factors governing this behavior are explored both by experiment and by computational modelling.

Reticular synthesis of porous molecular 1D nanotubes and 3D networks.

Synthetic control over pore size and pore connectivity is the crowning achievement for porous metal-organic frameworks (MOFs). The same level of control has not been achieved for molecular crystals, which are not defined by strong, directional intermolecular coordination bonds. Hence, molecular crystallization is inherently less controllable than framework crystallization, and there are fewer examples of 'reticular synthesis', in which multiple building blocks can be assembled according to a common assembly motif. Here we apply a chiral recognition strategy to a new family of tubular covalent cages to create both 1D porous nanotubes and 3D diamondoid pillared porous networks. The diamondoid networks are analogous to MOFs prepared from tetrahedral metal nodes and linear ditopic organic linkers. The crystal structures can be rationalized by computational lattice-energy searches, which provide an in silico screening method to evaluate candidate molecular building blocks. These results are a blueprint for applying the 'node and strut' principles of reticular synthesis to molecular crystals.

EULAR/ERA-EDTA recommendations for the management of ANCA-associated vasculitis.

In this article, the 2009 European League Against Rheumatism (EULAR) recommendations for the management of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) have been updated. The 2009 recommendations were on the management of primary small and medium vessel vasculitis. The 2015 update has been developed by an international task force representing EULAR, the European Renal Association and the European Vasculitis Society (EUVAS). The recommendations are based upon evidence from systematic literature reviews, as well as expert opinion where appropriate. The evidence presented was discussed and summarised by the experts in the course of a consensus-finding and voting process. Levels of evidence and grades of recommendations were derived and levels of agreement (strengths of recommendations) determined. In addition to the voting by the task force members, the relevance of the recommendations was assessed by an online voting survey among members of EUVAS. Fifteen recommendations were developed, covering general aspects, such as attaining remission and the need for shared decision making between clinicians and patients. More specific items relate to starting immunosuppressive therapy in combination with glucocorticoids to induce remission, followed by a period of remission maintenance; for remission induction in life-threatening or organ-threatening AAV, cyclophosphamide and rituximab are considered to have similar efficacy; plasma exchange which is recommended, where licensed, in the setting of rapidly progressive renal failure or severe diffuse pulmonary haemorrhage. These recommendations are intended for use by healthcare professionals, doctors in specialist training, medical students, pharmaceutical industries and drug regulatory organisations.

Detecting and monitoring the symptoms of Parkinson's disease using smartphones: A pilot study.

BACKGROUND: Remote, non-invasive and objective tests that can be used to support expert diagnosis for Parkinson's disease (PD) are lacking. METHODS: Participants underwent baseline in-clinic assessments, including the Unified Parkinson's Disease Rating Scale (UPDRS), and were provided smartphones with an Android operating system that contained a smartphone application that assessed voice, posture, gait, finger tapping, and response time. Participants then took the smart phones home to perform the five tasks four times a day for a month. Once a week participants had a remote (telemedicine) visit with a Parkinson disease specialist in which a modified (excluding assessments of rigidity and balance) UPDRS performed. Using statistical analyses of the five tasks recorded using the smartphone from 10 individuals with PD and 10 controls, we sought to: (1) discriminate whether the participant had PD and (2) predict the modified motor portion of the UPDRS. RESULTS: Twenty participants performed an average of 2.7 tests per day (68.9% adherence) for the study duration (average of 34.4 days) in a home and community setting. The analyses of the five tasks differed between those with Parkinson disease and those without. In discriminating participants with PD from controls, the mean sensitivity was 96.2% (SD 2%) and mean specificity was 96.9% (SD 1.9%). The mean error in predicting the modified motor component of the UPDRS (range 11-34) was 1.26 UPDRS points (SD 0.16). CONCLUSION: Measuring PD symptoms via a smartphone is feasible and has potential value as a diagnostic support tool.

The role of the endothelium in systemic small vessel vasculitis.

The endothelium is the back-drop against which the effects set in train by interactions between Anti-Neutrophil Cytoplasm Antibodies (ANCA) and neutrophils are played out. This review considers the mechanisms of the endothelial cell injury that may result but also questions the impact of endothelial heterogeneity and endothelial cell activation in facilitation of vasculitic lesions, as well as the potential roles for endothelial-dependent anti-inflammatory mechanisms in controlling inflammation.

Technetium myocardial perfusion scanning in prerenal transplant evaluation in the United kingdom.

Because death with a functioning graft remains one of the most important causes of long-term renal transplant failure, cardiac risk stratification and screening for coronary artery disease are essential components of pretransplant assessment. Pretransplant screening for occult coronary artery disease in a subset of these patients may improve outcome. The UK follows the European Best practice guideline 1.5.5 E. Although echocardiography, thallium myocardial perfusion scanning (MPS), dobutamine stress echocardiography, and coronary angiography have been suggested as means of cardiovascular assessment, the best means of assessment remains undetermined. Therefore, we investigated the role of 99m technetium sestamibi myocardial perfusion scanning as an assessment tool for identifying those patients with end-stage renal failure at high risk of cardiovascular death after renal transplantation. Retrospectively, we studied 126 patients that had a MPS as part of their pretransplant assessment. Overall unadjusted survival was 65% at 3 years. Twelve deaths resulted from cardiovascular causes. A reversible defect on MPS was associated with a fatal cardiac event and all-cause mortality. The unadjusted hazard ratio of cardiac event with reversible defect on MPS was 3.1 (95% confidence interval, 1.1 to 18.2) and hazard ratio of death with reversible defect on MPS was 1.92 (95% confidence interval, 1.1 to 4.4). Thus, MPS may be a useful tool in cardiac risk stratification and in selecting patients with a favorable outcome after renal transplantation. Our patients with a reversible defect in particular have increased cardiac mortality. This group may benefit from coronary angiography.

Churg-Strauss syndrome and leukotriene antagonist use: a respiratory perspective.

BACKGROUND: Churg-Strauss syndrome (CSS) is a rare granulomatous small vessel vasculitis that occurs against a background of longstanding asthma. Leukotriene antagonists (LTAs) are used in the management of asthma and may facilitate a reduction in steroid dosage. Reports of the development of CSS in patients with asthma following the initiation of LTA therapy suggest either a causal association or an unmasking of latent CSS as steroid doses fall. We have undertaken a systematic review to establish whether evidence of a drug induced syndrome exists. METHODS: Systematic review searching Medline from database inception to August 2007 to identify cases with a possible association between LTAs and CSS. Hill's criteria of causation were used to assess strength of causality. RESULTS: 62 cases in which CSS developed after the introduction of LTA therapy were identified. Patients were divided into three groups: group 1 had received no previous steroid therapy; group 2 had been treated with oral and/or inhaled corticosteroids, but had no change in steroid therapy following LTA introduction; and group 3 had a clear reduction in steroid therapy following introduction of LTA therapy. The majority of patients from each group exhibited a clear temporal relationship between initiation of LTA and development of CSS, with no evidence of pre-existing disease. CONCLUSIONS: Currently available evidence suggests an association between LTA and CSS that may be causal.

Current and future therapy of small vessel vasculitis of the kidney.

Renal involvement, characterised histologically by crescentic glomerulonephritis, is the most potent clinical determinant of long-term outcome in ANCA-associated systemic vasculitis (AASV). The presence of autoantibodies against neutrophil granule constituents may be an important pathogenic factor. The duration and intensity of treatment of renal vasculitis with standard induction therapies (prednisolone and cyclophosphamide) have been clarified by the completion of a number of prospective clinical trials. Based on these, most patients with renal vasculitis should receive 3 months of pulsed intravenous or oral cyclophosphamide plus tailing doses of prednisolone, with switching to azathioprine plus prednisolone thereafter for a minimum of 2 years. Added to this therapeutic backbone are methotrexate, plasma exchange and mycophenolate mofetil, use of which has been addressed by further prospective trials, most of which have been conducted by the European Vasculitis Study Group. Additional therapies, such as intravenous immunoglobulin and antithymocyte globulin may be used in cases of resistant vasculitis and when cyclophosphamide is poorly tolerated. Newer biologic agents are now emerging and are being subjected to rigorous testing. Of these, monoclonal antibodies directed against TNFa (a central cytokine in AASV pathogenesis) and CD20 (a specific B-cell marker) are proving most promising. This review will put these various therapeutic approaches into the context of renal vasculitis, with emphasis on a practical approach to management.

Testing the assumptions of linear prediction analysis in normal vowels.

In this paper we develop an improved surrogate data test to show experimental evidence, for all the simple vowels of U.S. English, for both male and female speakers, that Gaussian linear prediction analysis, a ubiquitous technique in current speech technologies, cannot be used to extract all the dynamical structure of real speech time series. The test provides robust evidence undermining the validity of these linear techniques, supporting the assumptions of either dynamical nonlinearity and/or non-Gaussianity common to more recent, complex, efforts at dynamical modeling speech time series. However, an additional finding is that the classical assumptions cannot be ruled out entirely, and plausible evidence is given to explain the success of the linear Gaussian theory as a weak approximation to the true, nonlinear/non-Gaussian dynamics. This supports the use of appropriate hybrid linear/nonlinear/non-Gaussian modeling. With a calibrated calculation of statistic and particular choice of experimental protocol, some of the known systematic problems of the method of surrogate data testing are circumvented to obtain results to support the conclusions to a high level of significance.

Severity of primary MPGN, rather than MPGN type, determines renal survival and post-transplantation recurrence risk.

Previous studies suggested that membranoproliferative glomerulonephritis (MPGN) type II has a worse renal survival and an unacceptable risk of recurrence post transplantation. We hypothesised that other factors may determine this risk. We analysed all cases (n=70) of MPGN diagnosed by renal biopsy in Ireland from 1972 to 1995. We used Cox regression analysis to determine factors that were independently predictive of renal failure. MPGN II had more crescent formation and mesangial proliferation (P<0.05). Mean follow-up duration was 13.8 years, during which time 41 (58.6%) developed end-stage renal failure (ESRF). The median time to ESRF was 8.3 years (95% confidence interval 5.7-10.9) and 5-, 10-, and 20-year probabilities of ESRF were 32, 54, and 70%, respectively. Multivariate analysis revealed that severity of interstitial fibrosis (P<0.05), crescent formation (P<0. 01) and mesangial proliferation (P<0.05) were independently associated with ESRF. Decade of diagnosis, age, MPGN type, and creatinine or complement level at baseline did not predict renal survival in this model. In 21 (49%) of the 43 renal transplants, MPGN recurred. Younger age at initial diagnosis (P<0.01) and the presence of crescents on the original biopsy (P<0.005) were independently associated with recurrence on multivariate analysis. MPGN type was not associated with recurrence in this model. Contrary to previous reports, after controlling for crescent formation, MPGN II was not associated with more ESRF or recurrence in the allograft. It is therefore the more aggressive glomerular changes associated with MPGN II, rather than the disease type per se, that determine outcome.

Intravital microscopy in the study of ANCA-associated systemic vasculitis.

In addition to being useful clinical markers of systemic vasculitis, anti-neutrophil cytoplasm antibodies (ANCA) may play a role in the initiation of vasculitic injury. These autoantibodies can induce neutrophil degranulation, dysregulated neutrophil apoptosis and neutrophil adhesion to endothelium in static cellular systems. This mini-review will place these sentinel findings in the context of more recent studies using the parallel plate flow chamber and novel animal models of ANCA-associated vasculitis (AASV). Rodent models lend themselves well to investigation of leukocyte endothelial interaction using intravital microscopy. In this way, one can study ANCA-induced leukocyte adhesion/transmigration, and microvascular injury in real time. These studies may then be extended to look at the impact of novel therapeutic agents on these processes.

Short-chain acyl-CoA dehydrogenase deficiency associated with early onset severe axonal neuropathy.

Two unusual cases of axonal neuropathy associated with short-chain acyl-CoA dehydrogenase (SCAD) deficiency are described. These two unrelated infants presented with profound generalised weakness, particularly affecting the upper limbs. Clinical examination revealed generalised peripheral hypotonia and weakness, with absent deep tendon reflexes. An axonal polyneuropathy was confirmed on electromyogram (EMG) and nerve conduction studies (NCS) and, following an extensive metabolic screen, an acylcarnitine and organic acid profile consistent with a short-chain fatty acid beta-oxidation defect was found. In both cases, SCAD deficiency was confirmed by enzyme analysis. Genetic analysis showed the presence of common gene variations in the SCAD gene. SCAD deficiency is a rare disorder with a wide clinical phenotype. SCAD deficiency associated with axonal neuropathy has not previously been reported. As highlighted in these cases, it may be necessary to include axonal neuropathy as a presenting feature of SCAD.