Complications of fibrotic interstitial lung disease for the general radiologist.

Interstitial lung diseases (ILDs) are a heterogeneous group of conditions characterised by non-infective inflammation and scarring of the lung parenchyma. They are not infrequently encountered by the general radiologist in both acute and outpatient reporting settings who may even be the first to make the diagnosis. In the acute setting, patients with ILD can present with respiratory deterioration due to a number of causes and in addition to the common causes of dyspnoea, an acute exacerbation of ILD needs to be considered. An exacerbation can be initiated by common triggers such as infection, pulmonary embolism (PE), and heart failure, and it can also be initiated by an insult to the lung or occur due to an unknown cause. Particular care needs to be taken when interpreting computed tomography (CT) examinations in these patients as the findings of an acute exacerbation are non-specific and patient and technical factors can cause spurious appearances including dependent changes, breathing artefact and contrast medium opacification. In the non-acute setting, patients with ILD are at increased risk of lung cancer and pulmonary hypertension (PH), with lung cancer being a particularly important consideration as treatments carry the risk of triggering an acute exacerbation or deterioration in lung function. Overall, this review aims to provide an overview for the general radiologist of additional factors to consider when interpreting scans in patients with ILD and how the presence of ILD impacts the differential diagnoses and complications that can occur in these patients in both acute and non-acute settings.

Modeling and comparing the distributions and associations of two co-occurring catshark species off South Africa.

Holohalaelurus regani and Scyliorhinus capensis are relatively small catsharks, which both occur off the continental shelf around South Africa and are often caught together as by-catch in demersal trawls. The present study used data collected during annual demersal research surveys conducted between 2009 and 2015 and is a first attempt at modeling the potential intra- and interspecific associations, by maturity stage and depth, of H. regani and S. capensis to elucidate species-specific patterns in their distributions in South African waters. Intraspecifically, both species displayed a wide overlap in distribution between maturity stages, but only H. regani displayed marked changes in distribution with maturity stage, with mature individuals found further eastwards and occupying deeper waters than immature individuals. Interspecifically, the two catsharks displayed an inverse relationship in their distribution, with an increase in the abundance of H. regani and a decrease in the abundance of S. capensis when moving from the south coast to the west coast. Some localized patches of co-occurrence were, however, evident between species and maturity stages, especially in offshore areas. Overall, our results indicated a stronger co-occurrence of mature and immature stages within each species and a rather weak co-occurrence of maturity stages between the two species. The spatial information provided in the present study provides useful information on how sharks with similar morphologies and lifestyles may partition their habitat as a mechanism for potentially reducing competition between them.

Adaptation to hypoxic environments; bearded gobies Sufflogobius bibarbatus in the Benguela upwelling ecosystem.

The oceans of the world are slowly losing oxygen, in part because of climate change and in part because of anthropogenic eutrophication. This deoxygenation affects marine organisms in species-specific ways. This paper reviews what is known on how hypoxia tolerant species respond to low dissolved oxygen, using the bearded goby Sufflogobius bibarbatus as a model system. This species is endemic to the Benguela upwelling ecosystem, where, off Namibia, 9000 km2 of the shelf is hypoxic. Here, the species is now considered central to ecosystem functioning and in recent decades it has sustained commercial fisheries. Unlike their predators, S. bibarbatus has strong anti-predator responses as they can remain alert and escape threats in anoxic and severely hypoxic waters and can cope with sulphide shocks. Populations display diel vertical migration and shuttle between suboxic seabed refugia during the day to more oxygenated waters higher up in the water column at night and whilst they may share the water column with predators they may reduce their predation risk by associating with jellyfish (Aequorea forskalea and Chrysaora fulgida). The spatial distribution of S. bibarbatus varies with changes in available oxygen and populations expand and contract with climate-induced changes in the distribution of hypoxic waters. This species has an unusual diet and plays an important role in ecosystem functioning. It is a batch-spawner, with a protracted spawning season. Remarkably, males display alternative reproductive tactics and reproduction can take place at oxygen levels <0·5 ml l-1 dissolved oxygen on the shelf break. Gaps in knowledge are identified and future works are proposed.

A Health Services Research Agenda for Bariatric Surgery Within the Veterans Health Administration.

In 2016, the Veterans Health Administration (VHA) held a Weight Management State of the Art conference to identify evidence gaps and develop a research agenda for population-based weight management for veterans. Included were behavioral, pharmacologic, and bariatric surgery workgroups. This article summarizes the bariatric surgery workgroup (BSWG) findings and recommendations for future research. The BSWG agreed that there is evidence from randomized trials and large observational studies suggesting that bariatric surgery is superior to medical therapy for short- and intermediate-term remission of type 2 diabetes, long-term weight loss, and long-term survival. Priority evidence gaps include long-term comorbidity remission, mental health, substance abuse, and health care costs. Evidence of the role of endoscopic weight loss options is also lacking. The BSWG also noted the limited evidence regarding optimal timing for bariatric surgery referral, barriers to bariatric surgery itself, and management of high-risk bariatric surgery patients. Clinical trials of pre- and post-surgery interventions may help to optimize patient outcomes. A registry of overweight and obese veterans and a workforce assessment to determine the VHA's capacity to increase bariatric surgery access were recommended. These will help inform policy modifications and focus the research agenda to improve the ability of the VHA to deliver population-based weight management.

TPM3 deletions cause a hypercontractile congenital muscle stiffness phenotype.

OBJECTIVE: Mutations in TPM3, encoding Tpm3.12, cause a clinically and histopathologically diverse group of myopathies characterized by muscle weakness. We report two patients with novel de novo Tpm3.12 single glutamic acid deletions at positions ΔE218 and ΔE224, resulting in a significant hypercontractile phenotype with congenital muscle stiffness, rather than weakness, and respiratory failure in one patient. METHODS: The effect of the Tpm3.12 deletions on the contractile properties in dissected patient myofibers was measured. We used quantitative in vitro motility assay to measure Ca(2+) sensitivity of thin filaments reconstituted with recombinant Tpm3.12 ΔE218 and ΔE224. RESULTS: Contractility studies on permeabilized myofibers demonstrated reduced maximal active tension from both patients with increased Ca(2+) sensitivity and altered cross-bridge cycling kinetics in ΔE224 fibers. In vitro motility studies showed a two-fold increase in Ca(2+) sensitivity of the fraction of filaments motile and the filament sliding velocity concentrations for both mutations. INTERPRETATION: These data indicate that Tpm3.12 deletions ΔE218 and ΔE224 result in increased Ca(2+) sensitivity of the troponin-tropomyosin complex, resulting in abnormally active interaction of the actin and myosin complex. Both mutations are located in the charged motifs of the actin-binding residues of tropomyosin 3, thus disrupting the electrostatic interactions that facilitate accurate tropomyosin binding with actin necessary to prevent the on-state. The mutations destabilize the off-state and result in excessively sensitized excitation-contraction coupling of the contractile apparatus. This work expands the phenotypic spectrum of TPM3-related disease and provides insights into the pathophysiological mechanisms of the actin-tropomyosin complex.

Three-dimensional imaging of shear bands in bulk metallic glass composites.

The mechanism of the increase in ductility in bulk metallic glass matrix composites over monolithic bulk metallic glasses is to date little understood, primarily because the interplay between dislocations in the crystalline phase and shear bands in the glass could neither be imaged nor modelled in a validated way. To overcome this roadblock, we show that shear bands can be imaged in three dimensions by atom probe tomography from density variations in the reconstructed atomic density, which density-functional theory suggests being a local-work function effect. Imaging of near-interface shear bands in Ti48 Zr20 V12 Cu5 Be15 bulk metallic glass matrix composite permits measurement of their composition, thickness, branching and interactions with the dendrite interface. These results confirm that shear bands here nucleate from stress concentrations in the glass due to intense, localized plastic deformation in the dendrites rather than intrinsic structural inhomogeneities.

The evolution of respect for property.

Although possession is 'nine-tenths of the law', respect for ownership is widespread in the animal kingdom even without third-party enforcement. Thus, the first individuals to find objects are frequently left unchallenged by potential competitors and tend to win contests when disputes arise. Game theory has shown that respect for ownership ('Bourgeois' behaviour) can arise as an arbitrary convention to avoid costly disputes. However, the same theory predicts that a paradoxical respect for lack of ownership ('anti-Bourgeois' behaviour) can evolve under the same conditions and in some cases is the only stable outcome. Despite these predictions, anti-Bourgeois behaviour is rare in nature, whereas respect for ownership is frequently not absolute. Here, we review extensions of the classic models involving repeated interactions, confusion over roles, strategic coordination of behaviour ('secret handshakes'), owner-intruder asymmetries and continuous control of fighting investment. Confusion over roles and owner-intruder asymmetries in fighting ability may explain why respect for ownership is often partial. Moreover, although most model extensions facilitate the evolution of Bourgeois-like behaviour, secret handshakes and continuous control of fighting investment render the alternative anti-Bourgeois convention unstable. We develop these insights to highlight several key areas for future investigation.

Challenges to delivery of isoniazid preventive therapy in a cohort of children exposed to tuberculosis in Timor-Leste.

OBJECTIVES: To evaluate the number and geographic location of children aged <5 years exposed to sputum smear-positive tuberculosis (TB) in Timor-Leste, to determine the proportion evaluated for isoniazid preventive therapy (IPT) and to review the programmatic challenges present in delivering IPT to this cohort. METHODS: A total of 256 consecutive sputum smear-positive TB index cases diagnosed at Bairo Pite Clinic between August 2013 and July 2014 were interviewed about places of residence and household contacts <5 years of age in the 3 months preceding diagnosis. Attendance of these contacts for screening and the outcome of screening were recorded prospectively. RESULTS: The majority (225 of 256, 88%) of index cases resided in Dili, but 73 of 225 (32%) of these also had a second address outside the capital. A total of 255 contacts were identified; 172 of 255 (67%) of whom lived in Dili district and 83 of 255 (33%) of whom resided in remote districts. Only 66 of 255 (26%) contacts attended for evaluation for IPT, of whom 46 of 255 (18%) started IPT and nine of 255 (3.5%) were diagnosed with TB. Attendance was significantly less likely when the index case was not the parent of the child contact. CONCLUSIONS: Sputum smear-positive pulmonary TB cases frequently result in household exposure of children <5 years in Timor-Leste, and provision of IPT is suboptimal. Contacts are located in diverse and distant locations. Further studies to delineate access barriers to IPT and review programmatic models that will facilitate IPT scale up in Timor-Leste are needed.

Methodology for a community-based stroke preparedness intervention: the Acute Stroke Program of Interventions Addressing Racial and Ethnic Disparities Study.

BACKGROUND AND PURPOSE: Acute stroke education has focused on stroke symptom recognition. Lack of education about stroke preparedness and appropriate actions may prevent people from seeking immediate care. Few interventions have rigorously evaluated preparedness strategies in multiethnic community settings. METHODS: The Acute Stroke Program of Interventions Addressing Racial and Ethnic Disparities (ASPIRE) project is a multilevel program using a community-engaged approach to stroke preparedness targeted to underserved black communities in the District of Columbia. This intervention aimed to decrease acute stroke presentation times and increase intravenous tissue-type plasminogen activator utilization for acute ischemic stroke. RESULTS: Phase 1 included (1) enhancement of focus of emergency medical services on acute stroke; (2) hospital collaborations to implement and enrich acute stroke protocols and transition District of Columbia hospitals toward primary stroke center certification; and (3) preintervention acute stroke patient data collection in all 7 acute care District of Columbia hospitals. A community advisory committee, focus groups, and surveys identified perceptions of barriers to emergency stroke care. Phase 2 included a pilot intervention and subsequent citywide intervention rollout. A total of 531 community interventions were conducted, reaching >10,256 participants; 3289 intervention evaluations were performed, and 19,000 preparedness bracelets and 14,000 stroke warning magnets were distributed. Phase 3 included an evaluation of emergency medical services and hospital processes for acute stroke care and a year-long postintervention acute stroke data collection period to assess changes in intravenous tissue-type plasminogen utilization. CONCLUSIONS: We report the methods, feasibility, and preintervention data collection efforts of the ASPIRE intervention. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT00724555.

Water droplet evaporation in varied gravity and electric fields.

Sessile water droplet evaporation in varied gravity and electric fields has been experimentally studied. Specifically, the influences of gravity and electric fields are investigated in the context of the heat flux distribution beneath the droplets, as well as the droplet mechanics and resulting shapes. Experimental testing was carried out during a European Space Agency (ESA) Parabolic Flight Campaign (PFC 66). The droplets tested evaporated with a pinned contact line, a single wettability condition, and varied droplet volume and substrate heat flux. The peak heat transfer was located at the contact line for all cases. The peak heat flux, average heat flux, and droplet evaporation rate were shown to vary strongly with gravity, with higher values noted for hypergravity conditions and lower values in microgravity conditions. The droplet thermal inertia was shown to play a significant role, with larger droplets taking more time to reach thermal equilibrium during the parabolic testing period. No significant impact of the electric field on the droplet evaporation was noted for these test conditions.

Association of chronic kidney disease with cerebral microbleeds in patients with primary intracerebral hemorrhage.

BACKGROUND AND PURPOSE: To investigate the relationship between chronic kidney disease (CKD) and MRI-defined cerebral microbleeds (CMB), a harbinger of future intracerebral hemorrhage (ICH), among patients with a recent history of primary ICH. METHODS: Using data from a predominantly black cohort of patients with a recent ICH-enrolled in an observational study between September 2007 and June 2011, we evaluated the association between CKD (defined as estimated low glomerular filtration rate<60 mL/min per 1.73 m(2)) and CMB on gradient-echo MRI. Multivariable models were generated to determine the contribution of CKD to the presence, number, and location of CMB. RESULTS: Of 197 subjects with imaging data, mean age was 59 years, 48% were women, 73% were black, 114 (58%) had ≥1 CMBs, and 52 (26%) had CKD. Overall, CKD was associated with presence of CMB (adjusted odds ratio, 2.70; 95% confidence interval [CI], 1.10-6.59) and number of CMB (adjusted relative risk, 2.04; 95% CI, 1.27-3.27). CKD was associated with CMB presence (adjusted odds ratio, 3.44; 95% CI, 1.64-7.24) and number (adjusted relative risk, 2.46; 95% CI, 1.11-5.42) in black patients, but not CMB presence (adjusted odds ratio, 3.00; 95% CI, 0.61-14.86) or number (adjusted relative risk, 1.03; 95% CI: 0.22-4.89) in non-Hispanic white patients (interactions by race were statistically not significant). CONCLUSIONS: CKD is associated with a greater presence and number of CMB in ICH patients, particularly in patients of black race. Future studies should assess whether low estimated glomerular filtration rate may be a CMB risk marker or potential therapeutic target for mitigating the development of CMB.

Predictors of highly prevalent brain ischemia in intracerebral hemorrhage.

OBJECTIVE: This study was undertaken to determine the prevalence, characteristics, risk factors, and temporal profile of concurrent ischemic lesions in patients with acute primary intracerebral hemorrhage (ICH). METHODS: Patients were recruited within a prospective, longitudinal, magnetic resonance imaging (MRI)-based study of primary ICH. Clinical, demographic, and MRI data were collected on all subjects at baseline and 1 month. RESULTS: Of the 138 patients enrolled, mean age was 59 years, 54% were male, 73% were black, and 84% had a history of hypertension. At baseline, ischemic lesions on diffusion-weighted imaging (DWI) were found in 35% of patients. At 1 month, lesions were present in 27%, and of these lesions, 83% were new and not present at baseline. ICH volume (p = 0.025), intraventricular hemorrhage (p = 0.019), presence of microbleeds (p = 0.024), and large, early reductions in mean arterial pressure (p = 0.003) were independent predictors of baseline DWI lesions. A multivariate logistical model predicting the presence of 1-month DWI lesions included history of any prior stroke (p = 0.012), presence of 1 or more microbleeds (p = 0.04), black race (p = 0.641), and presence of a DWI lesion at baseline (p = 0.007). INTERPRETATION: This study demonstrates that >⅓ of patients with primary ICH have active cerebral ischemia at baseline remote from the index hematoma, and » of patients experience ongoing, acute ischemic events at 1 month. Multivariate analyses implicate blood pressure reductions in the setting of an active vasculopathy as a potential underlying mechanism. Further studies are needed to determine the impact of these lesions on outcome and optimal management strategies to arrest vascular damage.

Intraosseous schwannoma in schwannomatosis.

This study investigates the clinical, radiological, and pathological features of two cases of intraosseous schwannoma that arose in patients with multiple soft tissue schwannomas. In both cases, the patients were adult females and the tibial bone was affected. Vestibular schwannomas were not identified, indicating that these were not cases of neurofibromatosis 2 (NF2). Radiographs showed a well-defined lytic lesion in the proximal tibia; in one case, this was associated with a pathological fracture. Histologically, both cases showed typical features of benign schwannoma. Molecular analysis of one of the excised tumors showed different alterations in the NF2 gene in keeping with a diagnosis of schwannomatosis. Our findings show for the first time that intraosseous schwannomas can occur in schwannomatosis.

An encyclopedia of mouse genes.

The laboratory mouse is the premier model system for studies of mammalian development due to the powerful classical genetic analysis possible (see also the Jackson Laboratory web site, http://www.jax.org/) and the ever-expanding collection of molecular tools. To enhance the utility of the mouse system, we initiated a program to generate a large database of expressed sequence tags (ESTs) that can provide rapid access to genes. Of particular significance was the possibility that cDNA libraries could be prepared from very early stages of development, a situation unrealized in human EST projects. We report here the development of a comprehensive database of ESTs for the mouse. The project, initiated in March 1996, has focused on 5' end sequences from directionally cloned, oligo-dT primed cDNA libraries. As of 23 October 1998, 352,040 sequences had been generated, annotated and deposited in dbEST, where they comprised 93% of the total ESTs available for mouse. EST data are versatile and have been applied to gene identification, comparative sequence analysis, comparative gene mapping and candidate disease gene identification, genome sequence annotation, microarray development and the development of gene-based map resources.

An insight into the reproductive biology of the bearded goby Sufflogobius bibarbatus.

Preliminary results obtained from histological analyses of the male reproductive organs, supplemented with field and behavioural data, indicate that Sufflogobius bibarbatus, a small, slow growing gobiid exhibiting low fecundity, which plays an important role in the food web off Namibia, where large areas of the shelf are hypoxic, spawns demersally. Large males defend benthic nests, possibly at the edge of the hypoxic shelf. Male reproductive strategy appears to be flexible, and tentative evidence to suggest that polygyny and sneaking may also occur is presented.

Anxiety in a Specialist Perinatal Mental Health Service: patient characteristics, management, and outcomes.

OBJECTIVES: To outline characteristics of patients with anxiety diagnoses attending a Specialist Perinatal Mental Health Service (SPMHS) in Ireland, the mental health care received by those patients, mental health and obstetric outcomes for those patients, and immediate neonatal outcomes for their babies. METHODS: A retrospective chart review was conducted of patients with antenatal anxiety diagnoses who attended the SPMHS in University Maternity Hospital Limerick, from initiation of the service to the end of its first year. RESULTS: Data were collected on 100 patients, 81 with a mental health diagnosis prior to attending the SPMHS, 32 with prior engagement with psychiatry, and 23 with a previous perinatal diagnosis. The mean age of patients was 32.4 (19-47, std 6.158). Beyond initial assessment, the Mental Health Midwife was involved in the care of 61% of patients, more than any other specialty including psychiatry. Twenty-seven patients had psychiatric medication either started or altered by the SPMHS. The most common reason for eventual discharge was that patients were well. Two patients presented in mental-health-related crisis to emergency services and one patient was admitted to an acute psychiatric ward. CONCLUSIONS: Patients attending the SPMHS for anxiety spanned a broad spectrum of demographics and diagnoses and received varied set of interventions. A significant proportion of patients had a primary diagnosis of Pregnancy-related anxiety. The Mental Health Midwife played a key role in management of these patients. Though rates of mental health crises and admissions were low, the absence of a Mother and Baby Unit in Ireland was highlighted.

Poor long-term blood pressure control after intracerebral hemorrhage.

BACKGROUND AND PURPOSE: Hypertension is the most important risk factor associated with intracerebral hemorrhage. We explored racial differences in blood pressure (BP) control after intracerebral hemorrhage and assessed predictors of BP control at presentation, 30 days, and 1 year in a prospective cohort study. METHODS: Subjects with spontaneous intracerebral hemorrhage were identified from the DiffErenCes in the Imaging of Primary Hemorrhage based on Ethnicity or Race (DECIPHER) Project. BP was compared by race at each time point. Multivariable linear regression was used to determine predictors of presenting mean arterial pressure, and longitudinal linear regression was used to assess predictors of mean arterial pressure at follow-up. RESULTS: A total of 162 patients were included (mean age, 59 years; 53% male; 77% black). Mean arterial pressure at presentation was 9.6 mm Hg higher in blacks than whites despite adjustment for confounders (P=0.065). Fewer than 20% of patients had normal BP (<120/80 mm Hg) at 30 days or 1 year. Although there was no difference at 30 days (P=0.331), blacks were more likely than whites to have Stage I/II hypertension at 1 year (P=0.036). Factors associated with lower mean arterial pressure at follow-up in multivariable analysis were being married at baseline (P=0.032) and living in a facility (versus personal residence) at the time of BP measurement (P=0.023). CONCLUSIONS: Long-term BP control is inadequate in patients after intracerebral hemorrhage, particularly in blacks. Further studies are needed to understand the role of social support and barriers to control to identify optimal approaches to improve BP in this high-risk population.

Racial disparities in tissue plasminogen activator treatment rate for stroke: a population-based study.

BACKGROUND AND PURPOSE: Some prior studies have shown that racial disparities exist in intravenous tissue plasminogen activator (tPA) use for acute ischemic stroke. We sought to determine whether race was associated with tPA treatment for stroke in a predominantly black urban population. METHODS: Systematic chart abstraction was performed on consecutive hospitalized patients with ischemic stroke from all 7 acute care hospitals in the District of Columbia from February 1, 2008, to January 31, 2009. RESULTS: Of 1044 patients with ischemic stroke, 74% were black, 19% non-Hispanic white, and 5% received intravenous tPA. Blacks were one third less likely than whites to receive intravenous tPA (3% versus 10%, P<0.001). However, blacks were also less likely than whites to present within 3 hours of symptom onset (13% versus 21%, P=0.004) and also less likely to be tPA-eligible (5% versus 13%, P<0.001). Of those who presented within 3 hours, blacks were almost half as likely to be treated with intravenous tPA than whites (27% versus 46%, P=0.023). The treatment rate for tPA-eligible patients was similar for blacks and whites (70% versus 76%, P=0.62). CONCLUSIONS: In this predominantly black urban population hospitalized for acute ischemic stroke, blacks were significantly less likely to be treated with intravenous tPA due to contraindications to treatment, delayed presentation, and stroke severity. Effective interventions designed to increase treatment in this population need to focus on culturally relevant education programs designed to address barriers specific to this population.

Understanding reasons for delay in seeking acute stroke care in an underserved urban population.

BACKGROUND AND PURPOSE: Few patients arrive early enough at hospitals to be eligible for emergent stroke treatment. There may be barriers specific to underserved, urban populations that need to be identified before effective educational interventions to reduce delay times can be developed. METHODS: A survey of respondents' likely action in a hypothetical stroke situation was given to 253 community volunteers in the catchment areas of a large urban community hospital. Concurrently, 100 structured interviews were conducted in the same hospital with patients with acute stroke or a proxy. RESULTS: In this predominantly urban, black population, if faced with a hypothetical stroke, 89% of community volunteers surveyed said they would call 911 first, and few felt any of the suggested potential barriers applied to them. However, only 12% of patients with stroke interviewed actually called 911 first (OR, 63.9; 95% CI, 29.5 to 138.2). Instead, 75% called a relative/friend. Eighty-nine percent of patients with stroke reported significant delay in seeking medical attention, and almost half said the reason for the delay was thinking the symptoms were not serious and/or they would self-resolve. For those arriving by ambulance, only 25% did so because they thought it would be faster, whereas 35% cited having no other transportation options. CONCLUSIONS: In this predominantly black urban population, although 89% of community volunteers report the intent of calling 911 during a stroke, only 12% of actual patients with stroke did so. Further research is needed to determine and conquer the barriers between behavioral intent and actual behavior to call 911 for witnessed stroke.