Energy- and flux-budget (EFB) turbulence closure model for the stably stratified flows. Part I: Steady-state, homogeneous regimes

We propose a new turbulence closure model based on the budget equations for the key second moments: turbulent kinetic and potential energies: TKE and TPE (comprising the turbulent total energy: TTE = TKE + TPE) and vertical turbulent fluxes of momentum and buoyancy (proportional to potential temperature). Besides the concept of TTE, we take into account the non-gradient correction to the traditional buoyancy flux formulation. The proposed model grants the existence of turbulence at any gradient Richardson number, Ri. Instead of its critical value separating - as usually assumed - the turbulent and the laminar regimes, it reveals a transition interval, 0.1< Ri <1, which separates two regimes of essentially different nature but both turbulent: strong turbulence at Ri<<1; and weak turbulence, capable of transporting momentum but much less efficient in transporting heat, at Ri>1. Predictions from this model are consistent with available data from atmospheric and lab experiments, direct numerical simulation (DNS) and large-eddy simulation (LES).Comment: 40 pages, 6 figures, Boundary-layer Meteorology, resubmitted, revised versio

Treatment efficacy in a soman-poisoned guinea pig model: added value of physostigmine?

Current treatment of organophosphate poisoning is insufficient, and survivors may suffer from long-lasting adverse effects, such as cognitive deficits and sleep-wake disturbances. In the present study, we aimed at developing a guinea pig model to investigate the benefits of immediate and delayed stand-alone therapy on the development of clinical signs, EEG, heart rate, respiration and AChE activity in blood and brain after soman poisoning. The model allowed the determination of the therapeutic effects at the short-term of obidoxime, atropine and physostigmine. Obidoxime exerted the highest therapeutic efficacy at administration of the lowest dose (3.1 mg/kg i.m.), whereas two higher doses (9 and 18 mg/kg) were less effective on most parameters. Addition of atropine at 0.03 and 3 mg/kg (i.m.) to the treatment did not improve the therapeutic effects of obidoxime alone. Physostigmine (0.8 mg/kg im) at 1 min after poisoning increased mortality. Two lower doses (0.1 and 0.3 mg/kg i.m.) showed improvements on all parameters but respiration. The middle dose was most effective in preventing seizure development and therefore assessed as the most efficacious dose. Combined treatment of obidoxime and physostigmine shortened the duration of seizures, if present, from up to 80 min to ~10–15 min. In practice, treatment will be employed when toxic signs appear, with the presence of high levels of AChE inhibition in both blood and brain. Administration of physostigmine at that moment showed to be redundant or even harmful. Therefore, treatment of OP poisoning with a carbamate, such as physostigmine, should be carefully re-evaluated

Pregnancy in multiple system atrophy: a case report

<p>Abstract</p> <p>Introduction</p> <p>Multiple system atrophy is a late, adult-onset α-synucleinopathy with no data on the effect of pregnancy on the disease course. Early stage multiple system atrophy can be difficult to distinguish from Parkinson's disease.</p> <p>Case presentation</p> <p>We describe the case of an Irish woman with parkinsonism starting at age 31, initially diagnosed as having dopa-responsive, idiopathic Parkinson's disease, who successfully delivered a full-term child at age 35. Her pregnancy was complicated by severe orthostatic hypotension and motor fluctuations. Two years post-partum, she underwent bilateral subthalamic nuclei deep brain stimulation for intractable motor fluctuations and disabling dyskinesia. After this treatment course she experienced deterioration of motor symptoms and death eight years after disease onset. Post-mortem neuropathological examination revealed striatonigral degeneration and α-synuclein-positive glial cytoplasmic inclusions in brain stem nuclei, basal ganglia and white matter tracts, consistent with a neuropathological diagnosis of multiple system atrophy.</p> <p>Conclusions</p> <p>Multiple system atrophy can affect women of child-bearing age and pregnancy may be associated with marked disease progression.</p

The excess mortality risk of diabetes associated with functional decline in older adults: Results from a 7-year follow-up of a nationwide cohort in Taiwan

<p>Abstract</p> <p>Background</p> <p>Diabetes is associated with an increased risk of functional decline in older adults. Few studies have investigated the contribution of functional decline to excess mortality risk in older people with diabetes. The aim of this study was to examine how diabetes in combination with different levels of functional decline affects 7-year mortality in older adults.</p> <p>Methods</p> <p>We analyzed data from a nationally representative sample of people aged 65 years and over, participating in the 2001 National Health Interview Survey in Taiwan. A total of 1873 participants were followed through 2002-2008, of whom 286 (15.3%) had a history of diabetes confirmed by a medical professional. Participants were divided into three functional status groups: (1) high functioning-no limitations involving activities of daily living (ADLs), instrumental activities of daily living (IADLs), or physical functioning; (2) low functioning-limitations in one or more ADLs; (3) middle functioning-all participants in between groups 1 and 2.</p> <p>Results</p> <p>The crude mortality rate was 52.7 per 1,000 person-years in those with diabetes and 34.1 per 1,000 person-years in those without diabetes. After adjustment for other factors, diabetes alone was not associated with an increased mortality risk in those with high functioning. However, diabetes alone had a hazard ratio (HR) for mortality of 1.90 (95%CI = [1.02-3.53]) in those with middle functioning and 3.67 (95%CI = [1.55-8.69]) in those with low functioning. The presence of diabetes and one or more other chronic conditions was associated with a HR for mortality of 2.46 (95%CI = [1.61-3.77]) in those with middle functioning and 4.03 (95%CI = [2.31-7.03]) in those with low functioning.</p> <p>Conclusions</p> <p>Our results indicate that diabetes is not associated with increased mortality in those with high functioning. There was a gradient effect of functional decline on mortality in individuals with diabetes. Additionally, among participants with other chronic conditions, functional decline was associated with a greater burden of mortality in older adults with diabetes. These findings highlight the critical importance of the prevention of cardiovascular disease morbidity and the maintenance of functional abilities in order to reduce mortality risk in older adults with diabetes.</p

Estimation of progression of multi-state chronic disease using the Markov model and prevalence pool concept

<p>Abstract</p> <p>Background</p> <p>We propose a simple new method for estimating progression of a chronic disease with multi-state properties by unifying the prevalence pool concept with the Markov process model.</p> <p>Methods</p> <p>Estimation of progression rates in the multi-state model is performed using the E-M algorithm. This approach is applied to data on Type 2 diabetes screening.</p> <p>Results</p> <p>Good convergence of estimations is demonstrated. In contrast to previous Markov models, the major advantage of our proposed method is that integrating the prevalence pool equation (that the numbers entering the prevalence pool is equal to the number leaving it) into the likelihood function not only simplifies the likelihood function but makes estimation of parameters stable.</p> <p>Conclusion</p> <p>This approach may be useful in quantifying the progression of a variety of chronic diseases.</p

Elevated Aspartate and Alanine Aminotransferase Levels and Natural Death among Patients with Methamphetamine Dependence

Background: Methamphetamine is one of the fastest growing illicit drugs worldwide, causing multiple organ damage and excessive natural deaths. The authors aimed to identify potential laboratory indices and clinical characteristics associated with natural death through a two-phase study. Methods: Methamphetamine-dependent patients (n = 1,254) admitted to a psychiatric center in Taiwan between 1990 and 2007 were linked with a national mortality database for causes of death. Forty-eight subjects died of natural causes, and were defined as the case subjects. A time-efficient sex-and age-matched nested case-control study derived from the cohort was conducted first to explore the potential factors associated with natural death through a time-consuming standardized review of medical records. Then the identified potential factors were evaluated in the whole cohort to validate the findings. Results: In phase I, several potential factors associated with natural death were identified, including aspartate aminotransferase (AST), alanine aminotransferase (ALT), comorbid alcohol use disorder, and the prescription of antipsychotic drugs. In phase II, these factors were confirmed in the whole cohort using survival analysis. For the characteristics at the latest hospital admission, Cox proportional hazards models showed that the adjusted hazard ratios for natural death were 6.75 (p&lt;0.001) in the group with markedly elevated AST (&gt;80 U/L) and 2.66 (p&lt;0.05) in the group with mildly elevated AST (40-80 U/L), with reference to the control group (&gt;40 U/L). As for ALT, the adjusted hazard ratios were 5.41 (p&lt;0.001), and 1.44 (p&gt;0.05). Comorbid alcohol use disorder was associated with an increased risk of natural death, whereas administration of antipsychotic drugs was not associated with lowered risk. Conclusions: This study highlights the necessity of intensive follow-up for those with elevated AST and ALT levels and comorbid alcohol use disorder for preventing excessive natural deaths

Risk factors associated with symptomatic cholelithiasis in Taiwan: a population-based study

<p>Abstract</p> <p>Background</p> <p>Cholelithiasis has become a major health problem in Taiwan. The predominant type of gallstone found in Asian populations differs from that in the West, indicating possible differences in the etiology and risk factors for cholelithiasis. The aim of this study is to investigate the risk factors for cholelithiasis using data representative of the general population.</p> <p>Methods</p> <p>We performed a population-based, case-control study in which we analyzed medical data for 3725 patients newly diagnosed with cholelithiasis and 11175 gender- and age-matched controls with no history of cholelithiasis, using information obtained from the 2005 Registry for Beneficiaries of the National Health Insurance Research Database. Coexisting medical conditions were included in the analysis. Relative risks were estimated by adjusted odds ratio (OR) and 95% confidence interval (CI) using a multivariate logistic regression analysis.</p> <p>Results</p> <p>After controlling for the other covariates, multivariate logistic regression analysis identified the following as risk factors for cholelithiasis (in descending order of contribution): Among all patients - hepatitis C (OR = 2.78), cirrhosis (OR = 2.47), hepatitis B (OR = 2.00), obesity (OR = 1.89), and hyperlipidemia (OR = 1.54); Among women - hepatitis C (OR = 3.05), cirrhosis (OR = 1.92), obesity (OR = 1.91), menopause (OR = 1.61), hepatitis B (OR = 1.54), and hyperlipidemia (OR = 1.49). Diabetes mellitus appeared to have a marked influence on the development of cholelithiasis but was not identified as a significant independent risk factor for cholelithiasis.</p> <p>Conclusions</p> <p>The risk factors for cholelithiasis were obesity, hyperlipidemia, hepatitis B infection, hepatitis C infection, and cirrhosis in both genders, and menopause in females. Despite differences in the predominate type of gallstone in Asian versus Western populations, we identified no unique risk factors among the population of Taiwan.</p

Dimerization of Hepatitis E Virus Capsid Protein E2s Domain Is Essential for Virus–Host Interaction

Hepatitis E virus (HEV), a non-enveloped, positive-stranded RNA virus, is transmitted in a faecal-oral manner, and causes acute liver diseases in humans. The HEV capsid is made up of capsomeres consisting of homodimers of a single structural capsid protein forming the virus shell. These dimers are believed to protrude from the viral surface and to interact with host cells to initiate infection. To date, no structural information is available for any of the HEV proteins. Here, we report for the first time the crystal structure of the HEV capsid protein domain E2s, a protruding domain, together with functional studies to illustrate that this domain forms a tight homodimer and that this dimerization is essential for HEV–host interactions. In addition, we also show that the neutralizing antibody recognition site of HEV is located on the E2s domain. Our study will aid in the development of vaccines and, subsequently, specific inhibitors for HEV

Tidal and groundwater fluxes to a shallow, microtidal estuary : constraining inputs through field observations and hydrodynamic modeling

This paper is not subject to U.S. copyright. The definitive version was published in Estuaries and Coasts 35 (2012): 1285-1298, doi:10.1007/s12237-012-9515-x.Increased nutrient loading to estuaries has led to eutrophication, degraded water quality, and ecological transformations. Quantifying nutrient loads in systems with significant groundwater input can be difficult due to the challenge of measuring groundwater fluxes. We quantified tidal and freshwater fluxes over an 8-week period at the entrance of West Falmouth Harbor, Massachusetts, a eutrophic, groundwater-fed estuary. Fluxes were estimated from velocity and salinity measurements and a total exchange flow (TEF) methodology. Intermittent cross-sectional measurements of velocity and salinity were used to convert point measurements to cross-sectionally averaged values over the entire deployment (index relationships). The estimated mean freshwater flux (0.19 m3/s) for the 8-week period was mainly due to groundwater input (0.21 m3/s) with contributions from precipitation to the estuary surface (0.026 m3/s) and removal by evaporation (0.048 m3/s). Spring–neap variations in freshwater export that appeared in shorter-term averages were mostly artifacts of the index relationships. Hydrodynamic modeling with steady groundwater input demonstrated that while the TEF methodology resolves the freshwater flux signal, calibration of the index– salinity relationships during spring tide conditions only was responsible for most of the spring–neap signal. The mean freshwater flux over the entire period estimated from the combination of the index-velocity, index–salinity, and TEF calculations were consistent with the model, suggesting that this methodology is a reliable way of estimating freshwater fluxes in the estuary over timescales greater than the spring– neap cycle. Combining this type of field campaign with hydrodynamic modeling provides guidance for estimating both magnitude of groundwater input and estuarine storage of freshwater and sets the stage for robust estimation of the nutrient load in groundwater.Funding was provided by the USGS Coastal and Marine Geology Program and by National Science Foundation Award #0420575 from the Biocomplexity/Coupled Biogeochemical Cycles Program