Medical records were centralised Patients were

Medical records were centralised. Patients were MI-503 molecular weight compared with 60 controls with sarcoidosis.\n\nClinical examination showed more frequent crackles in patients than controls (45% versus 1.7%, respectively; p<0.001). On thoracic computed tomography scans, nodules (often multiple and with smooth margins), air bronchograms and halo signs were more frequent in patients than controls (80% versus 42%, respectively; p=0.004) as well as bronchiectasis (65% versus

23%, respectively; p<0.001). The micronodule distribution was perilymphatic in 100% of controls and in 42% of patients (p<0.001). Bronchoalveolar lavage analysis showed lower T-cell CD4/CD8 ratios in patients than in controls (mean +/- SD 1.6 +/- 1.1 versus 5.3 +/- 4, respectively; p<0.01). On pathological analysis, nodules and consolidations corresponded to granulomatous lesions with or without lymphocytic disorders in most cases. Mortality was higher in patients than controls (30% versus 0%, respectively) and resulted from common variable immunodeficiency complications.\n\nILD in CVID/GD presents a specific clinical picture and evolution that are markedly different from those of sarcoidosis.”
“Background: The loss of neurological function is closely related to axonal damage. Neurofilament subunits are concentrated in neurons and axons and have emerged as promising

biomarkers for neurodegeneration. Electrochemiluminescence (ECL) based assays are known to be of superior sensitivity Selleck S3I-201 and require less sample volume than conventional ELISAs.\n\nMethods: We developed an ECL based solid-phase sandwich immunoassay to measure the neurofilament heavy chain protein (NfH(SMI35)) in CSF. We employed commercially available buy A-1210477 antibodies as previously used in a conventional ELISA (Petzold et al., 2003; Petzold and Shaw, 2007). The optimised and validated assay was applied in a reference cohort and defined patient groups.\n\nResults: Analytical sensitivity (background plus three SD) of our assay was 2.4 pg/ml. The

mean intra-assay coefficient of variation (CV) was 4.8% and the inter-assay CV 8.4%. All measured control and patient samples produced signals well above background. Patients with multiple sclerosis (MS) (median 46.2 pg/ml, n = 95), amyotrophic lateral sclerosis (ALS) (160.1 pg/ml, n = 50), mild cognitive impairment/Alzheimer’s disease (MCI/AD) (65.6 pg/ml, n = 20), Guillain Barre syndrome (GBS) (91.0 pg/ml, n = 20) or subarachnoid hemorrhage (SAH) (345.0 pg/ml, n = 20) had higher CSF NfH(SM135) values than the reference cohort (27.1 pg/ml, n = 73, p <0.0001 for each comparison).\n\nConclusion: The new ECL based assay for NfH(SM135) in CSF is superior in terms of sensitivity, precision and accuracy to previously published methods (Petzold et al., 2003; Shaw et al., 2005; Teunissen et al., 2009).

Ratings for 0% polished

(brown rice) were substantially l

Ratings for 0% polished

(brown rice) were substantially lower than those of 2.3% polished rice, which were intermediate in ratings between 0% and 4.4% polishing. However, most of the consumers (93%) expressed a willingness to substitute brown or 2.3% polished rice, if affordable, after the taste tests and education on nutritional and health benefits of whole grains.\n\nConclusion: Though most consumers preferred polished white rice, education regarding health benefits may help this population switch to brown or undermilled rice. Cooking quality and appearance of the grains were perceived as the most important factors to consider when purchasing rice among Chennai urban adults.”
“Purpose: CD163 is a scavenger receptor which is exclusively expressed on monocytes/ macrophages and participates in modulation of inflammatory response. Crenolanib Protein Tyrosine Kinase inhibitor We aimed to evaluate ex vivo production of soluble CD163 (sCD163) by peripheral blood mononuclear cells (PBMC) from patients with systemic sclerosis (scleroderma, SSc).\n\nMaterial/ Methods: Concentration of sCD163 was measured by commercially available ELISA kit in the PBMC suparnates from 23 SSc patients and 16 age-and sex-matched healthy

controls (HC). Eighteen SSc patients were GSK2118436 mw subsequently followed for at least three years or until death whichever happened earlier. Disease progression was defined as death due to SSc-related selleck products organ complication, development of a new or progression of pre-existing SSc-related organ involvement.\n\nResults: PBMC from SSc patients released significantly greater amounts of sCD163 as compared with HC

(p<0.05). No significant associations between release of sCD163 by PBMC and baseline clinical or laboratory parameters of the disease could be found. However, concentration of sCD163 in cell culture supernates was significantly higher in 6 SSc patients who experienced subsequent progression of the disease as compared with 12 SSc patients with stable disease course over a 3-year follow-up period (p<0.05).\n\nConclusions: We show, for the first time, that PBMC from SSc release significantly greater amounts of sCD163 than do PBMC from healthy subjects. Evaluation of sCD163 production by PBMC ex vivo may serve as a new biomarker of disease progression. Further studies are required to evaluate the role of sCD163 in the development of SSc.”
“Following brain injury, return of consciousness and cough reflex are presumed to be associated with safe airway. We describe two patients who had a normal cough reflex, but impaired swallowing, which led to prolonged hospital stay. This report highlights the dissociation between the cough reflex and swallowing function in such patients.”
“Management of venous thromboembolism disease could be improved by new drugs with lower risk of bleeding and without the need of regular monitoring of anticoagulant effect.

An in

silico physiologically based pharmacokinetic (P

\n\nAn in

silico physiologically based pharmacokinetic (PBPK) model for poorly water-soluble, weakly HSP990 Cytoskeletal Signaling inhibitor basic drugs was used to generate plasma profiles of nelfinavir by coupling dissolution results and estimates of precipitation with standard gastrointestinal (Cl) parameters and the disposition pharmacokinetics of nelfinavir. In vitro dissolution of nelfinavir mesylate film-coated tablets was measured in biorelevant and compendial media. Drug precipitation in the small intestine was estimated from crystal growth theory. GI parameters (gastric emptying rate and fluid volume) appropriate to the dosing conditions (fasting and fed states) were used in the PBPK model. The disposition parameters of nelfinavir were estimated by fitting compartmental models to the in vivo oral PK data. The in vivo performance in each prandial state was simulated with the PBPK model, and predicted values for AUC and C(max) were compared to observed values.\n\nDissolution results in FaSSIF-V2 and FeSSIF-V2, simulating the fasting and fed small intestinal conditions, respectively, correctly predicted that there would be a positive food effect for nelfinavir AZD4547 molecular weight mesylate, but overestimated the food effect observed in healthy human volunteers. In order to better predict the food effect, an in silico PBPK simulation model using STELLA software was evolved.

Results with the model indicated that invoking drug precipitation in the small intestine is necessary to describe the in vivo performance of nelfinavir mesylate in the fasted state, whereas a good prediction under fed state conditions is obtained without assuming any precipitation. In vitro-in silico-in vivo relationships (IVISIV-R) may thus be a helpful tool in understanding the critical parameters that affect the oral absorption of poorly soluble weak bases. (C) 2011 Elsevier B.V. All rights reserved.”
“Sterile alpha motif domain-containing 11

(SAMD11) is evolutionarily conserved from zebrafish to human. Mouse Samd11 is predominantly expressed in developing retinal photoreceptors and the adult pineal gland, and its transcription is directly regulated by Z-DEVD-FMK the cone-rod homeodomain protein Crx. However, there has been little research on human SAMD11. To investigate the function of human SAMD11, we first cloned its coding sequence (CDS) and identified up to 45 novel alternative splice variants (ASVs). Mouse Samd11 ASVs were also identified by aligning the mouse Samd11 expressed sequence tags (ESTs) with the annotated sequence. However, the range of expression and transcriptional regulation of SAMD11 differs between human and mouse. Human SAMD11 was found to be widely expressed in many cell lines and ocular tissues and its transcription was not regulated by CRX, OTX2 or NR2E3 proteins.

The antimetastatic activity of iRGD may provide a significant add

The antimetastatic activity of iRGD may provide a significant additional benefit when this peptide is used for drug delivery to tumors. (C) 2014 AACR.”
“Background: The validity of ensemble averaging on event-related potential (ERP) data has been questioned, due to its assumption that the AG-881 cell line ERP is identical across trials. Thus, there is a need for preliminary testing for cluster structure in the data. New method: We propose a complete pipeline for the cluster analysis of ERP data. To increase the signal-to-noise (SNR) ratio of the raw single-trials, we used a denoising method based on Empirical Mode Decomposition (EMD). Next, we used a bootstrap-based method

to determine the number of clusters, through a measure called the Stability Index (SI). We then used a clustering algorithm based on a Genetic Algorithm (GA) to define initial cluster centroids for subsequent k-means clustering. Finally, we visualised the clustering results through a scheme based on Principal Component Analysis (PCA). Results: After validating the pipeline on simulated data, we tested it on data from two experiments a P300 speller paradigm on a single subject and a language processing study on 25 subjects. CA4P inhibitor Results revealed evidence for the existence of 6 clusters in one experimental condition from the language

processing study. Further, a two-way chi-square test revealed an influence of subject on cluster membership. Comparison with existing method(s): Our analysis operates on denoised single-trials, the number of clusters are determined selleck chemicals llc in a principled manner and the results are presented through an intuitive visualisation. Conclusions: Given the cluster structure in some experimental conditions, we suggest application of cluster analysis as a preliminary step before ensemble averaging. (C) 2015 Elsevier B.V. All rights reserved.”
“Taste, smell, and chemical irritation (so-called

trigeminal sensation) combine in our daily experience to produce the supramodal sensation of flavor, are processed by partly overlapping neural mechanisms, and show functional interconnectivity in experiments. Given their collaboration in flavor formation and the well-established connections between these senses, it is plausible that polymodal detection mechanisms might contribute to individual differences in measured sensitivity. One would expect the existence of a general chemosensory sensitivity factor to result in associations among taste, smell, and trigeminal stimulation thresholds. Measures of 5 detection thresholds from all the chemical senses were assessed in the same group of young healthy subjects (n = 57). An unbiased principal components analysis (PCA) yielded a 2-component solution. Component 1, on which taste thresholds loaded strongly, accounted for 29.4% of the total variance.

This effect was equivalent in size to the effect observed for con

This effect was equivalent in size to the effect observed for controls, demonstrating normal face-sensitivity of the N170 component in DP. Face inversion enhanced N170 amplitudes in the

control group, but not for DPs, suggesting that many DPs do not differentiate between upright and inverted faces in the typical manner. These N170 face inversion effects were present for younger but not older controls, while they were absent for both younger and older DPs. Results suggest that the early face-sensitivity of visual processing is preserved in most individuals with DP, but that the face processing system in many DPs is not selectively tuned to the canonical upright orientation of faces. (C) 2012 Elsevier Ltd. All rights reserved.”
“Background. Castleman disease (CD), or angiofollicular www.selleckchem.com/products/cftrinh-172.html lymph-node hyperplasia, is an atypical lymphoproliferative disorder with heterogeneous clinical manifestations. Renal involvement in CD has been described in only single-case reports, which have included various types of renal diseases.\n\nMethods. Nineteen selleck chemical patients with histologically documented CD and renal biopsies available were included. Clinical features and renal histological findings were reviewed, and the available

samples were immunolabelled with anti-vascular endothelial growth factor (VEGF) antibody.\n\nResults. Nineteen CD cases were identified: 89% were multicentric, and 84% were of the plasma-cell or mixed type. Four cases (21%) were associated with human immunodeficiency virus (HIV) infection. Among

HIV-negative patients, two main patterns of renal involvement were found: (i) a small-vessel lesions group (SVL) (60%) with endotheliosis Quizartinib cost and glomerular double contours in all patients and with superimposed glomerular/arteriolar thrombi or mesangiolysis in most; and (ii) AA amyloidosis (20%). Renal histology was more heterogeneous among HIV-positive patients. Decreases in glomerular VEGF were observed only in some patients with SVL, whereas VEGF staining was normal in all other histological groups. Interestingly, glomerular VEGF loss associated with SVL was correlated with plasma C-reactive protein levels, a marker of CD activity.\n\nConclusions. Small-vessel lesions are the most frequent renal involvement in CD, whereas loss of glomerular VEGF is correlated with CD activity and could have a role in SVL pathophysiology.”
“Compared with unmodified F127, the concentration range exhibiting sol-gel transition increased for the CL4-F127-CL4 (F-CL4); however, it decreased for the CL12-F127-CL12 (F-CL12), even though both F-CL4 and F-CL12 were hydrophobically modified by the oligocaprolactone (OCL). To understand the abnormal behavior of the OCL end capped F127, the difference in basic nanoassemblies among the F127, F-CL4, and F-CL12 were investigated at a low concentration of 0.10 wt % as well as at high concentrations exhibiting sol-gel transitions.

Cytotoxic effect of lappaconitine and oxaliplatin on A549 lung ca

Cytotoxic effect of lappaconitine and oxaliplatin on A549 lung cancer cells were examined by MTT assay. Lappaconitine-and

oxaliplatin-induced apoptosis were detected by flow cytometry. Expression of CyclinE1 and selleck compound VEGF mRNA were measured by RT-PCR. Ultrastructure change of lung cancer cells was observed by atomic force microscopy. LA could inhibit the proliferation of A549 cells with a dose-dependent character. The inhibitory rate of A549 induced by LA combined with OXAL was significantly increased. LA might increase the cytotoxic and apoptotic effect of OXAL in A549 cells. Combined with LA, apoptotic change of OXAL on lung cancer cells was increased. Furthermore, LA alone or together with OXAL can induce G1/G0 arrest through inhibiting CyclinE1 mRNA expression. LA alone or together with OXAL might downregulate VEGF-A mRNA expression. Compared with oxalipaltin alone, the combination Z VAD FMK of lappaconitine and oxaliplatin against A549 lung cancer cells might be related to synergistic apoptotic effect, and was perhaps associated with downregulation of CyclinE1 and VEGF-A expression.”
“Study Design. Retrospective radiographic analysis.

Objective. To retrospectively review a group of patients undergoing anterior

cervical discectomy and fusion (ACDF) to determine the relative risk of adjacent level disc degeneration after incorrect needle localization.

Summary of Background Data. The needle puncture technique is a well-established method to cause disc degeneration in experimental animal studies. The risk for accelerated degeneration because of needle puncture in humans is unknown.

Methods. A retrospective radiographic analysis of 87 consecutive patients

after single or 2-level ACDF with anterior plate instrumentation was performed. Perioperative and follow-up radiographs were used to grade disc degeneration according to a previously described https://www.selleckchem.com/products/OSI-906.html scale.

Results. Eighty-seven patients were included in the study (36 underwent 1-level ACDF, and 51 underwent 2-level ACDF). Seventy-two had correct needle localization at the level of planned surgery; 15 had incorrect needle localization (1 level above the operative level). There were no differences between the 2 groups in age, sex and length of follow-up. Patients in the incorrectly marked group were statistically more likely to demonstrate progressive disc degeneration with an odds ratio of 3.2. There was no correlation between age and length of follow-up with development of disc degeneration.

Conclusion. There is a 3-fold increase in risk of developing adjacent level disc degeneration in incorrectly marked discs after ACDF at short-term follow-up. This may indicate that either needle related trauma or unnecessary surgical dissection contributes to accelerated adjacent segment degeneration.

CONCLUSION: Rapid CRP testing helped exclude PTB, and may be a va

CONCLUSION: Rapid CRP testing helped exclude PTB, and may be a valuable test in assisting nurses and physicians in TB-endemic

regions.”
“Background: Cytogenetic evaluation is a key component of the diagnosis and prognosis of chronic lymphocytic leukemia (CLL). We performed oligonucleotide-based comparative genomic hybridization microarray analysis on 34 samples with CLL and known abnormal karyotypes previously determined by cytogenetics and/or fluorescence in situ hybridization (FISH).

Results: Using a custom GKT137831 inhibitor designed microarray that targets > 1800 genes involved in hematologic disease and other malignancies, we identified additional cryptic aberrations and novel findings in 59% of cases. These included gains and losses of genes associated with cell

cycle regulation, apoptosis and susceptibility loci on 3p21.31, 5q35.2q35.3, 10q23.31q23.33, 11q22.3, and 22q11.23.

Conclusions: PCI-34051 supplier Our results show that microarray analysis will detect known aberrations, including microscopic and cryptic alterations. In addition, novel genomic changes will be uncovered that may become important prognostic predictors or treatment targets for CLL in the future.”
“The fig tree (Ficus carica L.) is of significant socioeconomic importance in Turkey, with 25% of the world’s fig production. Genetic variation and relationships among 14 wild-grown figs sampled from Coruh Valley in Turkey were characterized by random amplified polymorphic DNA (RAPD). Ninety-eight DNA fragments were scored

after amplification of DNA samples with 13 random primers; 70% of the scored bands were polymorphic. Genetic distances between the fig genotypes LY2835219 in vitro ranged from 0.21 to 0.62. Genotypes 08-ART-02 and 08-ART-06 were found to be the most closely related, whereas 08-ART-09 and 08-ART-10 were the most distant. The 14 wild-grown genotypes were grouped into six main clusters and one outgroup. We conclude that RAPD analysis is efficient for genotyping wild-grown fig genotypes.”
“OBJECTIVE: To update the evidence-based recommendations for the prevention and management of hypertension in adults for 2009.

OPTIONS AND OUTCOMES: For lifestyle and pharmacological interventions, evidence front randomized controlled trials and systematic reviews of trials was preferentially reviewed. Changes in cardiovascular morbidity and mortality were the primary outcomes of interest. However, for lifestyle interventions, blood pressure lowering was accepted as a primary outcome given the lack of long-term morbidity and mortality data in this field. Progression of kidney dysfunction was also accepted as a clinically relevant primary outcome among patients with chronic kidney disease.

EVIDENCE: A Cochrane collaboration librarian conductcd an independent MEDLINE search front 2007 to August 2008 to Update the 2008 recommendations.

The patient was admitted with fever and circumferential swelling

The patient was admitted with fever and circumferential swelling in the paradorsal region, which was evident only in the flexed back position. A chest X-ray showed a pleural effusion with pneumonitis and dorsal kyphosis. Following the yield of Staphylococcus aureus from blood cultures, the initial therapy of ceftriaxone and amikacin was changed to vancomycin. However, the dorsal swelling increased further and imaging investigations showed destruction of the vertebral bodies D8-D10 and

surrounding tissue swelling. Vancomycin was changed to linezolid, and the patient began to improve; selleck inhibitor a full recovery was made. Our case suggests that even if spondylodiscitis is rare in the pediatric age-group, particularly as a complication of staphylococcal sepsis, early diagnosis and prompt and appropriate therapy are important to prevent severe complications.

(C) 2009 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.”
“Vitamin Selleck TPX-0005 D deficiency has been correlated with increased rates of infection. Since the early 19th century, both environmental (i.e,, sunlight) and dietary sources (cod liver) of vitamin D have been identified as treatments for TB. The recent discovery that vitamin D induces antimicrobial peptide gene expression explains, in part, the ‘antibiotic’ effect of vitamin D and has greatly renewed interest in the ability of vitamin D to improve immune function, Subsequent work indicates that this regulation is biologically

important for the response of the innate immune system to wounds and infection and that deficiency may lead to suboptimal responses toward bacterial and viral infections. The regulation of the cathelicidin antimicrobial peptide gene is a human/primate-specific adaptation and is not conserved in other mammals. The capacity of the vitamin D receptor to act as a high-affinity receptor for vitamin D and a low-affinity selleck screening library receptor for secondary bile acids and potentially other novel nutritional compounds suggests that the evolutionary selection to place the cathelicidin gene under control of the vitamin D receptor allows for its regulation under both endocrine and xenobiotic response systems. Future studies in both humans and humanized mouse models will elucidate the importance of this regulation and lead to the development of potential therapeutic applications.

The absence of RAS and ERK1 and positivity for BRAF and ERK2 were

The absence of RAS and ERK1 and positivity for BRAF and ERK2 were associated with higher histological grade, vascular

invasion, and metastasis. Expression of MEK2 was significantly linked to vascular invasion (P = 0.043). The CDKN2A and MAPK pathways require further study in mucosal melanomas, but our results highlight the significance of important alterations, particularly with regard to histological indicators of poor prognosis in primary oral mucosal melanomas, independent of UV exposure.”
“Dalfampridine extended release (ER) 10 mg is an oral tablet form of the potassium (K+) channel-blocking compounded dalfampridine, also known as fampridine, and chemically 4-aminopyridine or 4-AP, which received regulatory approval in the United States for the treatment of walking in patients with multiple sclerosis (MS) in January 2010. Two pivotal Phase 3 clinical trials demonstrated PRIMA-1MET order significant improvements in walking in patients with the four Selisistat ic50 primary forms of MS

following administration of dalfampridine ER tablets 10 mg twice daily. The drug is thought to act by restoring conduction in focally demyelinated axons and by enhancing neurotransmission, thereby leading to improved neurological function. This review describes how dalfampridine represents a new pharmacotherapeutic approach to the clinical management of mobility impairment. It describes the mechanism of action and chemistry of dalfampridine ER, its pharmacokinetics, tolerability, and side effects, and the outcomes of multicenter trials showing its efficacy in improving walking speed. Clinician and patient global assessments, as well as patient self-assessment of the impact of MS on their gait disability, confirm clinically

relevant benefit from the therapy. Prexasertib Patients tolerate the drug well and their improvement in terms of household and community ambulation, inferred from analysis of pooled data from several studies, is likely to translate into benefits in the performance of instrumental activities of daily living and a reduction in the neuropsychiatric burden of disease.”
“The topic of distinguishing atypical fibroxanthoma (AFX) from undifferentiated pleomorphic sarcoma (UPS), formerly malignant fibrous histiocytoma, is highly controversial. Although their clinical behavior is disparate, AFX and UPS commonly appear nearly identical on routine histopathologic examination. Although conceptually useful, subcategorization of UPS into superficial (confined to the dermis and subcutaneous tissue) and deep (involvement of fascia and deeper structures) types has not improved our ability to differentiate UPS from AFX. Numerous authors have purported LN-2 (CD74) immunopositivity as able to distinguish UPS from AFX and to predict those rare AFX likely to behave aggressively, although only a single prior study has been dedicated to evaluating this marker.

Surface functionalization was studied by X-ray photoelectron spec

Surface functionalization was studied by X-ray photoelectron spectroscopy (XPS). Thermal properties were analyzed by differential scanning calorimetry (DSC). The hydrophilicity increment was confirmed by pure water contact angle and swelling measurements. The filtration capability of the modified membrane was analyzed by determining color, turbidity, and chemical oxygen demand (COD) removal from a residual raw water.

The results indicated that the contact selleck compound angle of pure water on the grafted membrane decreased from 90 degrees to 57 degrees. The modified membrane shows filtration capability by removing color in 52% and reducing 95% of turbidity. (C) 2011 Wiley Periodicals, Inc. J Appl Polym Sci,

2012″
“Background: Polyunsaturated fatty acids and fish may influence bone health.

Objective: We aimed to examine associations between dietary polyunsaturated fatty acid and fish intakes and hip bone mineral density (BMD) at baseline (1988-1989; n = 854) and changes 4 y later in adults (n = 623) with a mean age of 75 y in the Framingham Osteoporosis Study.

Design: BMD measures were regressed on energy-adjusted quartiles of fatty acid intakes [n-3 (omega-3): alpha-linolenic acid, eicosapentaenoic acid (EPA), docosahexaenoic SRT2104 price acid (DHA), and EPA+ DHA; n-6 (omega-6): linoleic acid (LA) and arachidonic acid (AA); and n-6: n-3 ratio] and on categorized fish intakes, with adjustment for covariates. Effect modification by EPA+DHA intake was tested for n-6 exposures.

Results: High intakes (>= 3 servings/wk) of fish relative to lower intakes were associated with maintenance of femoral neck BMD (FN-BMD) in men (dark fish + tuna, dark fish, and tuna) and in women (dark fish) (P < 0.05). Significant interactions between AA and EPA+DHA intakes were observed cross-sectionally in women and longitudinally in men. In women with EPA+DHA intakes at or above the median, those with the PXD101 highest AA intakes had a higher

mean baseline FN-BMD than did those with the lowest intakes (quartile 4 compared with quartile 1: P = 0.03, P for trend = 0.02). In men with the lowest EPA+DHA intakes (quartile 1), those with the highest intakes of AA (quartile 4) lost more FN-BMD than did men with the lowest intakes of AA (quartile 1; P = 0.04). LA intake tended to be associated with FN-BMD loss in women (P for trend < 0.06).

Conclusions: Fish consumption may protect against bone loss. The protective effects of a high AA intake may be dependent on the amount of EPA+DHA intake. Am J Clin Nutr 2011;93:1142-51.”
“Background: Prior studies on the course of alcohol use disorders have reported a “”telescoping”" effect with women progressing from drinking initiation to alcohol dependence faster than men.