8 days) than in the previous study These two factors, as well as

8 days) than in the previous study. These two factors, as well as the fact that our research was conducted during the summer peak, may led to the higher incidence rate of diarrhea, as found in several studies.15–17 Although up to 90% of our backpackers perceived the risk of travelers’ diarrhea while traveling in Southeast Asia, their actual practices were far from ideal. Up to 95.7% of participants had bought food from street vendors, 92.5% had drunk beverages with ice-cubes, 34.6% had eaten leftover food from a previous meal, and 27.5% had drunk tap water. These low compliance rates with safe behaviors have been found in many studies.10,18 We were unable to

selleck kinase inhibitor demonstrate any relationship between each practice and diarrheal attack, except for drinking beverages with ice/ice-cubes, which was more common in the diarrheal group than the nondiarrheal group. As in all cross-sectional studies, Inhibitor Library screening we could not assess the causal relationship between these two parameters. Unfortunately, even longitudinal studies have failed to show that adherence to sensible practices will reduce the risk of diarrhea.18–21 More than half of our participants carried some

kind of antidiarrheal medication. Most (71%) carried antimotility medications; although their efficacy, that is, their ability to reduce the number of stools passed, has been proven,22 they should be used with care, especially when used alone for diarrhea associated with high fever, chills, or bloody mucus diarrhea.4 Antimotility medications may actually worsen the clinical course of invasive diarrhea,23 so that antibiotic treatment should be considered. Unfortunately, we did not assess backpackers’ knowledge of when and how to use antimotility medications appropriately. Most episodes of travelers’ diarrhea

in our series were mild; about 80% of diarrheal episodes caused <6 bowel movements per day, and lasted <4 days. Most cases recovered spontaneously, with only 3.2% Non-specific serine/threonine protein kinase needing hospitalization. These general characteristics of travelers’ diarrhea in our study were well-matched with most previous studies.4,9,24 Although it may seem a mild disease, its nonmedical impacts should not be neglected. Diarrheal episodes can force a significant number of travelers (11.3% in our study, to 40% in some reports4,17) to delay or cancel their trip, incurring additional expense. The lower levels of impact reported in our study may be due to the particular characteristics of backpackers, that is, that they usually have more flexible itineraries than general or business travelers. This study had several limitations. First, our data collection was done exclusively in Khao San Road area. Although it is a well-known, main backpacker hub in Southeast Asia, data from single site could not be a perfect representative of the whole backpacker group in the region. Apart from that, our data collection was done only in summer time and seasonality may have affected the incidence of travelers’ diarrhea.

1 Phages ST7, ST70, ST79 and ST88 have isometric heads (54 nm in

1. Phages ST7, ST70, ST79 and ST88 have isometric heads (54 nm in diameter) and long contractile tails (148 nm in length and 17 nm in width) with long tail sheets and tail fibers while phages ST2 and ST96 have an average head diameter of 60 nm

with shorter tail sheets without tail fibers (tail length of 27 and 60 nm). From the morphology and nucleic acid types of genetic material, typing was based on guidelines of the International Committee on Taxonomy of Viruses (ICTV) (Ackermann, 2003), all phages belong to Myoviridae family and Bradley’s group A1 (Ackermann, 2001). In this study, all phage nucleic acids were dsDNA. CX-5461 molecular weight PstI and XhoI restriction enzymes provided distinguishable patterns after separation by agarose gel electrophoresis (Fig. 2). The estimated genome size of ST2, ST7, ST70, ST79, ST88 and ST96 phages were 40.9, 32.5, 24.0, 31.7, 32.3 and 54.6 kb. The ST7 and ST88 yielded very similar digestion patterns with two

enzymes, had similar genome sizes and their morphology under an electron microscope looked similar. Nevertheless, further investigations PD0325901 purchase should be made before it can be concluded as to whether they are the same phage. The ST2, ST7, ST70, ST79, ST88 and ST96 phages were able to lyse 78%, 41%, 65%, 71%, 41% and 67% of tested B. pseudomallei isolates. Only ST2 and ST96 phages could lyse B. thailandensis and all phages formed tiny clear plaques on B. mallei lawn. None of the phages could form any plaques on a wide range of other Gram-negative or Gram-positive bacteria tested in this

experiment (Table 1). The highest phage titer PIK-5 was obtained by infection of B. pseudomallei P37 (1 × 109 CFU mL−1) with ST79 and ST96 at an optimal MOI of 0.1. They were able to dramatically reduce OD550 nm of B. pseudomallei P37 in liquid culture from 0.3 OD550 nm to a complete lysis (OD almost zero) within 5 h after phage addition. The number of bacteria tended to increase again after 12 h (Fig. 3). The experiment was performed in triplicate. Phage ST79 was selected for further growth parameter characterization as this novel lytic phage had a broader host range of tested B. pseudomallei isolates. The eclipse and latent periods were 20 and 30 min. The average burst size, calculated by the ratio of the final count of liberated phage particles to the initial count of infected bacterial cells during the latent period, was 304 PFU per infected cell at 37 °C (Fig. 4). The experiment was performed in triplicate. Since 1959, over 5100 phages have been examined by electron microscopy, of which 96% are tailed phages belonging to Siphoviridae (61%), Myoviridae (25%) and Podoviridae (14%) (Ackermann, 2003). Phages are abundant in the environment and play an important role in the ecosystem. Several lytic phages have been isolated and characterized for therapeutic usage in animals and humans such as GJ1-GJ6, which are active against O149 enterotoxigenic E. coli, e11/2, e4/1c and pp01 against E. coli O157:H7, FGCSSa1 against Salmonella spp.

This is in part because medical training does not seem to include

This is in part because medical training does not seem to include relevant exposure to the pharmacists’; role and function, and also prescribing responsibilities ERK inhibitor datasheet are part of a packed curriculum. The impact of the Trust’s existing induction programme on prescribing practices and understanding the pharmacist role was considered of

limited use. Although the national competency exam may be reassuring evidence of prescribing competency, it is unlikely it will improve this relationship. We acknowledge the limitations of conducting this study in a single hospital with a relatively small sample size. 1. Dornan T, Ashcroft D, Heathfield H, et al. An in-depth investigation into the causes of prescribing errors by foundation trainees in relation to their medical education: EQUIP study. 2009. Final report to the General Medical Council, University of Manchester: School of Pharmacy and Pharmaceutical medicine and School of Medicine. 2. Ross S et al. Perceived causes of prescribing errors by junior doctors in hospital inpatients: a study from the PROTECT programme. BMJ Qual Saf 2013; 22: 97–102. M. Patel, O. Eradiri Colchester Hospital University NHS Foundation Trust, Colchester, Essex, UK SAM potentially prevents harm from delays

and omissions of medicines. SAM significantly reduced omitted doses (9%, v 13% in the non-SAM group). SAM, by this evidence, is a justified safety tool against omissions. The National Patient Safety Agency has identified LGK-974 order omitted and delayed doses as the second highest cause of medication incidents, resulting in significant harm to hospital patients.1 Our Trust adopted assorted measures to address this, culminating in annual trust-wide omission rates of only 14% and 13% in 2011 and 2012, respectively. SAM is a national medicines management strategy2, encouraging patients, if competent, to administer their own medicines, brought into hospital

or from SAM (pre-labelled) Methane monooxygenase packs. SAM is an established practice at our 600-bed Trust. Aim: To assess the contribution of SAM to reducing omitted doses. A prospective audit was conducted by clinical pharmacists and technicians (using a previously piloted tool that identified SAM patients, the medicines omitted and the reasons for omission) on non-SAM patients on their respective wards, over two days. Following the return of completed audit tools, the authors personally collected data, at random, for the corresponding number of SAM patients on each ward. Data were recorded on a Microsoft Excel spreadsheet for statistical analysis. Ethics approval was not required. Audit standards were derived from our Trust SAM policy, and set to 100% for the following: a) SAM patients should be asked if they have taken their medicines; b) omitted doses should have reasons documented. Data were collected from 14 wards that had SAM patients, of the 21 wards at our Trust. The total sample size was 86 patients (43 each of SAM and non-SAM).

Using chart review, we have determined that 75% of those entering

Using chart review, we have determined that 75% of those entering care in the VA for HIV infection initiate their first course of cART after coming to the VA. To ensure adequate this website follow-up time, we identified subjects who initiated their first course of cART in the VA between 1 January 1997 and 1 August 2002. We used pharmacy data to identify individuals initiating a minimum of three antiretroviral medications and laboratory data to determine that

they had received a minimal evaluation (CD4 cell count, HIV-RNA and haemoglobin) within 6 months of initiating cART. Available data included demographic factors (age, race/ethnicity and gender), administrative diagnostic codes [International Statistical Classification of Diseases and Related Health Problems (ICD)-9 codes], routinely collected clinical laboratory data, pharmacy data and long-term mortality. All laboratory data were collected from the clinical sites through the Immunology Case Registry [26]. Pharmacy data are drawn from the national VA Pharmacy Benefits Management Package [27]. ICD-9 codes

were used to determine diagnoses of drug abuse or dependence, alcohol abuse or dependence, and AIDS-defining illnesses. Hepatitis C was defined as a positive antibody, qualitative or quantitative HIV RNA, or ICD-9 codes. Hepatitis B was defined as a positive PI3K targets surface antigen test or ICD-9 codes. In all cases in which ICD-9 codes were used, two out-patient or one in-patient code was required before the condition was considered present. This approach improves the accuracy of ICD-9 codes when compared with chart review [28]. The specific codes used can be found at our website (http://VAcohort.org). All cause mortality data using VA data sources have been demonstrated to be accurate and complete when compared with the National Death Registry [29,30]. We ran univariable descriptive statistics and estimated the association between biomarkers using Spearman rank for continuous variables

and χ2 for dichotomous markers. We then split the sample. Those Diflunisal who initiated treatment after 31 December 1998 were assigned to the development set and those who initiated treatment on or before this date were reserved for validation. We initially standardized the maximal observation interval for both samples to 6 years, but later conducted sensitivity analyses around this maximal survival window. We chose a nonrandom split based on calendar time to determine the temporal generalizability of our findings [32]. After each model had been fully specified we used the assigned risk estimates from the model to rank patients according to risk from highest to lowest risk of mortality. We compared Poisson, Weibull and Cox survival models and found that differences in distributional assumptions over the 6-year window did not substantially alter coefficient weights. We present Poisson analyses, as these results are the most directly interpretable.

A secretion assay showed the secretion of VopC in the wild type a

A secretion assay showed the secretion of VopC in the wild type and the ΔvocC strain

complemented with a vocC complementation plasmid (pvocC) (Fig. 2a). In contrast, VopC was not observed in the supernatant or the bacterial pellet of the vocC knockout strain (ΔvocC). VopL, which was also found to interact with VocC in the screening assay, was not visible in the supernatant of ∆vocC, as assayed by Western blotting using an anti-VopL antibody (Fig. 2a). Although faint bands were detected in all samples using an anti-VopL antibody, these bands were confirmed to be nonspecific using the ΔvopL mutant strain (data not shown). To evaluate the possibility that the absence of VopC in the supernatant of ∆vocC was caused by a small selleckchem amount of VopC expressed in the bacterial

pellets, we introduced MS-275 clinical trial a plasmid encoding vopC into the ∆vocC strain. As shown in Fig. 2a, although overexpressed VopC was detected in bacterial pellets, it was not detected in the supernatant. To examine whether VocC might be required by all T3SS systems for protein secretion, VopD1 (T3SS1 translocon) and VopD2 (T3SS2 translocon) were probed using antisera against VopD1 and VopD2, respectively. The secretion of VopD1 and VopD2 by T3SS1 or T3SS2 was observed in the vocC mutant, and a lower level of VopD1 was observed in the cell pellet of the vocC-complemented ∆vocC strain. The transcriptional regulation of T3SS2 and T3SS1 is influenced by each other, especially with the addition of bile (Gotoh et al., 2010); these results might explain our observation of a lower level of

VopD1 in the vocC-complemented ∆vocC strain. Some T3SS-associated chaperones can regulate the transcription of T3SS-associated genes (Darwin & Miller, 2001; Pilonieta & Munson, 2008). Therefore, it was possible that VocC regulated the transcription of VopC because lower levels of VopC protein were observed in the supernatant these and the bacterial pellet in the secretion assay. The transcriptional level of vopC in the ΔvocC strain was evaluated using semi-quantitative RT-PCR. The levels of both vopC and vopD2 were indistinguishable between wild-type and ΔvocC strains grown under T3SS-inducing conditions (Fig. 2b). Moreover, the translational level of vopC in the ∆vocC strain was evaluated using a translational fusion to amino acids 2–405 of CyaA from B. pertussis. The isogenic mutants of VopC1–30–CyaA in the wild-type and ∆vocC strains expressed a similar level of the translational fusion under the same conditions as the secretion assay (Fig. 2c). Similar transcriptional and translational levels of vopC in both wild-type and ∆vocC strains indicated that the decreased protein level of VopC in the absence of VocC might be caused by the degradation of VopC.

In 2011, MSM accounted for 54% of all new HIV diagnoses in Spain

In 2011, MSM accounted for 54% of all new HIV diagnoses in Spain [1]. HIV

testing is an important part of HIV prevention activities, as it is required to diagnose HIV infection. Based on the results of HIV testing, prevention programmes focused on the HIV status of the person may be very appropriate to reduce acquisition and transmission of the infection. The advantage of being tested regularly for HIV is that early diagnosis is vital for timely access to treatment and to control the spread of the virus. Some studies have reported that, once people know they are HIV-positive, many of them reduce high-risk sexual behaviours compared with untested people [2]. Diagnosis is also desirable because it allows GSK2118436 mw early initiation of antiretroviral therapy, which reduces viral load, which in turn may reduce the risk of transmission GSI-IX in vivo of HIV. Serostatus awareness is beneficial at the individual and population levels, and is in line with the

‘test and treat’ approach to control the spread of HIV [3]. Undiagnosed HIV infection is a major potential source of the spread of infection. An important number of new infections are acquired from sexual partners whose infection is undiagnosed [4, 5]. Therefore, to monitor the epidemic among MSM, it is important to know why, when and where they are tested or, conversely, why individuals do not seek HIV testing or refuse it if it is offered. In view of the relatively limited knowledge regarding MSM who have never been tested for HIV in Spain, the aims of this study were to describe the sociodemographic profile of MSM who have never been tested for

HIV, and to analyse factors associated with never having been tested for HIV. A total of 13 753 participants completed the survey. The inclusion criteria were: being male; living in Spain; being at Carnitine dehydrogenase or over the age of sexual consent in Spain; having sexual attraction to men and/or having had sex with men; indicating having understood the nature and purpose of the study; and providing consent to take part in the study. After exclusion of individuals who did not fulfill the inclusion criteria or with inconsistent data, the final sample consisted of 13 111 men. The questionnaire was available in 25 European languages simultaneously and included core questions on sociodemographic characteristics, risk behaviours, history of diagnoses of HIV infection and other STIs, HIV prevention needs (information, access to condoms, etc.), and service uptake. The European MSM Internet Survey (EMIS) was approved by the Research Ethics Committee of the University of Portsmouth, UK (REC application number 08/09:21). This study had a collective approach, including public health, academic and nongovernmental organization (NGO) sectors, and social media. The EMIS was available online for completion over the course of 12 weeks in 2010. Promotion occurred mainly through national and transnational commercial and NGO websites, and social networking websites.

4 It should be noted that anti-mitochondrial antibody-negative PB

4 It should be noted that anti-mitochondrial antibody-negative PBC and false-positive anti-transglutaminase antibodies have been reported in this context.19 and 20 As in the case of AIH, the impact of gluten avoidance is not well established, but it is determinant to improve symptomatic CD and to prevent complications.2 and 20 A relation between CD and PSC has been suggested in several case reports and in a population-based study. However the

strength of this association Enzalutamide is not clearly determined and the benefit of gluten exclusion from the diet was not yet demonstrated.2 and 13 Nonalcoholic fatty liver disease (NAFLD) and steatohepatitis (NASH) are common disorders in the general population and in celiac patients. Metformin in vivo Studies found a prevalence of CD in about 3% of individuals with

NAFL and NASH.21 Obesity, a major risk factor for nonalcoholic liver disease, is common in patients with CD not only after but also before gluten withdrawal, which could explain the association between these disorders.22 Additional etiopathogenic mechanisms may be the increased intestinal permeability, resulting in bacterial translocation and production of proinflammatory factors, and malabsorption leading to chronic deficiency of lipotropic molecules.23 and 24 The correlations among CD, obesity and liver disease must be taken into account when establishing the diagnosis and treating celiac patients presenting with elevated liver enzymes. Acute liver failure and advanced liver disease deserve a special consideration. There are several cases reported in literature and CD was found to be Rutecarpine up to 10 times more frequent among patients with chronic liver disease than in the general population.25 The study by Kaukinen and colleagues12 found a high prevalence of CD (4.3%) in patients who underwent liver transplantation. Autoimmune disorders, such as PBC, PSC and AIH were the main etiologies of end-stage liver disease leading to transplantation. This study also describes 4 cases of patients with advanced liver disease

who were found to have CD, all of them improving significantly their liver function with gluten withdrawal. Some of the patients in both groups had no apparent symptoms or signs suggesting CD. The authors emphasize that the early detection and treatment of CD may prevent the progression to end-stage liver failure. Therefore, CD must be screened in patients with autoimmune liver disease or hepatitis/cirrhosis of unknown etiology and in those undergoing liver transplantation. Moreover, an essential component of the clinical surveillance after transplantation in CD patients is the assessment of compliance with a gluten-free diet. The present case illustrates the association between CD and liver disease. Our patient was a young woman presenting with asymptomatic hypertransaminasemia. The initial CD screening was based on autoantibodies, followed by duodenal biopsy.

Sprayed or vaporised products generate aerosols that can result i

Sprayed or vaporised products generate aerosols that can result in potential inhalation exposure of consumers using the product. As those products with propellant producing foam or soft gels are not suspected to emit inhalable aerosol, they are excluded from our further discussion. As defined by the German MAK commission, aerosols are multiphase systems of particulate solids or liquids Antidiabetic Compound Library screening dispersed in gases such as air (Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area (MAK

commission, 2010)). Aerosols include dusts, fumes and mists. Dusts consist of particles of solid matter generated by a mechanical process, or particles which have been agitated and dispersed in gases. Fumes are dispersions of very finely distributed solid matter in gases. They arise from thermal processes (e.g., welding fumes, metal (oxide) fumes, soot and flue ash) or chemical processes (e.g., the reaction of ammonia with hydrogen chloride). Mists are finely divided liquid droplets of a substance or mixture suspended in air with sizes generally ranging from 2 μm to 100 μm. They arise during nebulisation of liquids, http://www.selleckchem.com/products/Romidepsin-FK228.html during condensation from the vapour phase and during chemical processes (e.g., oil mist, hydrogen chloride in damp air). Due to the anatomical construction

of the respiratory tract, with a brighter lumen in the upper trachea and very small ones in the alveolar region, particle size of aerosol is a relevant parameter for the distribution of substances in compartments of the respiratory tract. The final particle size of a product aerosol is determined by the used ingredients and packaging details (e.g., spray nozzle, can size, etc.). Aerosols can consist of a

wide spectrum of particle sizes, i.e. larger particle sizes (>10 μm), exposure to which is limited to the upper respiratory tract and tracheobronchial tree, but also respirable particle sizes (<10 μm) which can reach deep lung regions (U.S. Department of Labor, MSHA, 2006). Understanding of particle size distribution else is essential for risk assessment since there is broad consensus in the scientific community for the following assumptions: • Significant absorption of inhaled substances can occur in all parts of the respiratory tract. The most important aspects of deposition of inhaled particles are shown in Fig. 1. Typically, propellant gas sprays may produce proportionate respirable particles or droplets <10 μm particle size (Bremmer et al., 2006a and Eickmann, 2007a), whereas pump sprays emit larger droplets in a non-respirable range >10 μm particle size. As mentioned above the particle/droplet size distribution is complex and depends on product formulation and the technical details of the applicator. Thus, independent of the spray category, the particle/droplet size spectrum can be modified in order to generate an optimized particle size distribution.

, 2013) The reason for the high ikaite concentrations on the top

, 2013). The reason for the high ikaite concentrations on the top of sea ice should be the same as in the first case; the increase in ikaite concentration in the bottom of sea ice is probably caused by the increase in pH due to the photosynthetic activity. Brine pH has been reported

to be as high as 10 in sea ice (Gleitz et al., 1995). As a result, although the brine concentration in the bottom of sea ice is low due to the warm sea ice, the dramatic increase in brine pH due to the photosynthetic activity would greatly increase the CO32 − fraction thus enhancing the likelihood of ikaite precipitation in sea ice, even though the concentrations of Ca2 + and DIC are low due to relatively warmer sea ice. It is important to point out that in our experimental design, the solution Navitoclax cost pH was kept constant during the course of experiment. However, in natural sea ice, the precipitation of ikaite will lead to a decrease in pH, resulting in a decrease in solution supersaturation. As a consequence, the equilibrium between the solid phase and liquid phase could be established in a short time and thus the precipitation will cease until the equilibrium

is broken again by further concentration of brine solution and/or pH change. The effect of physico-chemical processes in sea ice on calcium carbonate precipitation was investigated. Ikaite (CaCO3·6H2O) is the only polymorph of calcium carbonate precipitated under all studied experimental conditions in artificial seawater (ASW), suggesting ICG-001 purchase that

ikaite is very likely the only polymorph of calcium carbonate formed in natural sea ice as well. PO4 is Glycogen branching enzyme crucial for ikaite formation in the NaCl medium. However, it is not important for ikaite formation under ASW conditions. pH is the controlling factor in ikaite precipitation due to its strong impact on CO32 − concentrations. Ionic strength has two opposite thermodynamic effects on ikaite precipitation, as the change in solution ionic strength affects the CO32 − concentrations and the activities of Ca2 + and CO32 − in opposite directions. The increase in ionic strength could also kinetically accelerate the ikaite nucleation rate. In ASW, the presence of inhibitor ions could strongly retard ikaite precipitation. The large variations in PO4 concentrations have no impact on ikaite precipitation, indicating that ikaite precipitation is neither thermodynamically nor kinetically affected by PO4. Gernot Nehrke is supported by the DFG by grant NE 1564/1-1 (SPP 1158). Yu-Bin Hu is the beneficiary of a doctoral grant from the AXA Research Fund. “
“The authors regret the corrections and wish to replace the below Supplementary material. “
“The authors regret the need for corrections and wish to replace the information below in the Supplementary material. Figure S1.

Approval from the Animal Experiment Committee of the University o

Approval from the Animal Experiment Committee of the University of Kuopio and the Provincial Government Vincristine research buy of Eastern Finland was obtained for all animal study plans. Following euthanasia, liver tissues were excised, sliced, and snap-frozen. The tissues were later homogenized and total RNA was extracted using Qiagen RNeasy kits according to the manufacturer’s instructions (Qiagen, Mississauga, Canada) as previously described (Boutros et al., 2011). The isolated RNA was assayed on Affymetrix RAT230-2 (Wis and F344; performed with six biological replicates each) or RAE230-A (L-E, H/W, LnA, and LnC; performed with four biological replicates each) arrays at The Centre for Applied Genomics at The

Hospital for

Sick Children (Toronto, Canada). The two platforms RAT230-2 and RAE230-A differ by the number of probe sets contained on the array. The platform RAE230-A is a subset of RAT230-2 and hence shares many of the same genes as RAT230-2. Our statistical comparisons were performed within the same platform; thus any variability is balanced and no bias is introduced. We rigorously assessed the technical quality of each array and none were excluded from subsequent data analyses. Animal handling and reporting comply with ARRIVE guidelines (Kilkenny et al., 2010). Raw quantitated array data (CEL files) were loaded into the R Enzalutamide price statistical environment (v2.12.2) using the affy package (v1.28.0) of the BioConductor library (Gentleman et al., 2004). Data were screened for spatial and distributional homogeneity and none were excluded from this study. Data were pre-processed with a sequence-specific version of RMA algorithm – GCRMA – as implemented in R (gcrma package v2.22.0). Probes were remapped to Entrez Gene IDs using rat2302rnentrezgcdf (v13.0.0) and rae230arnentrezgcdf STK38 (v13.0.0) R packages (Dai et al., 2005). Entrez Gene annotation was downloaded from NCBI on 2011-02-22. Individual strains were treated as separate cohorts and animals within a cohort were pre-processed together to avoid confounding effects from co-normalization of diverse strains. Raw and

pre-processed microarray data are available in the GEO repository under accession GSE31411. Following pre-processing, we employed general linear-modeling to identify genes affected by TCDD treatment relative to the vehicle control. The expression profiles across all animals within a cohort were determined using a per-gene linear model that assesses both basal levels and TCDD-induced effects. Coefficients were fit to terms representing each effect and the standard errors of the coefficients were adjusted using an empirical Bayes moderation of the standard error (Smyth, 2004). To test if each coefficient was statistically different from zero, we applied model-based t-tests, followed by a false-discovery rate adjustment for multiple-testing (Storey and Tibshirani, 2003).