Analysis of focal dermal hypoplasia-associated mutations in Porcn revealed that loss of enzymatic activity arises from altered stability. A consensus sequence within Wnt3a was identified (CXCHGXSXXCXXKXC) that contains residues that mediate Porcn binding, fatty acid transfer, and Wnt HM781-36B signaling. We also showed

that Ser or Thr, but not Cys, can serve as a fatty acylation site in Wnt, establishing Porcn as an O-acyltransferase. This analysis sheds light into the mechanism by which Porcn transfers fatty acids to Wnt proteins and provides insight into the mechanisms of fatty acid transfer by MBOAT family members.”
“Objectives: We aimed to establish community-based normal reference values of 24-h ambulatory blood pressure monitoring (ABPM) for Chinese children and adolescents. Furthermore, we investigated how excluding overweight children affects BP percentiles and compared them with German references. Methods: In this territory-wide cross-sectional prospective cohort study, 1445 Hong Kong Chinese children and adolescents aged 8-17 years with body height between 119 and 185cm were recruited. Their ABPM assessment was performed using validated arm oscillometric recorders (A&D TM-2430) and complied with American Heart Association’s recommendations. The reference tables were constructed using the LMS method

to normalize skewed distribution of ABP data to sex and age or height. Results: The ambulatory BP

was higher among boys and the difference between boys and girls progressively widened with age. An increasing trend buy CCI-779 in daytime and night-time SBP and DBP with age and height was observed in both sexes. The age-specific and sex-specific 95th percentiles from nonoverweight children (n=1147; 79%) were lower than the whole cohort by up to 2.5 and 1mmHg for SBP and DBP, respectively. In comparison, our overall and nonoverweight reference standards were generally higher than corresponding German references. Conclusion: The study provides ambulatory BP standards for Chinese AC220 in vitro children, with sex-related age-specific and height-specific percentiles. Further longitudinal studies are required for investigating its clinical utility in Chinese.”
“Our aim was to use the fuzzy analytic hierarchy process approach to prioritize the factors that influence nurses’ satisfaction with a hospital information system. First, we reviewed the related literature to identify and select possible factors. Second, we developed an analytic hierarchy process framework with three main factors (quality of services, of systems, and of information) and 22 subfactors. Third, we developed a questionnaire based on pairwise comparisons and invited 10 experienced nurses who were identified through snowball sampling to rate these factors. Finally, we used Chang’s fuzzy extent analysis method to compute the weights of these factors and prioritize them.

\n\nSignificance and Impact of the Study: Fer-1 mouse This study was the first to investigate

the proportion of living and dead bacteria within a stationary colony quantitatively.”
“Background: The analgesic co-proxamol (paracetamol/dextropropoxyphene combination) has been widely involved in fatal poisoning. Concerns about its safety/effectiveness profile and widespread use for suicidal poisoning prompted its withdrawal in the UK in 2005, with partial withdrawal between 2005 and 2007, and full withdrawal in 2008. Our objective in this study was to assess the association between co-proxamol withdrawal and prescribing and deaths in England and Wales in 2005-2010 compared with 1998-2004, including estimation of possible substitution effects by other analgesics.\n\nMethods and Findings: We obtained prescribing data from the NHS Health and Social Care Information Centre (England) and Prescribing Services

Partneriaeth Cydwasanaethau GIG Cymru (Wales), and mortality data from the Office for National Statistics. We carried out an interrupted time-series analysis of prescribing and deaths (suicide, open verdicts, accidental poisonings) involving single analgesics. The reduction in prescribing of co-proxamol following its withdrawal in 2005 was accompanied by increases in prescribing of several other analgesics (co-codamol, paracetamol, codeine, co-dydramol, tramadol, Pevonedistat oxycodone, and morphine) during 2005-2010 compared with 1998-2004. These changes GSK1210151A research buy were associated with major reductions in deaths due to poisoning with co-proxamol receiving verdicts of suicide and undetermined cause of -21 deaths (95% CI -34 to -8) per quarter, equating to approximately 500 fewer suicide deaths (-61%) over the 6 years 2005-2010, and -25 deaths (95% CI -38 to -12) per quarter, equating to 600 fewer deaths (-62%) when accidental poisoning deaths were included. There was little

observed change in deaths involving other analgesics, apart from an increase in oxycodone poisonings, but numbers were small. Limitations were that the study was based on deaths involving single drugs alone and changes in deaths involving prescribed morphine could not be assessed.\n\nConclusions: During the 6 years following the withdrawal of co-proxamol in the UK, there was a major reduction in poisoning deaths involving this drug, without apparent significant increase in deaths involving other analgesics.”
“We demonstrate the scarcity of conserved bacterial-type promoters in plastids of Streptophyta and report widely conserved promoters only for genes psaA, psbA, psbB, psbE, rbcL.

napus (BnBP), Brassica rapa L. (BrBP), and Brassica oleracea L. (BoBP). These Brassica orthologs show a high degree of conservation at the nucleotide and amino acid level, including the homeodomain and the intron positions. The B. napus ortholog complemented the Arabidopsis bp null allele and overexpression Selleckchem Baf-A1 of BnBP in B. napus transgenic lines resulted in altered leaf phenotypes. Together, these results suggest that Brassica BP genes are functional orthologs

of Arabidopsis BP. Ectopic expression of AS2, a negative regulator of BP encoding a LOB domain transcription factor, in transgenic B. napus produced compact inflorescence architecture reminiscent of the loss-of-function bp mutant phenotype described previously in Arabidopsis. These results provide evidence in support of BP as a potential target gene for modifying inflorescence

architecture in Brassica crop species.”
“A thoughtful treatment algorithm is required to optimally treat distal tibia nonunion. A healthy respect for the tenuous soft tissue envelope, compromised vascularity, and challenging mechanical environment is advisable. Achieving osseous union and improved functionality requires an individualized plan of care based on the personality of the nonunion and host. Attention must be focused on providing mechanical selleck compound stability at the site of nonunion and providing biologic supplementation.”
“INTRODUCTION Diagnostic laparoscopy with appendicectomy (LA) has become the accepted method of investigation and treatment of appendicitis. However, concerns remain in cases of complicated appendicitis when many advocate conversion to an open procedure (LCOA) owing to the risk of complications. The aim of this study was to look for factors that could predict complications occurring Selleck Y27632 in patients undergoing

appendicectomy. METHODS Data inclusive of all consecutive appendicectomies over a two-year period were retrieved from the computerised theatre database. Clinical details including admission inflammatory markers, complications, severity (final pathology) and length of stay were collected from the discharge letter. Readmissions were identified as those hospital identifiers had a second set of admission dates and/or a second discharge letter. RESULTS During the 2-year study period, 517 appendicectomies were performed. Of these, 429 patients (83%) had LA and the remaining 88 (17%) had LCOA. The LA group had a mean age of 28 years (range: 2-86 years) and a mean C-reactive protein (CRP) level of 71mg/l (range: 0-480mg/l) while the LCOA group had a mean age of 46 years (range: 11-92 years) and a mean CRP level of 162mg/l (range: 3-404mg/l). These differences in age and CRP were significant (p smaller than 0.001). LA patients were less likely to have complications overall (22% vs 52%, p=0.015).

\n\nOverall 131 suspected NET cases were included. The most common condition considered suspicious for NET CDK assay was the increase of blood markers (66), followed by inconclusive findings at conventional imaging (CI, 41), clinical signs/symptoms (10), equivocal F-18-fluorodeoxyglucose (FDG) PET (7) or somatostatin receptor scintigraphy (SRS, 4), or a combination of the above (3). PET/CT results were true-positive in 17 cases, true-negative in 112 and false-negative in 2 (overall sensitivity 89.5 %, specificity 100 %). Interestingly, increased blood markers and clinical signs/symptoms were associated with the lowest frequency of true-positive findings (1/66 and 1/10, respectively),

while CI findings were confirmed in one third of the cases (13/41).

Overall, the incidence of NET in the studied population was 14.5 % (19/131).\n\nOur data confirm the good accuracy (98 %) of Ga-68-DOTA-NOC PET/CT in NET lesion detection. However, our results also suggest that Ga-68-DOTA-NOC PET/CT may not be routinely recommended in patients with a suspicion of NET based on the mere detection of increased blood markers or clinical symptoms. Positive CI alone or in association with clinical/biochemical findings is on the contrary associated with a higher probability of true-positive findings.”
“Despite the increased use of complementary and alternative medicine (CAM) by breast cancer patients, there is little published information regarding CAM use in the Scottish breast cancer population.\n\nA questionnaire comprising five sections-demographics; PR-171 perceived health GSK126 in vitro status, prescribed medicines; use, indications, satisfaction and expenditure on CAMs; attitudes towards and factors associated with CAM use; and attitudinal statements-was issued to patients attending the Aberdeen Breast Clinic.\n\nA total of 453

questionnaires were distributed and 360 (79.5%) returned. Respondents were prescribed a mean of 3.2 medicines (95% CI 2.83-3.47). With regard to CAM use, 33.1% of respondents reported current use, 36.4% prior use, and 30.6% reported never having used CAMs. The key indications for use were general well being, boosting immune system and cancer prophylaxis, with high levels of satisfaction reported. The strongest association for CAM use was use by friends and family and higher educational attainment (p < 0.001). Supplements with estrogenic activity, such as soya or red clover, were taken by 29% of respondents. Herbs (echinacea, pomegranate, peppermint, chamomile, grapefruit, garlic, ginseng) that have the potential to interact with adjuvant endocrine therapies (tamoxifen, anastrazole, letrozole, exemestane) were being taken by 38% of treated patients.\n\nThe level of CAM use by Scottish breast cancer patients is similar to that reported from other countries, although there are marked differences in the type, nature and frequency of specific CAM therapies.

Digital radiographs were taken with the same dose as well as with

half the dose used for the conventional radiographs. A total of 20 Burmese pythons (Python molurus) were examined in dorsoventral and lateral projection. Four criteria (three features, one overall assessment) were defined for each of the anatomical structures lung, trachea and spinal column and assessed by five veterinarians in a semi-blinded BMS-777607 order study using a score system. Comparison of the ratings between the techniques used was done using a visual grading analysis. For the lung, two of the three features as well as the overall assessment were rated significantly superior using the digital system. The trachea was rated significantly superior using the conventional

system for the overall assessment as well as for one feature. For the spinal column, the overall assessment was significantly superior using the digital system with the full dose. Conventional radiography as well as digital radiography using half the dose was rated significantly inferior for one feature each. The study demonstrates the advantage of the digital technique for the assessment of the relatively low-contrast respiratory tract. A limiting factor is the demonstration of particularly small structures. Generally, a dose reduction (compared to a conventional high-resolution film-screen-system) is possible for the evaluation of the respiratory system.”
“Background This is an ecological study that examines the relationship between antiviral drug collection this website during the 2009/2010 A/H1N1

OSI-906 inhibitor influenza pandemic, and area-level ethnicity, socioeconomic deprivation and distance from an antiviral collection point (ACP).\n\nMethods Age-standardized antiviral collection rates (ACR) were calculated for each super output area (geographic areas representing a population of approximate to 1500) in Sandwell, UK for all residents who received an antiviral drug for influenza-like illness between 23 July 2009 and 7 February 2010. Multivariable regression was used to examine the relationship between ACR and ethnicity (percentage population non-white), socioeconomic deprivation (index of multiple deprivation, IMD) and distance from an ACP.\n\nResults Socioeconomic deprivation, ethnicity and distance from an ACP were independently associated with a reduction in ACR. Each one-point increase in the IMD score was associated with a drop in the ACR of 15.7 prescriptions per 100 000 population (P 0.013).\n\nConclusions Socioeconomic deprivation, ethnicity and distance from an ACP may have influenced health-seeking behaviour during the 2009/2010 influenza pandemic. This suggests possible inequalities in access to antivirals during the most recent influenza pandemic. Qualitative research is needed to examine the reasons for this. Individual-level data on ethnicity should be routinely collected in the event of a future pandemic.

Therefore, there is a growing need for innovative therapies and techniques for monitoring and prevention of this disease. The exact cause of most ovarian tumors usually remains unknown. Ovarian cancer is believed to be caused by a range of different variables. This review is an attempt to summarize some genetic factors involved in the

disruption of certain signaling pathways responsible for ovarian tumor transformation and development. Those factors considerably contribute to accurate diagnostics, treatment and prognosis in ovarian cancer.”
“Aims/hypothesis End-stage renal disease (ESRD) patients with diabetes have been regarded as being at the highest risk of cardiovascular disease. We therefore investigated see more the relationship between diabetes and the Fosbretabulin Cytoskeletal Signaling inhibitor incidence of peripheral artery disease (PAD) in new

haemodialysis patients.\n\nMethods We enrolled 1,513 ESRD patients who had just begun haemodialysis therapy. They were divided into two groups: those with (n=739) and those without diabetes (n=774). The endpoint was the development of PAD, defined as ankle brachial pressure index <= 0.9 or toe brachial pressure index <0.7 in patients with an ankle brachial pressure index >0.9.\n\nResults According to the Kaplan-Meier method, the 10 year event-free rate for development of PAD and lower limb amputation was significantly lower in the diabetes group than in the non-diabetes group (60.3% vs 82.8%, HR 2.99, 95% CI 2.27, 3.92, p<0.0001 and 93.9% vs 98.9%, HR 5.59, 95% CI 2.14, 14.7, p=0.0005 for PAD and lower limb amputation, respectively). In patients with diabetes, quartile analysis of HbA(1c) levels showed that the highest quartile group (>= 6.8% [51 mmol/mol]) had significant development of PAD and lower limb amputation compared with lower quartile groups

(PAD HR 1.63, 95% CI 1.17, 2.28, p=0.0038; lower limb amputation HR 2.99, 95% CI 1.17, 7.70, p=0.023).\n\nConclusions/interpretation Diabetes was a strong predictor of PAD after initiation of haemodialysis therapy in patients with ESRD. In addition, HSP990 price higher HbA1c levels were associated with increased risk of developing PAD and requiring limb amputation in such diabetic populations.”
“Determining whether a conflict between gene trees and species trees represents incomplete lineage sorting (ILS) or hybridization involving native and/or invasive species has implications for reconstructing evolutionary relationships and guiding conservation decisions. Among vertebrates, turtles represent an exceptional case for exploring these issues because of the propensity for even distantly related lineages to hybridize. In this study we investigate a group of freshwater turtles (Trachemys) from a part of its range (the Greater Antilles) where it is purported to have undergone reticulation events from both natural and anthropogenic processes.

Whole-body irradiation also induced myeloablation and chimerism in tissues, and induced the entry of transplanted cells into the small intestine and liver. This result demonstrates that grafted BM cells or GFP(+)lin(-)Sca-1(+) cells are not transient in the GIT. Thus, these transplanted cells could be used for the long-term treatment of various pathologies or as a one-time treatment option if myeloablation-induced chimerism alone is not sufficient to induce

the entry of transplanted cells into non-haematopoietic tissues.”
“Objective:We sought to determine lesion sites and spatial lesion patterns in spontaneous anterior interosseous nerve syndrome (AINS) with high-resolution BKM120 concentration magnetic resonance neurography (MRN).Methods:In 20 patients with AINS and 20 age- and sex-matched controls, MRN of median nerve fascicles was performed at 3T with large longitudinal anatomical coverage (upper arm/elbow/forearm): 135 contiguous axial slices (T2-weighted: echo time/repetition time 52/7,020 ms, time of mTOR inhibitor acquisition: 15 minutes 48 seconds, in-plane resolution: 0.25 x 0.25 mm). Lesion classification was performed by visual inspection and by quantitative analysis of normalized T2 signal

after segmentation of median nerve voxels.Results:In all patients and no controls, T2 lesions of individual fascicles were observed within upper arm median nerve trunk and strictly followed a somatotopic/internal topography: affected were those motor fascicles that will form the anterior interosseous nerve further distally while other fascicles were spared. Predominant lesion focus was at a mean distance of 14.6 5.4 cm proximal to the humeroradial joint. Discriminative power of quantitative T2 signal analysis and of qualitative lesion rating was high, with 100% sensitivity and 100% specificity (p smaller than 0.0001). Fascicular T2 lesion patterns were rated as multifocal (n = 17), monofocal (n = 2), or indeterminate (n = 1) by 2 independent observers with strong agreement (kappa = 0.83).Conclusion:It has been difficult to prove the existence of fascicular/partial nerve

lesions in spontaneous neuropathies using clinical and electrophysiologic findings. With MRN, fascicular lesions with strict somatotopic organization were observed in upper arm median nerve trunks of patients GSK461364 molecular weight with AINS. Our data strongly support that AINS in the majority of cases is not a surgically treatable entrapment neuropathy but a multifocal mononeuropathy selectively involving, within the main trunk of the median nerve, the motor fascicles that continue distally to form the anterior interosseous nerve.”
“The aim of this work is to cast some light on the H-bonds in double-stranded DNA in its AI and BI forms. For this purpose, we have performed the MP2 and DFT quantum chemical calculations of the canonical nucleoside conformers, relative to the AI and BI DNA forms, and their Watson-Crick pairs, which were regarded as the simplest models of the double-stranded DNA.

Mutational analysis was performed P5091 cost using a multiplexed polymerase chain reaction genotyping platform to query for hotspot

mutations in the genes IDH1 at codon R132. IDH1-negative cases underwent Sanger sequencing of IDH2 exon 4. No osteosarcomas (0/36) and 61% of chondrosarcomas (14/23) harbored a somatic mutation in IDH1/2, with the majority (86%) of mutations found in the IDH1 gene. IDH1/2 mutation analysis appears to be a promising biomarker for the distinction of chondrosarcoma from chondroblastic osteosarcoma. A positive result strongly favors the diagnosis of chondrosarcoma over chondroblastic osteosarcoma. The presence of IDH1/2 mutations can also help confirm the diagnosis of dedifferentiated chondrosarcoma when the tumor displays osteosarcomatous differentiation.”
“The objective of this study was to investigate the effect of rhein lysinate (RHL) on monocyte adhesion and its

mechanism. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to determine the growth inhibition by drugs. The monocyte chemoattractant protein (MCP)-1 levels were assayed using MCP-1 ELISA. The expression of proteins was detected by Western blotting analysis. The results indicated that RHL inhibited monocyte adhesion in a dose- and time-dependent manner. RHL (< 20 mu mol/L) and lipopolysaccharide (LPS) had no effect on viability of human umbilical vein endothelial Selleckchem KU-57788 cells. Therefore, 20 mu mol/L RHL BIX 01294 solubility dmso was selected for this study. RHL inhibited secretion of MCP-1 induced

by LPS and expression of intercellular adhesion molecule (ICAM)-1 and vascular cell adhesion molecule (VCAM)-1. In the meantime, both RHL and p38 inhibitor (SB203580) inhibited phosphorylation of p38 and mitogen-activated protein kinase-activated protein kinase-2 (MAPKAPK-2) and transcription and expression of ICAM-1 and VCAM-1. In conclusion, RHL inhibits the transcription and expression of ICAM-1 and VCAM-1 by the p38/MAPKAPK-2 signaling pathway, and the effect of RHL on transcription and expression of ICAM-1 and VCAM-1 is similar to p38 inhibitor. RHL could be a prophylactic drug for atherosclerosis.”
“The voltage-dependent anion channel (VDAC) and the adenine nucleotide translocase (ANT) have central roles in mitochondrial functions such as nucleotides transport and cell death. The interaction between VDAC, an outer mitochondrial membrane protein and ANT, an inner membrane protein, was studied in isolated mitochondria and in vitro. Both proteins were isolated from various mitochondrial sources and reconstituted in vitro using a biomimetic system composed of recombinant human VDAC isoform 1 (rhV-DAC1) immobilized on a surface plasmon resonance (SPR) sensor chip surface.

In patients referred for ICA, an ischemic etiology was assumed in the presence of bigger than = 75% stenosis in two or more epicardial vessels or bigger than = 75% stenosis in the left

main or proximal left anterior descending artery. Results: During this period 100 patients (mean age 57.3+/-10.5 years, 64% men) with HF and systolic dysfunction were referred for MDCT to Alisertib exclude CAD. Median effective radiation dose was 4.8 mSv (interquartile range 5.8 mSv). Mean LVEF was 35+/-7.7% (range 20-48%) and median CAC score was 13 (interquartile range 212). Seven patients were in atrial fibrillation. Almost half of the patients (40%) had no CAC and none of these had significant stenosis on CIA. In an additional group of 33 patients CIA was

able to confidently exclude obstructive CAD. Twenty-seven patients were classified as positive for CAD (16 due to CAC bigger than 400 and 11 with bigger than = 50% stenosis) and were associated with lower LVEF (p=0.004). Of these, 21 patients subsequently underwent ICA: obstructive CAD was confirmed in nine and only six had criteria for ischemic cardiomyopathy. Conclusion: In our HF population, MDCT was able to exclude an ischemic etiology in 73% of cases in a single test. According to our results the Agatston calcium score may serve as a gatekeeper for CTA in patients with HF, with a calcium score of zero confidently excluding an ischemic etiology. (C) 2013 find more Sociedade Portuguesa de Cardiologia. Published by Elsevier Espana, S.L.U. All rights reserved.”
“Cladonia maculata, C. paranaensis and C. quiririensis

are described as new to science. These species LBH589 order were found between the altitudes of 900 to 1887 meters on the Serra do Mar Mountain in Southern Brazil.”
“Background:\n\nLong-term alcohol consumption alone did not cause chronic pancreatitis (CP) but impaired exocrine pancreatic function. This study is to explore the reversibility of exocrine pancreatic insufficiency in the abstinent rats and its mechanism.\n\nMethods:\n\nForty-eight healthy male Wistar rats were divided randomly into 4 groups: 6-month control, 6-month ethanol, 9-month control, and 9-month ethanol + withdrawal. Morphological changes of pancreatic acinar cells were observed. Pancreatic amylase and lipase were measured using an automatic biochemical analyzer. Free fatty acid (FFA) in rat intestinal chyme was measured. Cholecystokinin (CCK) levels were determined by radioimmunoassay. The expression of CCK-A receptors was quantitatively analyzed by Western blot.\n\nResults:\n\nAlcohol-induced ultramicrostructure changes of pancreatic acinar cells, including lipid droplets, myelinoid inclusion bodies, dilated rough endoplasmic reticulums, and diminished zymogen granules, were not attenuated after alcohol abstinence.

The mechanism of islet regeneration remains poorly understood, but the identification of islet progenitor sources is critical for understanding beta-cell regeneration. One potential source is the islet proper, via the dedifferentiation, proliferation, and redifferentiation of facultative progenitors residing within the islet. Neogenesis, or that the new pancreatic

islets can derive from progenitor cells present within the ducts has been reported, but the existence and identity of the progenitor cells have been debated.\n\nIn this review, we focus on pancreatic ductal cells, which are islet progenitors capable of differentiating into islet beta-cells. Islet neogenesis, https://www.selleckchem.com/products/kpt-8602.html seen as budding of hormone-positive cells from the ductal epithelium, is considered to be one mechanism for normal islet growth after birth and in regeneration, and has suggested the presence of pancreatic stem cells. Numerous results support the neogenesis hypothesis, the evidence for the hypothesis in the adult comes primarily from morphological

studies that have in common the production of damage to all or part of the pancreas, with consequent inflammation and repair. Ro-3306 nmr Although numerous studies support a ductal origin for new islets after birth, lineage-tracing experiments are considered the “gold standard” of proof. Lineage-tracing experiments show that pancreatic duct cells act as progenitors, giving rise to new islets U0126 ic50 after birth and after injury. The identification of differentiated pancreatic ductal cells as an in vivo progenitor for pancreatic beta-cells has implications for a potentially important, expandable source of new islets for diabetic replenishment therapy. (C) 2009 Elsevier Inc. All rights reserved.”
“Background: Little is known about psychological risk factors in cerebrovascular disease. We examined the association between psychological distress and risk of death due to cerebrovascular disease.\n\nMethods:

We obtained data from 68 652 adult participants of the Health Survey for England (mean age 54.9 [standard deviation 13.9) yr, 45.0% male sex) with no known history of cardiovascular diseases at baseline. We used the 12-item General Health Questionnaire (GHQ-12) to assess the presence of psychological distress. We followed participants for eight years for cause-specific death using linkage to national registers.\n\nResults: There were 2367 deaths due to cardiovascular disease during follow-up. Relative to participants with no symptoms of psychological distress (GHQ-12 score 0) at baseline, people with psychological distress (GHQ-12 score 4, 14.7% of participants) had an increased risk of death from cerebrovascular disease (adjusted hazard ratio [HR] 1.66, 95% confidence interval [CI] 1.32-2.08) and ischemic heart disease (adjusted HR 1.59, 95% CI 1.34-1.88). There was also evidence of a dose response effect with increasing GHQ-12 score (p for trend < 0.001 in all analyses).