Miracle-dz/UniFAR-FTUs huggingface dataset:
Tolerability of fluoropyrimidines appears to differ by region.

3514 Background: Limited information is available regarding regional differences in tolerability for fluoropyrimidines. This is an initial assessment of the Roche phase III databases on patients treated for metastatic colorectal cancer (MCRC) and adjuvant colon cancer. METHODS Retrospective multivariate analyses (logistic regression) were performed using pooled data from two identical studies (n=1189) in MCRC comparing capecitabine (X) monotherapy with i.v. 5-FU/LV (Mayo regimen) [Hoff et al. and Van Cutsem et al. JCO 2001], and from an adjuvant study (n=1861) comparing XELOX (X+oxaliplatin) with either the Mayo or Roswell Park 5-FU/LV regimens [Schmoll et al. ASCO 2005]. Treatment-related safety parameters evaluated were: all grade 3/4 AEs, grade 3/4 GI events (diarrhea, nausea, vomiting, stomatitis), and grade 3/4 neutropenia events (febrile neutropenia, neutropenia reported as AE or lab value). Dependent variables for 1st-line MCRC data were: US vs. non-US; and for adjuvant colon cancer: US vs. non-US, US vs. Asia, and RoW (rest of the world) vs. Asia. Factors in the adjusted relative risk model were: age, gender, PS, BSA, BMI, baseline creatinine clearance and treatment (X vs. 5-FU/LV; XELOX vs. Mayo vs. RP). RESULTS Region was significantly associated with grade 3/4 AEs and grade 3/4 GI events in both settings ( table ). There were no relevant interactions between region and type of fluoropyrimidine treatment. Reporting of grade 3/4 neurosensory toxicity was similar in the US and outside US. CONCLUSIONS Differences in the rates of grade 3/4 toxicity were significantly associated with the region of the world in which the patients were treated. Patients treated in the US experienced the highest rates of grade 3/4 toxicity (see table ). This difference was observed for both X and for 5-FU. The reasons for these differences remain to be elucidated. Acknowledgements: C. Allegra, J. Bertino, J-Y Douillard, B. Gustavsson, G. Milano, M. O'Connell, Y. Rustum, J. Tabernero, J. Fagerberg, F. Gilberg, and F. Sirzen. [Table: see text] [Table: see text].
The patterns of small bowel motility: physiology and implications in organic disease and functional disorders

The physiology and pathophysiology of small bowel motility are reviewed with particular focus on the motility patterns and periods that are detected by intraluminal manometry. Motility patterns are groups of phasic pressure waves resulting from contractions of the circular muscle layer of the small bowel that are organized by the enteric nervous system. Phase III of the migrating motor complex, the hallmark of the fasting motility period, thus reflects enteric neuromuscular function. Response to meal challenge also involves the CNS, reflexes beyond the gut and endocrine responses. Although specific disease diagnosis cannot be made by motility studies of the small bowel, the functional integrity is revealed. The normal occurrence of the essential patterns and periods of motility and the absence of distinctly abnormal patterns evidence preserved function, whereas the opposite indicates clinically significant dysmotility. Certain motility patterns are occasionally seen both in health and disease, and increased prevalence indicates a moderate dysfunction of yet unclear significance. Bacterial overgrowth with Gram‐negative bacilli is the consequence of severe small bowel dysmotility, and a diagnosis that can be predicted by a motility study. Testing can be useful in the clinical management of paediatric and adult patients also by predicting the prognosis and response to enteral nutrition and medical therapy. Further studies are, however, needed to take full advantage of motility testing in clinical practise.
Stable, Long‐Term Bacterial Production of Soluble, Dimeric, Disulfide‐Bonded Protein Pharmaceuticals without Antibiotic Selection

Numerous biopharmaceuticals and other recombinant biotechnology products are made in prokaryotic hosts. However, bacterial production of native, biologically active eukaryotic proteins is rarely possible for disulfide‐bonded and/or multisubunit proteins. We previously described the production of soluble, native disulfide‐bonded dimeric proteins in the Escherichia coli cytoplasm (Miele et al., 1990; Mantile et al., 1993). Native, biologically active proteins with up to six disulfide bonds have been produced with our expression system (Garces et al., 1997). However, plasmid instability during induction limited its usefulness. We now report the stable, high‐level expression of soluble, disulfide‐bonded human uteroglobin without antibiotic selection. We designed a new vector containing a multifunctional stabilization region that confers complete plasmid stability and increased protein yields without copy number increases. Recombinant expression remains fully inducible after long‐term continuous culture in nonselective liquid medium (at least 260 generations). This system may significantly expand the applications of bacterial expression to recombinant production of soluble, bioactive proteins for biochemical studies and biopharmaceutical/industrial purposes. As a result of the very broad activity spectrum of the stabilization region we selected, its use could be extended to bacterial hosts other than enterobacteria.
Changes in adhesive properties of epithelial cells during early morphogenesis of the mammary gland

Previous studies have demonstrated that cell adhesion systems are downregulated in epithelial buds at the earliest stages of submandibular gland and hair follicle development, but are restored at subsequent stages. Here it is shown that epithelial cell adhesion systems are also remodeled during early mammary gland development. Immunofluorescence and electron microscopy of the mouse mammary bud demonstrated that cell–cell adhesion systems were hardly detectable, with significant downregulation of expression of desmosomal molecules, but not of E‐cadherin and β‐catenin. Hemidesmosomal structures were also rarely found, although their component molecules were expressed. Differences in cell adhesivity between cells of the mammary bud and those of the overlying epidermis were shown by the finding that the mammary cells formed smaller aggregates than the epidermal cells and were not randomly mixed with the epidermal cells. At subsequent stages, the mammary epithelium restored cell–cell adhesion systems along with de novo expression of tight junction molecules. These data, together with previous findings, indicate that remodeling of epithelial cell adhesion systems is a general feature underlying the early development of several ectoderm‐derived organs and support the idea that segregation and rearrangements of cells are involved in early epithelial morphogenesis.
Autonomic nerve antibodies and autonomic nerve function in Type 1 and Type 2 diabetic patients

Abstract. Complement‐fixing adrenal medulla (CF‐ADM), sympathetic ganglion (CF‐SG), and vagal (CF‐V) nerve antibodies were determined in diabetic patients. Among 74 patients with Type 1 diabetes, CF‐ADM was detected in 7 (10%) cases, CF‐SG in 14 (19%) cases, and CF‐V in 8 (11%) cases. Among 38 patients with Type 2 diabetes, CF‐ADM was detected in 5 (13%) cases, CF‐SG in 4 (11%) cases, and CF‐V in 6 (16%) cases. There were associations between autonomic nerve antibodies and autonomic nerve function. CF‐ADM and/or CF‐SG were significantly (P < 0.002) less prevalent in Type 1 diabetic patients with autonomic neuropathy than in those without [5/44 (11%) vs. 14/30 (47%)] and, in agreement with this, the brake index, a sign of parasympathetic and sympathetic autonomic nerve function, was significantly (P < 0.005) higher (more normal) in these patients (–0.56 ± 0.13 vs. –1.04 ± 0.12). In Type 2 diabetic patients, the E/I ratio, an index of parasympathetic nerve function, was significantly (P < 0.03) lower (more abnormal) in those with CF‐V than in those without (–1.81 ± 0.17 vs. –1.20 ± 0.11). In conclusion, the frequency of sympathetic nerve antibodies was decreased in Type 1 diabetic patients with autonomic neuropathy, while in Type 2 diabetic patients parasympathetic nerve antibodies were related to severe parasympathetic neuropathy.
Skeletal muscle lipid peroxidation and insulin resistance in humans.

OBJECTIVE The relationships among skeletal muscle lipid peroxidation, intramyocellular lipid content (IMCL), and insulin sensitivity were evaluated in nine insulin-sensitive (IS), 13 insulin-resistant (IR), and 10 adults with type 2 diabetes (T2DM). DESIGN Insulin sensitivity was assessed by hyperinsulinemic-euglycemic clamp [glucose disposal rate (GDR)]. Lipid peroxidation was assessed by 4-hydroxynonenal (HNE)-protein adducts and general oxidative stress by protein carbonyl content. All patients were sedentary. RESULTS Protein-HNE adducts were elevated 1.6-fold in T2DM compared with IS adults, whereas IR showed intermediate levels of HNE-modified proteins. Protein-HNE adducts correlated with GDR, waist circumference, and body mass index. IMCL was increased by 4.0- and 1.9-fold in T2DM and IR patients, respectively, compared with IS, and was correlated with GDR and waist circumference but not BMI. Protein carbonyls were not different among groups and did not correlate with any of the measured variables. Correlations were detected between IMCL and protein-HNE. CONCLUSION Our data show for the first time that skeletal muscle protein-HNE adducts are related to the severity of insulin resistance in sedentary adults. These results suggest that muscle lipid peroxidation could be involved in the development of insulin resistance.
National Health Interview Survey mortality among US farmers and pesticide applicators.

BACKGROUND The mortality experience of pesticide-exposed workers across the US has not been thoroughly studied. METHODS Cox regression mortality analyses adjusted for the complex sample survey design were performed on mortality-linked 1986-1994 National Health Interview Survey (NHIS) data. RESULTS Nine thousand four hundred seventy-one farmers and pesticide applicators with 571 deaths were compared to 438,228 other US workers with 11,992 deaths. Age-adjusted risk of accidental death, as well as cancers of the nervous and lymphatic/hematopoietic systems, was significantly elevated in male and female pesticide-exposed workers; breast, prostate, and testicular cancer mortality risks were not elevated. CONCLUSIONS Compared to all other workers, farmers and pesticide applicators were at greater risk of accidental mortality. These pesticide-exposed workers were not at an increased risk of cancers possibly associated with exposure to estrogen analogue compounds, but were at an increased risk of hematopoietic and nervous system cancers. NHIS mortality follow-up represents an important occupational health surveillance instrument.
Specific changes in n -6 fatty acid metabolism in patients with chronic intestinal failure.

BACKGROUND AND AIMS In patients presenting severe malabsorption, essential fatty acid (EFA) deficiency can be corrected by intravenous lipids, but EFA abnormalities persist. The purpose of this study was to evaluate the role of large resection of the small bowel or malabsorption on plasma phospholipid EFA profile. METHODS The plasma phospholipid EFA composition was measured by gas chromatography in home parenteral nutrition patients with (n=13) or without small bowel resection (n=7) and in 14 healthy subjects. RESULTS The two groups of patients had the same nutritional status and comparable amounts of intravenous fat. In both groups, plasma fatty acid concentrations were significantly different from those observed in healthy subjects without EFA deficiency. Among them: a decrease in 18:2n -6, 22:5n -3, 22:6n -3 and an increase in 18:3n -3, 20:4n -6, 22:4n -6. Moreover, arachidonic acid to linoleic acid ratio was higher in both groups of patients, suggesting a stimulation of the elongation and desaturation of 18:2n -6. In multiple linear regression, 18:2n -6 and 20:4n -6 levels were not associated with the small bowel length, only 22:6n -3 concentration was correlated with small bowel length. CONCLUSIONS The patients with chronic intestinal failure on home parenteral nutrition presented specific change in their EFA and an increase in the n -6 fatty acid pathway. This could be related to the severe malabsorption.
AEROMEDICAL EVACUATION

Introduction Evacuation of injured personnel using rotary or fixed-wing aircraft has revolutionized the rapid transport of casualties from areas where there is either inadequate or no care available, to medical treatment facilities (MTFs) where essential and/or definitive care can be rendered. Although use of an aircraft can decrease transport time, the aeromedical environment creates unique stresses on the injured patient. The following are terms that describe evacuation of patients using aircraft.  Casualty evacuation (CASEVAC) is the movement of a casualty from the point of injury to medical treatment by nonmedical personnel. Casualties transported under these circumstances may not receive en route medical care. Typically , this involves a helicopter returning from the battlefield.  Medical evacuation (MEDEVAC) is the timely, efficient movement and en route care provided by medical personnel to the wounded being evacuated from the battlefield to MTFs using medically equipped vehicles or aircraft. Examples include civilian aeromedical helicopter services and Army air ambulances. This term also covers the transfer of patients from the battlefield to an MTF or from one MTF to another by medical personnel, such as from ship to shore.  Aeromedical evacuation (AE) generally utilizes US Air Force (USAF) fixed-wing aircraft to move sick or injured personnel within the theater of operations (intratheater) or between two theaters (intertheater), such as moving a casualty from Afghanistan to Germany. This is a regulated system in which care is provided by AE crewmembers. The AE crews may be augmented with Critical Care Air Transport Teams (CCATTs) to provide ICU level care.
Socially Networked Heterogeneity: The Influence of WhatsApp as a Social Networking Site on Polarisation in Kenya

Abstract Using a cross-sectional survey of two sampled counties in Kenya, this article analyses whether social networking sites reflect social network heterogeneity. It then examines how social network heterogeneity influences polarisation in Kenya. Three types of polarisation are examined: party, ethnic and ideological (around county resources). The study focuses specifically on the public WhatsApp platform (the most popular SNS in Kenya). To assess this empirical data, theoretical perspectives are drawn from the literatures on incidental and selective exposure and their impact on political polarisation. The findings indicate that the randomised composition of a WhatsApp group through public links indeed reflects social network heterogeneity. The findings further show that posting political news, obtaining political news and commenting on political news influence social network heterogeneity to some degree. This social network heterogeneity was also found to influence all three (party, ideological and ethnic) types of polarisation in varying but significant degrees.
Effectiveness of the Corrective Babbling Speech Treatment Program for Children with a History of Cleft Palate or Velopharyngeal Dysfunction

Objective To investigate the effectiveness of a phonetic-based, parent-administered treatment to reduce cleft-related speech errors. Design Immediate treatment (IT) versus delayed treatment (DT) comparison followed by analysis of gains over approximately 4 months and again after a longer period of treatment for participants in both groups. Participants Thirteen participants with a history of cleft palate or velopharyngeal dysfunction and speech disorder. Intervention After training, parents were instructed to conduct daily 10-minute sessions of phonetic drills with their children. Main Outcome Measures Group differences in percent consonants correct (PCC) were compared between those who did and those who did not receive the treatment. Pre- and posttreatment PCC comparisons were made after approximately 4 months of treatment and after termination of treatment. Results Participants receiving Corrective Babbling therapy showed significant gains in PCC in limited contexts after 4 months of therapy. However, gains were not significantly greater for the IT versus DT group. Participants who continued with the treatment for longer than 4 months showed the greatest gains in PCC and had significant improvements in all speech contexts assessed. Parents reported satisfaction with the program. Conclusions The results of this study indicate that this treatment shows promise for at least some children with a history of cleft palate and velopharyngeal dysfunction.
Disability in Everyday Life

The authors explored how persons with disabilities perceived the experience of disability in their everyday lives. The findings suggest that the current models in the literature do not address disability adequately. Instead, disability was described as a multifaceted, complex experience that is integrated into the lives of persons with disabilities. The degree to which integration was possible was influenced by three disability-related factors: (a) the fundamental effects of the disabling condition, (b) others’ perceptions of disability, and (c) the need for and use of resources. Important contextual conditions included the environment, time, and experience. Ultimately, it was the match between how these persons perceived themselves and what was important in their lives, and the influence of the three factors that determined how well they were able to integrate disability into their lives. The findings suggest the need for a conceptual model that reflects the personal experience of disability.
Fluvastatin Alters Platelet Aggregability in Patients With Hypercholesterolemia: Possible Improvement of Intraplatelet Redox Imbalance via HMG-CoA Reductase

Background—Hypercholesterolemia enhances platelet aggregability. Statins have beneficial effects on cardiovascular events. The purpose of this study is to investigate whether statins inhibit platelet aggregation and, if so, the mechanisms. Methods and Results—Twelve patients with hypercholesterolemia were prospectively randomized in a crossover design to receive either fluvastatin (20 mg/d) or colestimide (3000 mg/d) for 12 weeks. The subjects were switched to the opposite arm for additional 12 weeks. Before and after first and second treatments, experiments were performed. Eleven age-matched volunteers with normal lipid profiles served as controls. ADP-induced platelet aggregation, platelet-derive nitric oxide (PDNO) release, intraplatelet levels of GSH and GSSG, and intraplatelet nitrotyrosine production during platelet aggregation were measured. Fluvastatin and colestimide equally lowered total and low density lipoprotein cholesterol levels in hypercholesterolemia. Platelet aggregation was greater in hypercholesterolemia than in normocholesterolemia before treatment and was altered by fluvastatin. PDNO release, intraplatelet glutathione level, and GSH/GSSG ratio were lower in hypercholesterolemia than in normocholesterolemia before treatment and were increased by fluvastatin. Intraplatelet nitrotyrosine formation was greater in hypercholesterolemia than in normocholesterolemia, and decreased by fluvastatin. Colestimide did not have such effects. In vitro application of fluvastatin dose-dependently inhibited platelet aggregation. Furthermore, in vitro application of fluvastatin dose-dependently inhibited platelet nitrotyrosine expressions and the inhibitory effects by fluvastatin were reversed by preincubation with geranylgeranylpyrophosphate. Conclusions—Fluvastatin altered platelet aggregability in hypercholesterolemic patients in a cholesterol-lowering independent manner, which was partly mediated by the improvement of intraplatelet redox imbalance.
Assessing Dimensions of Competency to Stand Trial

Four decades of forensic research have left unanswered a fundamental issue regarding the best conceptualization of competency to stand trial vis-à-vis the Dusky standard. The current study investigated three competing models (discrete abilities, domains, and cognitive complexity) on combined data ( N = 411) from six forensic and correctional samples. Using the Evaluation of Competency to Stand Trial–Revised (ECST-R), items representative of the Dusky prongs were used to test the three models via maximum-likelihood confirmatory factor analyses (CFA). Of the three, only the discrete abilities model evidenced a good fit, indicating that competency to stand trial should consider separately each defendant’s factual understanding of the proceedings, rational understanding of the proceedings, and ability to consult with counsel. ECST-R competency scales, based on the current CFA, have excellent alphas (.83 to .89) and interrater reliabilities (.97 to .98).
The Dark Side of Wars for Talent and Layoffs: Evidence from Korean Firms †

In this study, we examined the effects of layoffs and wars for talent on firms’ performance. The simultaneous use of layoffs and “war-for-talent” practices has become part of the management strategy for adjusting workforce competencies. We suggest that war-for-talent practices decrease organizational performance when laying people off at the same time. Moreover, we argue that investment in employees’ skill development during the same period as layoffs and a war for talent can enhance organizational sustainability in increasing employee commitment, trust and organizational flexibility. Using a longitudinal survey conducted at over 653 Korean firms by a government-sponsored research institution, the results show that war-for-talent practices do not have a significant impact on firms’ performance. Moreover, our findings indicate a negative relationship between war-for-talent practices and financial performance when conducting layoffs and, as expected, a positive effect of the interaction between a war for talent and layoffs on turnover. Lastly, the results indicate a negative effect on organizational performance in firms pursuing a war for talent is mitigated when investments in employee development are continued during periods of layoffs.
Prevalence of eating disorders and minor psychiatric morbidity in Central Europe before the political changes in 1989: a cross-cultural study

SYNOPSIS The prevalence of culture-bound syndromes such as eating disorders in the countries of Central and Eastern Europe is unclear and comparative epidemiological studies are lacking. Before the political changes in 1989 we therefore investigated eating disorders, eating attitudes and psychological health in two Eastern European countries and in one Western democracy. A total of 1225 female and male medical students in Hungary, the German Democratic Republic (GDR) and Austria were surveyed. The instruments included the Eating Disorder Inventory and the GHQ. The prevalence of eating disorders was calculated on the basis of simulated DSM-III-R diagnosis. In females, bulimia nervosa prevalence rates of 0·6% (95% CI 0·02, 3·46), 1% (0·2, 2·95) and 0% (0, 2·07) were calculated for Austria, Hungary and the GDR, respectively. For subclinical bulimia nervosa, the rate for Hungary (3·8%; 1·95, 6·72) was twice as high as for Austria (1·9%; 0·39, 5·5) and the GDR (1·7%; 0·36, 4·88). Hungarian subjects indicated more psychiatric ‘caseness’ than their GDR or Austrian counterparts. We conclude that eating disorders represented at least as common a problem in Eastern as Western Europe before the changes in political organization. This may be due to an identification process with Western values. A further increase of eating disorders in these countries induced by the recent changes may be possible.