Miracle-dz/UniFAR-FTUs huggingface dataset:
Phase I/II study of FOLFIRI in Japanese patients with advanced colorectal cancer.

OBJECTIVE This phase I/II study determined the recommended dose of FOLFIRI (irinotecan, infusional 5-fluorouracil and leucovorin) for Japanese patients with advanced colorectal cancer, and evaluated safety at the recommended dose in patients without the UDP-glucuronosyltransferase 1A1*28 allele which caused reduced enzyme expression. METHODS The phase I part assessed the maximum tolerated dose of FOLFIRI to determine the recommended doses of irinotecan and infusional 5-fluorouracil. The doses were escalated from 150 to 180 mg/m(2) (irinotecan) and 2000 to 2400 mg/m(2) (5-fluorouracil). UDP-glucuronosyltransferase 1A1*6 and *28, and pharmacokinetics of irinotecan were observationally examined. In the phase II part, patients without the UDP-glucuronosyltransferase 1A1*28 allele received FOLFIRI at the recommended dose to evaluate safety. RESULTS Among 15 patients in the phase I part, dose-limiting toxicity (diarrhea) occurred in one patient who received 150 mg/m(2) irinotecan and 2400 mg/m(2) infusional 5-fluorouracil. The respective recommended doses were 180 and 2400 mg/m(2) for irinotecan and infusional 5-fluorouracil, without reaching the maximum tolerated dose. Twenty-five patients received FOLFIRI at the recommended doses. Grade 3 or 4 neutropenia occurred in 44%, and Grade 3 diarrhea in 4%. CONCLUSIONS This phase I/II study demonstrates that the recommended doses of irinotecan and infusional 5-fluorouracil in FOLFIRI for Japanese patients with advanced colorectal cancer who do not possess the UDP-glucuronosyltransferase 1A1*28 allele are 180 and 2400 mg/m(2), respectively. Toxicities occurring at the recommended doses are manageable in these patients.
High-Energy Proximal Femur Fractures in Geriatric Patients

Background: There is limited information in the literature on the outcomes and complications in elderly patients who sustain high-energy hip fractures. As the population ages, the incidence of high-energy geriatric hip fractures is expected to increase. The purpose of this study was to analyze the outcomes and complications in patients aged 65 years or older, who sustained a high-energy proximal femur fracture. Methods: Retrospective review of a prospective trauma database from January 2000 to April 2011 at a single US academic level-1 trauma center. Inclusion criteria consisted of all patients of age 65 years or older, who sustained a proximal femur fracture related to a high-energy trauma mechanism. Details concerning injury, acute treatment, and clinical course and outcome were obtained from medical records and radiographs. Results: We identified 509 proximal femur fractures in patients older than 65 years of age, of which 32 (6.3%) were related to a high-energy trauma mechanism. The mean age in the study group was 72.2 years (range 65-87), with a mean injury severity score of 20 points (range 9-57). Three patients died before discharge (9.4%), and 22 of 32 patients sustained at least one complication (68.8%). Blunt chest trauma represented the most frequently associated injury, and the main root cause of pulmonary complications. The patients' age and comorbidities did not significantly correlate with the rate of complications and the 1-year mortality. Conclusions: High-energy proximal femur fractures in elderly patients are not very common and are associated with a low in-hospital mortality rate of less than 10%, despite high rate of complications of nearly 70%. This selective cohort of patients requires a particular attention to respiratory management due to the high incidence of associated chest trauma.
The Determinants of Promotion to High Public Office in Germany: Partisan Loyalty, Political Craft, or Managerial Competencies?

The politicization of bureaucracy is a widespread strategy to increase the political control of ministerial departments in parliamentary democracies. It is, however, largely unknown why executive politicians promote some officials rather than others to high public office. Based on a unique dataset of all senior officials in German federal ministries and agencies that held office in the period 1997-2015, this article investigates whether partisan loyalty, political craft, and managerial competencies influence the chance of promotion to the highest civil service position in Germany (state secretary). We apply event history modelling to draw inferences on the relative importance of different selection criteria used by ministers when recruiting state secretaries from a candidate pool of senior officials. A key finding is that ministers consistently prefer politically loyal to non-loyal candidates. Although ministers also consider candidates’ political craft and selected managerial competencies, they are likely to trade-off partisan loyalty against those qualifications. The article contributes to the literature on politicization in the public sector by comparing potential and actual office holders and by including a broad set of selection criteria, moving beyond the literature’s dominating focus on partisan loyalty. The methodological approach developed in this article may well be transferred to other institutional contexts and used for comparative studies in this area.
The effect of light history on the aspartate-isolated fast-PIII responses of the albino rat retina.

PURPOSE To assess the effect of light-rearing history on the photon-capturing ability, amplitude, and kinetics of the fast-PIII response of the retina. METHODS Albino rats were raised on 12-hour light-12-hour dark cycles, with illumination at 3 lux or 200 lux, and killed at approximately 12 weeks. Retinal rhodopsin content was measured spectrophometrically. The morphology of the rod outer segments (ROS) and the thickness of the outer nuclear layer were determined histologically. Electroretinograms of isolated retinas to 3-microsecond flashes were recorded. The kinetics of fast PIII responses were assessed with a model of the phototransduction cascade. RESULTS Total rhodopsin of 200 lux animals was reduced to 60% that of 3 lux animals: 2.3 +/- 0.2 versus 1.4 +/- 0.1 nmol/eye (mean +/- SD). Length of ROS of 200 lux animals was reduced to 68% of the length of that of 3 lux animals: 20.1 +/- 1.2 versus 13.7 +/- 0.5 microns. The saturated amplitude of fast PIII of 200 lux animals was reduced to 56% that of the 3 lux group: 134 +/- 27 versus 239 +/- 37 microV (T = 22 degrees C). Fast PIII responses of both groups are well described by the kinetic model before slow PIII intrusion (up to 100 ms). Estimated kinetic parameters of the transduction cascade did not differ reliably between the two groups. CONCLUSIONS Diminished saturated amplitude of fast PIII in 200 lux animals is accounted for by the hypothesis that fast PIII is directly proportional to the rod photocurrent and by the finding that the ROS of 200 lux animals are short compared to those of 3 lux animals. Similarity in estimated kinetic parameters of phototransduction suggests that the rods of the two groups differ little in the biochemistry underlying the activation phase of phototransduction.
Agents targeting c-Jun N-terminal kinase pathway as potential neuroprotectants

c-Jun N-terminal kinase (JNK) plays an integral role in neuronal death in multiple cell lines following a wide variety of stimuli and in a number of physiological functions that may be involved in human disease, including CNS diseases. In the past decades, many researchers in this field have found and reinforced the concept that prolonged activation of JNK signalling can induce neuronal cell death by both a transcriptional induction of death-promoting genes and modulation of the mitochondrial apoptosis pathways. Data are emerging to extend the understanding of the JNK signalling and confirm the possibility that targeting JNK signalling may offer an effective therapy for pathological conditions in the near future. This review will focus on the pro-apoptotic role of JNK signalling and updated pharmacological inhibitors of this pathway.
The Determinants of Emerging Financial Markets Development: A Case Study of the Dar es Salaam Stock Exchange, Tanzania

The stock market plays a vital role in financial intermediation in developed and developing economies (Laichena & Obwogi, 2015). That is because stock markets provide a platform for surplus resources to be transferred to deficit areas. Developing countries lack efficient stock markets like those of the developed countries (Coleman & Tetty, 2008). Therefore, the study sought to investigate the determinants of emerging financial market development using the Dar es Salaam Stock Exchange, Tanzania as a case study. The study had the following specific objectives: to analyze the extent by which market liquidity determines development of emerging financial markets, to establish how inflation rates decides the development of emerging financial markets, to explore how market volatility concludes the development of emerging financial markets and to establish how economic growth determines the development of emerging financial markets. Relevant empirical and theoretical literature was reviewed to inform the objectives of the study and to also form a ground for discussion of results. The study employed a multivariate times series econometric design. The target population of the study included the DSE financial statement data and statistical data from the National Bureau of Statistics, Tanzania. The study used secondary data spanning the period between 2007 and 2016. The data used for the analysis were the monthly figures obtained from the Dar es Salaam Stock Exchange and the National Bureau of Statistics of Tanzania. Diagnostic and model specification tests were done on the data using E-Views version 9. Data was treated for the problem of time series data. To compute forecasts from models with cointegration restrictions, the model is transformed into the VAR levels representation (Bruggemann, 2004). Thus the study used the unrestricted vector autoregressive (VAR) model to do a regression of the dependent variables on the independent variables. The study results were interpreted based on the VAR output. The study concluded that stock market volatility, stock market liquidity and economic growth had a positive and significant long-run relationship with financial market development. Whereas, inflation rates had a negative and insignificant relationship with financial market development. The study recommended that Tanzania relooks at and optimizes its expansionary monetary policy. Policymakers should follow or implement policies which raise macroeconomic stability considering the interaction between economic growth and stock market development. Keywords: stock exchange, emerging market, market capitalization
Association of metabolic syndrome with smoking and alcohol intake in Japanese men.

INTRODUCTION There have been conflicting findings on whether metabolic syndrome (MetS) is associated with smoking and alcohol intake. This study investigated the association of MetS with smoking and alcohol intake. METHODS MetS was defined according to the International Diabetes Federation criteria, and smoking and alcohol intake were evaluated for 1,215 Japanese male workers using a questionnaire. The association of MetS with smoking and alcohol intake was assessed using logistic regression after adjusting for potential confounders. Proportional analyses for the prevalence of MetS among smoking and alcohol intake were performed as well. RESULTS Among the subjects, 148 (12%) were diagnosed with MetS, 485 (40%) were smokers, and 954 (79%) were regular alcohol users. The prevalence of MetS was the highest (19%) in smokers who did not drink, followed by smokers who also drank (13%), nonsmokers who drank (12%), and those who neither smoked nor drank (7%). Smoking itself was positively related to MetS (odds ratio [OR] = 1.4; 95% CI = 1.1-2.1) and MetS components, including larger waist circumference (OR = 1.5; 95% CI = 1.2-1.9), elevated triglyceride (OR = 1.9; 95% CI = 1.4-2.4), and reduced high-density lipoprotein cholesterol (OR = 1.7; 95% CI = 1.1-2.7). Alcohol intake was not significantly related to MetS; it was positively correlated only to higher fasting plasma glucose (OR = 1.7; 95% CI = 1.1-2.6). DISCUSSION These results suggest that cigarette smoking is an independent risk factor for MetS, but the risk does not seem to be exaggerated by alcohol intake.
Evaluation Following Staggered Implementation of the “Rethinking Critical Care” ICU Care Bundle in a Multicenter Community Setting*

Objectives:To evaluate process metrics and outcomes after implementation of the “Rethinking Critical Care” ICU care bundle in a community setting. Design:Retrospective interrupted time-series analysis. Setting:Three hospitals in the Kaiser Permanente Northern California integrated healthcare delivery system. Patients:ICU patients admitted between January 1, 2009, and August 30, 2013. Interventions:Implementation of the Rethinking Critical Care ICU care bundle which is designed to reduce potentially preventable complications by focusing on the management of delirium, sedation, mechanical ventilation, mobility, ambulation, and coordinated care. Rethinking Critical Care implementation occurred in a staggered fashion between October 2011 and November 2012. Measurements and Main Results:We measured implementation metrics based on electronic medical record data and evaluated the impact of implementation on mortality with multivariable regression models for 24,886 first ICU episodes in 19,872 patients. After implementation, some process metrics (e.g., ventilation start and stop times) were achieved at high rates, whereas others (e.g., ambulation distance), available late in the study period, showed steep increases in compliance. Unadjusted mortality decreased from 12.3% to 10.9% (p < 0.01) before and after implementation, respectively. The adjusted odds ratio for hospital mortality after implementation was 0.85 (95% CI, 0.73–0.99) and for 30-day mortality was 0.88 (95% CI, 0.80–0.97) compared with before implementation. However, the mortality rate trends were not significantly different before and after Rethinking Critical Care implementation. The mean duration of mechanical ventilation and hospital stay also did not demonstrate incrementally greater declines after implementation. Conclusions:Rethinking Critical Care implementation was associated with changes in practice and a 12–15% reduction in the odds of short-term mortality. However, these findings may represent an evaluation of changes in practices and outcomes still in the midimplementation phase and cannot be directly attributed to the elements of bundle implementation.
Bulimia Nervosa: Family Size, Sibling Sex and Birth Order

Family size, sex of siblings and birth order were examined in 225 bulimic patients of normal weight, all stemming from the same circumscribed catchment area. Although bulimia can occur in any size family, all-female sibships were significantly over-represented. In small families at least, the bulimic patient was highly likely to be the only or eldest daughter. In small sibships, a bulimic who was first-born was significantly more likely to have a younger sister; if second-born she was more likely to have an elder brother. Despite the very large sample size, no final conclusion can be made on birth order.
Double Trouble: A review of the relationship between UK poverty and economic inequality

The link between inequality and poverty has been highlighted by a number of international organisations, which have outlined a series of policy recommendations supporting the view that high levels of inequality need to be tackled even if the central objective is to reduce poverty. This report makes clear there is a positive correlation between income inequality and relative income poverty in the UK. The strength of this connection depends on which measure of inequality is used and this report makes no claim about causation – but the central conclusion is clear. We can no longer treat poverty and economic inequality as separate problems which can be tackled in isolation. They are instead closely linked and must be tackled together.
Distortion by Ophthalmic Lenses Calculated at the Farpoint Sphere

ABSTRACT Distortion by ophthalmic lenses has generally been calculated with respect to an ideal flat image surface. This results in improper distortion values as the ideal image surface for the mobile eye is the farpoint sphere. Results of distortion calculations for lenses ranging from +20 to −24.65 D are given for point focal lenses (corrected for oblique astigmatism), Percival lenses (designed to place the circle of least confusion on the farpoint sphere), minimum astigmatism and minimum distortion lens forms. Distortion of point focal Ostwalt lenses of powers +6.60 to −24.65 D range from 4.45 to −28.31% when computed at the flat image surface. Referred to the farpoint sphere the corresponding distortion values are +0.85 to −13.54%. Similarly, the distortion of the minimum astigmatic forms of lenses ranging in power from +20 to +7 D are +27.31 to 4.64% at the flat image surface but decrease to +16.38 to 0.84%, respectively, at the farpoint sphere. If the rotations of the unaided ametropic eye that are required to fixate two points in the field are compared with the necessary rotations with a spectacle correction (+20 to −24 D), it is found that the corrected eye rotation errors at the flat image surface range from 14.87 to −4.53%, but drop to +0.87 to −1.88% when referred to the farpoint sphere. It is concluded that distortion at the farpoint sphere is a more valid measure of distortion for the mobile eye than the classical measurement of distortion. This has implications for the study of space perception through lenses.
Determinants of Credit Constraints: Evidence from Sindh, Pakistan

ABSTRACT This article investigates the determinants of credit constraints: evidence from Sindh, Pakistan. Cross-sectional farm-level data is collected during November and December 2016. A sample of 180 farm households is selected for interviews by using a multistage, random sampling technique. This study employed a probit regression model, frequency counts, and percentages to analyze the data. Access to formal agricultural credit is relatively low in Sindh province of Pakistan, the findings of the study show that the major constraints comprise distance to the formal credit sources, lending procedure, time lag, and interest rate whereas land ownership has a negative association and reduces the constraints to access formal credit. The findings of this study also show that for efficient allocation of resources, institutional sources of credit preferred to disburse agricultural credits toward educated and young age farmers as they are more inclined to adopt new farm technology for better farm production.
Retrospective Diagnosis of Parkinsonian Syndromes Using Whole-Brain Atrophy Rates

Objective: The absence of markers for ante-mortem diagnosis of idiopathic Parkinson's disease (IPD), multiple system atrophy (MSA), and progressive supranuclear palsy (PSP) results in these disorders being commonly mistaken for each other, particularly in the initial stages. We aimed to investigate annualized whole-brain atrophy rates (a-WBAR) in these disorders to aid in the diagnosis between IPD vs. PSP and MSA. Methods: Ten healthy controls, 20 IPD, 39 PSP, and 41 MSA patients were studied using Structural Imaging Evaluation with Normalization of Atrophy (SIENA). SIENA is an MRI-based algorithm that quantifies brain tissue volume and does not require radiotracers. SIENA has been shown to have a low estimation error for atrophy rate over the whole brain (0.5%). Results: In controls, the a-WBAR was 0.37% ± 0.28 (CI 95% 0.17–0.57), while in IPD a-WBAR was 0.54% ± 0.38 (CI 95% 0.32–0.68). The IPD patients did not differ from the controls. In PSP, the a-WBAR was 1.93% ± 1.1 (CI 95% 1.5–2.2). In MSA a-WBAR was 1.65% ± 0.9 (CI 95%1.37–1.93). MSA did not differ from PSP. The a-WBAR in PSP and MSA were significantly higher than in IPD (p < 0.001). a-WBAR 0.6% differentiated patients with IPD from those with PSA and MSA with 91% sensitivity and 80% specificity. Conclusions: a-WBAR within the normal range is unlikely to be observed in PSP or MSA. a-WBAR may add a potential retrospective application to improve the diagnostic accuracy of MSA and PSP vs. IPD during the first year of clinical assessment.
Contribution to income inequality by income source: A comparison across ethnic groups in Vietnam

This study explores the dynamics of income and income inequality in Vietnam from 2004 to 2014. Two main sub-population groups are investigated: the ethnic majority, known as the Kinh people, and the minority group, which includes 53 minor ethnicities in Vietnam. The findings show that income gap among ethnic groups has increased over the last decade. The Gini index decomposition indicates that wages and nonfarm income are the two main determinants of income inequality. Cultivation and agricultural side-line incomes were relatively evenly distributed, despite their recent smaller equalizing effect. Both sub-population groups have experienced a decreasing contribution of the agricultural sector to overall household income. The changes in income inequality in Vietnam by income sources reflect the economic structure change of the economy from the agricultural reliance to non-agricultural economic activities.
Promising biomarkers for predicting the outcomes of patients with KRAS wild‐type metastatic colorectal cancer treated with anti‐epidermal growth factor receptor monoclonal antibodies: A systematic review with meta‐analysis

KRAS mutations have been established as a major predictive biomarker for resistance to the treatment of metastatic colorectal cancer (mCRC) with anti‐epidermal growth factor receptor monoclonal antibodies (anti‐EGFR MoAbs). However, many patients with KRAS wild‐type tumors still do not respond to the treatment. We conducted a systematic review with meta‐analysis to assess whether BRAF mutations, PIK3CA mutations and PTEN loss can predict the outcomes of patients with KRAS wild‐type mCRC treated with anti‐EGFR MoAbs. Studies that explored the association of one or more of the three biomarkers with progression‐free survival (PFS), overall survival (OS) and/or objective response rate (ORR) were identified through August 2012. Summary hazard ratios (HRs) and rate differences (RDs) and corresponding 95% confidence intervals (CIs) were calculated by using the random‐effects model. BRAF mutations, PIK3CA exon 20 mutations and PTEN loss were all associated with shorter PFS (HR = 2.59, 95% CI 1.67–4.03; HR = 2.52, 95% CI 1.33–4.78 and HR = 1.75, 95% CI 1.19–2.56, respectively), shorter OS (HR = 2.74, 95% CI 1.79–4.19; HR = 3.29, 95% CI 1.60–6.75 and HR = 1.85, 95% CI 1.30–2.64, respectively) and lower ORR (RD = −36%, 95% CI −44 to −28%; RD = −38%, 95% CI −51 to −24% and RD = −41%, 95% CI −68 to −14%, respectively). PIK3CA exon 9 mutations were associated with none of the outcomes. Studies with relevant data consistently demonstrated a stronger predictive power of combined multiple biomarkers as compared to one alteration alone. These results suggest that BRAF mutations, PIK3CA exon 20 mutations and PTEN loss are predictive of better outcomes in KRAS wild‐type mCRC treated with anti‐EGFR MoAbs. However, the quality of included studies varied, and some of the meta‐analyses were limited by significant between‐study heterogeneity. In the future, well‐designed large randomized controlled trials conducted in KRAS wild‐type mCRC patients with subgroup analysis according to BRAF, PIK3CA exon 20 and PTEN status are essential to fully assess the clinical relevance of these biomarkers.