Miracle-dz/UniFAR-FTUs huggingface dataset:
Updated analysis of the phase III, double-blind, randomized, multinational study of radium-223 chloride in castration-resistant prostate cancer (CRPC) patients with bone metastases (ALSYMPCA).

LBA4512 Background: Radium-223 chloride (Ra-223), a targeted alpha-emitter, targets bone metastases (mets) with high-energy alpha-particles of short range (<100 µm). ALSYMPCA, a phase III double-blind, randomized, multinational study, compared Ra-223 plus best standard of care (BSC) vs placebo plus BSC in CRPC patients (pts) with bone mets. In a planned interim analysis (n = 809), based on 314 events, Ra-223 significantly improved overall survival (OS) vs placebo (median 14.0 mo vs 11.2 mo, respectively; HR = .695; 95% CI, .552-.875; 2-sided p = .00185). Secondary endpoints were met and Ra-223 safety was favorable. An updated analysis was conducted prior to the crossover to further assess the effect of Ra-223 on the primary endpoint (OS), secondary endpoints including skeletal-related events (SREs), and safety. METHODS Eligible pts had confirmed symptomatic CRPC with ≥ 2 bone mets; no known visceral mets; and were post-docetaxel, unfit for docetaxel, or had declined docetaxel. Pts were randomized 2:1 to receive 6 injections of Ra-223 (50 kBq/kg IV) q4wks or matching placebo. An updated descriptive analysis of OS, based on 528 events, was performed including data from all randomized pts prior to implementing crossover to Ra-223 for placebo pts. RESULTS 921 pts (Ra-223, n = 614; placebo, n = 307) were randomized from 6/2008-2/2011. Ra‑223 significantly improved OS vs placebo (median 14.9 mo vs 11.3 mo, respectively; HR = .695; 95% CI, .581-.832; p = 0.00007), and time to first SRE was significantly prolonged (median 15.6 mo vs 9.8 mo, respectively; HR = 0.658; 95% CI, 0.522-0.830; p = 0.00037). Safety and tolerability of Ra-223 remained favorable, with low myelosuppression (e.g., gr 3/4 neutropenia in 2.2% and 0.7% and gr 3/4 thrombocytopenia in 6.3% and 2% of the Ra-223 and placebo groups, respectively). CONCLUSIONS On updated analysis, the median OS benefit for Ra-223 increased from 2.8 to 3.6 months, with a hazard ratio of 0.695 (i.e., 30.5% reduction in risk of death). Ra-223 is an effective therapy that improves OS and time to first SRE with a highly favorable safety profile, and may provide a new standard of care for CRPC pts with bone mets.
Chapter 7 Patuki and Croisilles melanges in South Island, New Zealand: genesis related to Permian subduction–accretion processes

Abstract The late Early Permian (c. 278–270 Ma) supra-subduction zone (SSZ) Dun Mountain ophiolite is bordered to the east by the Pataki Melange and to the NE by the Croisilles Melange. In the south, the ophiolite passes into a dismembered incipient oceanic arc (Otama Complex). The above units represent an oceanic forearc generated above a west-dipping subduction zone. Terrigenous sediment reached the subduction trench after the Mid-Permian(? ) docking of the oceanic forearc with the long-lived SE Gondwana active continental margin. Mixed terrigenous–volcaniclastic turbidites accumulated in the trench prior to and during melange accretion. Fragments of the overriding oceanic forearc (and incipient arc, locally) detached and mixed to form melange and broken formation. Despite some individual features (e.g. of the basalt chemistry), the Patuki and Croisilles melanges are interpreted as originally representing a single Permian trench–accretionary complex. The more distal (easterly) part was sliced into the adjacent accretionary complex of the Caples Terrane to form the Croisilles Melange (and equivalent Greenstone Melange) probably after the Triassic. The South Island melanges exemplify accretionary processes in which igneous and sedimentary rocks were detached from the overriding plate by subduction–erosion, together with accretion, including seamount material from the subducting oceanic plate, with implications for melanges elsewhere.
Antimicrobial resistance pattern among aerobic gram-negative bacilli of lower respiratory tract specimens of intensive care unit patients in a neurocentre.

BACKGROUND Analysis of the tracheal and bronchial isolates from the lower respiratory tract specimens of the intensive care unit (ICU)-admitted patients, was carried out for the year 2002 with a perspective of looking at the antibiotic resistance pattern. METHODS Lower respiratory tract secretions (tracheal or bronchoscopic aspirates) of 370 patients were cultured, identified and antimicrobial susceptibility performed by standard methods. RESULTS Out of samples obtained from 370 patients, 274 (74%) were culture positive. A total of 489 bacterial isolates were recovered from 270 patients; 451 were gram-negative bacilli (GNB) and 38 were Staphylococcus aureus. In four of the patients, Candida spp was isolated. The common GNB isolates were non-fermentative gram-negative bacilli (NFGNB, 31.9%), followed by Pseudomonas aeruginosa (21.5%) and Klebsiella spp (19%). Elderly (24.8%) and adults (19.2%) showed increased rate of GNB isolation. In both tracheal and bronchial GNB isolates, the highest mean resistance was to cefazolin (98.8%) and ampicillin (97.6%) while the lowest mean resistance was to amikacin (48.5%). Isolation of two organisms per specimen (41.4%) was commonly seen. Multidrug resistance to the tested antimicrobials was more frequent in NFGNB (6.6%) and Pseudomonas aeruginosa (5%). There were no remarkable differences in the overall mean drug resistance among tracheal and bronchial GNB isolates. CONCLUSIONS Isolation practices, antibiotic policies, effective surveillance, maintenance of epidemiological trends of infections and, rapid molecular diagnosis are the need of hour in improved and speedy management of lung infections with resistant organisms.
Reduced Levels of Chloroplast FtsH Protein in Tobacco Mosaic Virus–Infected Tobacco Leaves Accelerate the Hypersensitive Reaction

In tobacco cultivars resistant to tobacco mosaic virus (TMV), infection results in the death of the infected cells accompanying the formation of necrotic lesions. To identify the genes involved in this hypersensitive reaction, we isolated the cDNA of tobacco DS9, the transcript of which decreases before the appearance of necrotic lesions. The DS9 gene encodes a chloroplastic homolog of bacterial FtsH protein, which serves to maintain quality control of some cytoplasmic and membrane proteins. A large quantity of DS9 protein was found in healthy leaves, whereas the quantity of DS9 protein in infected leaves decreased before the lesions appeared. In transgenic tobacco plants containing less and more DS9 protein than wild-type plants, the necrotic lesions induced by TMV were smaller and larger, respectively, than those on wild-type plants. These results suggest that a decrease in the level of DS9 protein in TMV-infected cells, resulting in a subsequent loss of function of the chloroplasts, accelerates the hypersensitive reaction.
Are Grocery Shoppers of Households with Weight-Concerned Members Willing to Pay More for Nutrtional Information on Food?

This study used eye-tracking technology and an experimental auction to unveil shoppersâ€™ visual usage of nutrition information and willingness to pay (WTP) for food. Particular attention was given to primary grocery shoppers of households having weight-concerned members (shoppers included). The results showed that shoppers of household with weight-concerned members were more attentive to nutritional label information. Furthermore, their WTP for roasted peanuts decreased as their visual attention to the fat and sugar content increased. In addition, they were willing to pay more for salad mix compared to other shoppers. Health claims did not have an effect on shoppersâ€™ WTP.
Efficacy of a 6-month versus 9-month intermittent treatment regimen in HIV-infected patients with tuberculosis: a randomized clinical trial.

RATIONALE The outcome of fully intermittent thrice-weekly antituberculosis treatment of various durations in HIV-associated tuberculosis is unclear. OBJECTIVES To compare the efficacy of an intermittent 6-month regimen (Reg6M: 2EHRZ(3)/4HR(3) [ethambutol, 1,200 mg; isoniazid, 600 mg; rifampicin, 450 or 600 mg depending on body weight <60 or > or =60 kg; and pyrazinamide, 1,500 mg for 2 mo; followed by 4 mo of isoniazid and rifampicin at the same doses]) versus a 9-month regimen (Reg9M: 2EHRZ(3)/7HR(3)) in HIV/tuberculosis (TB). METHODS HIV-infected patients with newly diagnosed pulmonary or extrapulmonary TB were randomly assigned to Reg6M (n = 167) or Reg9M (n = 160) and monitored by determination of clinical, immunological, and bacteriological parameters for 36 months. Primary outcomes included favorable responses at the end of treatment and recurrences during follow-up, whereas the secondary outcome was death. Intent-to-treat and on-treatment analyses were performed. All patients were antiretroviral treatment-naive during treatment. MEASUREMENTS AND MAIN RESULTS Of the patients, 70% had culture-positive pulmonary TB; the median viral load was 155,000 copies/ml and the CD4(+) cell count was 160 cells/mm(3). Favorable response to antituberculosis treatment was similar by intent to treat (Reg6M, 83% and Reg9M, 76%; P = not significant). Bacteriological recurrences occurred significantly more often in Reg6M than in Reg9M (15 vs. 7%; P < 0.05) although overall recurrences were not significantly different (Reg6M, 19% vs. Reg9M, 13%). By 36 months, 36% of patients undergoing Reg6M and 35% undergoing Reg9M had died, with no significant difference between regimens. All 19 patients who failed treatment developed acquired rifamycin resistance (ARR), the main risk factor being baseline isoniazid resistance. CONCLUSIONS Among antiretroviral treatment-naive HIV-infected patients with TB, a 9-month regimen resulted in a similar outcome at the end of treatment but a significantly lower bacteriological recurrence rate compared with a 6-month thrice-weekly regimen. ARR was high with these intermittent regimens and neither mortality nor ARR was altered by lengthening TB treatment. Clinical Trials Registry Information: ID# NCT00376012 registered at www.clinicaltrials. gov.
Concomitant use of cigarettes and smokeless tobacco: prevalence, correlates, and predictors of tobacco cessation.

BACKGROUND This study examined the characteristics, tobacco use patterns over time, and predictors of tobacco cessation among concomitant users of cigarettes and smokeless tobacco. METHODS Participants were employed adults residing in the southeastern United States who participated in the Working Well cancer prevention trial. Participants were assessed at baseline and followed-up 4 years later. RESULTS AND CONCLUSIONS The study yielded several key findings: (a) the prevalence of concomitant smoking and smokeless tobacco use was high among males and nonexistent among females, (b) the characteristics of concomitant users were relatively distinct from those of both smokers and smokeless tobacco users, (c) concomitant users exhibited substantial variability in their tobacco use patterns and were less likely to stop using tobacco than were smokers or smokeless tobacco users, (d) indicators of nicotine dependence predicted tobacco cessation for both smokers and smokeless tobacco users, but were largely unrelated to tobacco cessation among concomitant users, and (e) demographics, environmental variables, and measures derived from the transtheoretical model were not consistent predictors of tobacco cessation after controlling for nicotine dependence.
Use of the live attenuated Japanese Encephalitis vaccine SA 14–14–2 in children: A review of safety and tolerability studies

ABSTRACT Japanese encephalitis (JE) is the leading cause of viral neurological disease and disability in Asia. Some 50–80% of children with clinical JE die or have long-term neurologic sequelae. Since there is no cure, human vaccination is the only effective long-term control measure, and the World Health Organization recommends that at-risk populations receive a safe and effective vaccine. Four different types of JE vaccines are currently available: inactivated mouse brain-derived vaccines, inactivated Vero cell vaccines, live attenuated SA 14–14–2 vaccines and a live recombinant (chimeric) vaccine. With the rapidly increasing demand for and availability and use of JE vaccines, countries face an important decision in the selection of a JE vaccine. This article provides a comprehensive review of the available safety literature for the live attenuated SA 14–14–2 JE vaccine (LAJEV), the most widely used new generation JE vaccine. With well-established effectiveness data, a single dose of LAJEV protects against clinical JE disease for at least 5 years, providing a long duration of protection compared with inactivated mouse brain-derived vaccines. Since 1988, about 700 million doses of the LAJEV have been distributed globally. Our review found that LAJEV is well tolerated across a wide age range and can safely be given to children as young as 8 months of age. While serious adverse events attributable to LAJEV have been reported, independent experts have not found sufficient evidence for causality based on the available data.
HPR1, a novel yeast gene that prevents intrachromosomal excision recombination, shows carboxy-terminal homology to the Saccharomyces cerevisiae TOP1 gene

The HPR1 gene has been cloned by complementation of the hyperrecombination phenotype of hpr1-1 strains by using a color assay system. HPR1 is a gene that is in single copy on chromosome IV of Saccharomyces cerevisiae, closely linked to ARO1, and it codes for a putative protein of 752 amino acids (molecular mass, 88 kilodaltons). Computer searches revealed homology (48.8% conserved homology; 24.8% identity) with the S. cerevisiae TOP1 gene in an alpha-helical stretch of 129 amino acids near the carboxy-terminal region of both proteins. The ethyl methanesulfonate-induced hpr1-1 mutation is a single-base change that produces a stop codon at amino acid 559 coding for a protein that lacks the carboxy-terminal TOP1 homologous region. Haploid strains carrying deletions of the HPR1 gene show a slightly reduced mitotic growth rate and extremely high rates of intrachromosomal excision recombination (frequency, 10 to 15%) but have a undetectable effect on rDNA recombination. Double-null mutants hpr1 top1 grow very poorly. We conclude that Hpr1 is a novel eucaryotic protein, mutation of which causes an increase in mitotic intrachromosomal excision recombination, and that it may be functionally related to an activity of the topoisomerase I protein.
Cellular physiology of the turtle visual cortex: synaptic properties and intrinsic circuitry

We have examined the synaptic physiology of the isolated dorsal cortex of the turtle, Pseudemys scripta elegans. Electrical stimulation of afferent pathways elicited distinct, stereotyped responses in pyramidal and stellate neurons. Single shocks evoked a long-lasting barrage of excitatory postsynaptic potentials (EPSPs) in stellate cells, and led to a burst of several action potentials. Under the same circumstances, pyramidal cells displayed a small amount of short-latency excitation, but this was accompanied by a profound and prolonged set of inhibitory post-synaptic potentials (IPSPs). Synaptic excitation of the distal dendrites of pyramidal cells could evoke dendritic action potentials that were visible at the soma as small all-or-none spikes rising from the hyperpolarized level of the IPSP. There appeared to be two mechanistically different types of IPSPs in pyramidal cells. The first occurred at short latency, could produce a very large conductance increase, reversed polarity at -71 mV, and was chloride-dependent. The second was generally smaller and more protracted, had a relatively negative reversal potential of -85 to -95 mV, and was insensitive to chloride injection. Focal application of small doses of the putative inhibitory neurotransmitter gamma-aminobutyric acid (GABA) onto the somata of pyramidal cells caused a conductance increase and hyperpolarization. This response had features in common with the short- latency IPSP, including an identical reversal potential. Application of large doses of GABA to the somata of pyramidal cells or smaller doses to their dendrites elicited multiphasic or purely depolarizing responses that were at least partly due to time- or space-dependent shifts of the equilibrium potential of the response. Bicuculline methiodide, a potent GABA antagonist, depressed both the responses to GABA and the short-latency IPSP, but not the long-latency IPSP; synchronized epileptiform burst discharges also resulted. These findings, together with responses to locally applied electric shocks and the excitatory amino acid glutamate, suggested that inhibition of pyramidal cells was generated intrinsically by stellate cells, and that the cortical circuit provides pathways for both feedforward and feedback GABAergic inhibition. The data also suggest that pyramidal cells are mutually excitatory. These features are similar to the basic intrinsic circuitry in the telencephalic cortices of mammals.
Are there laws of motion of capitalism

This article takes seriously the conflict of paradigms between a market economy approach and a capitalism approach. The first has recurrently shown its inability to explain the major stylized facts of the last two decades. The second now receives more attention as a possible alternative but the field has been so underexplored by so few people that the task is somehow promethean. Is it possible to explicitly state laws of motion of capitalism? Previous failed attempts justify some scepticism. A review of the multiplicity of meanings and conceptualizations of ‘economic laws’ suggests first that the existence of general quantitative regularities, which economists are fond of, is quite unlikely. Second, it is possible to identify explicit partial and temporary regularities that are indexed upon a given institutional configuration of capitalism. Third, mobilizing the results of past historical analyses and building upon the contributions of some key economists and social scientists—Marx, Polanyi, Schumpeter, Kaldor, Wallerstein and Kindleberger—the article proposes seven conjectures about possible ‘laws of motion of capitalism’.
Dynamic Depositor Discipline: Evidence Based on East Asian Banks

This study confirms the endogenous relationship between the price and quantity of deposits in the depositor discipline model. Dynamic panel data analysis is carried out to account for the lagged dependency of the deposits growth variable and endogeneity of the price mechanism in the depositor discipline model. The results show that depositors in East Asia do not demand a higher price for deposits. Analysis by subdividing the sample of banks into healthy and weak banks shows that the relationship between price and quantity is not non-linear. Healthy banks are not able to attract more deposits by raising price. Depositors do not discipline weak banks by demanding a higher return. Lack of responsiveness by depositors to price signals may be attributable largely to the outflow of deposits that happened during the crisis period and regulations on interest rates. JEL Classification: G21, G28, N25
Evaluating Patterns of Income Growth When Status Matters: A Robust Approach

This paper addresses the problem of ranking growth episodes from a microeconomic perspective. While most of the existing criteria, framed in the pro-poor growth tradition, are either based on anonymous individuals or use to identify them on the base of their status in the initial period, this paper proposes new criteria to evaluate growth, which are robust to the choice of the reference period used to identify individuals. Suitable dominance conditions that can be used to rank alternative growth processes are derived by means of an axiomatic approach. Moreover, the theoretical results are used to rank the different growth episodes that took place in the last decade in Australia, Germany, Korea, Switzerland, and US.
A synthetic inhibitor of p53 protects neurons against death induced by ischemic and excitotoxic insults, and amyloid β‐peptide

The tumor suppressor protein p53 is essential for neuronal death in several experimental settings and may participate in human neurodegenerative disorders. Based upon recent studies characterizing chemical inhibitors of p53 in preclinical studies in the cancer therapy field, we synthesized the compound pifithrin‐α and evaluated its potential neuroprotective properties in experimental models relevant to the pathogenesis of stroke and neurodegenerative disorders. Pifithrin‐α protected neurons against apoptosis induced by DNA‐damaging agents, amyloid β‐peptide and glutamate. Protection by pifithrin‐α was correlated with decreased p53 DNA‐binding activity, decreased expression of the p53 target gene Bax and suppression of mitochondrial dysfunction and caspase activation. Mice given pifithrin‐α exhibited increased resistance of cortical and striatal neurons to focal ischemic injury and of hippocampal neurons to excitotoxic damage. These preclinical studies demonstrate the efficacy of a p53 inhibitor in models of stroke and neurodegenerative disorders, and suggest that drugs that inhibit p53 may reduce the extent of brain damage in related human neurodegenerative conditions.
Effects of cadmium on the control and internal regulation of oxidative phosphorylation in potato tuber mitochondria.

The effect of cadmium on the distribution of control over oxidative phosphorylation in potato tuber mitochondria was quantified by measuring control coefficients using top-down metabolic control analysis. Oxidative phosphorylation was divided into three subsystems, namely substrate oxidation, the phosphorylation reactions and the proton leak. The control exerted by each of these subsystems over the system fluxes, the value of the protonmotive force and the effective P/O ratio was quantified in the presence of different concentrations of free cadmium (up to 21 microM). Cadmium is known to stimulate the proton leak and inhibit the substrate oxidation reactions, but it had little effect on the distribution of control over the system variables except to shift the pattern to lower rates. Control exerted by particular subsystems appeared to change or to stay the same as cadmium was varied, depending on whether the control coefficients were presented as a function of respiration rate or protonmotive force. The regulatory strength of protonmotive force on the system variables was also calculated, as partial internal response coefficients. These coefficients changed with ATP turnover rate and with cadmium concentration, showing how the internal regulation of oxidative phosphorylation shifts under different conditions. The values of control coefficients and partial internal response coefficients show where control lies and how intermediates regulate the system variables under different conditions of ATP demand and external effector (i.e. cadmium) concentration. However, they are not useful for identifying the sites of action of external effectors, for which elasticity and regulation analysis must be used.
A rapid sample preparation method for PCR detection of food pathogens based on buoyant density centrifugation

The use of buoyant density centrifugation (BDC) to prepare samples for PCR analysis of food pathogens is described. Blue cheese and milk homogenates were inoculated with Shigella flexneri and layered on top of Percoll® media. After BDC, the food homogenates remained in the upper part of the centrifuge tube, separated from the bacteria, which retained viability and were concentrated below the lighter Percoll® layer. PCR inhibitors stayed in the homogenate and PCR analyses of treated samples consistently detected 104 cfu g−1 of blue cheese and 500 cfu ml−1 of milk, respectively. Differences in the density of live and killed Sh. flexneri and Yersinia enterocolitica were detected by BDC but were dependent on the mechanism of killing.