Miracle-dz/UniFAR-FTUs huggingface dataset:
Antiviral therapy and hepatitis B virus-related hepatocellular carcinoma recurrence.

To the Editor: Although using antiviral therapy to suppress hepatitis B virus (HBV) replication after curative resection of hepatocellular carcinoma (HCC) is thought to potentially reduce the rate of HCC recurrence, studies regarding the efficacy of nucleoside analogues in this clinical setting are limited and thus controversial. In the study by Dr Wu and colleagues, the authors used the Taiwan National Health Insurance Research Database for analysis and reported that the use of a nucleoside analogue was associated with a lower risk of HCC recurrence among patients with HBV-related HCC after liver resection. Their results support the use of antiviral therapy in the tertiary prevention of HCC. However, several issues need be clarified before extrapolating their results to other eligible patients with HBV-related HCC after curative treatment. First, curative surgical resection is usually defined by an adequate free resection margin on the resected hepatic specimen, plus no clinical or radiological evidence of tumor recurrence within 12 months after resection. However, the pathological details of surgical specimens are not included in the Taiwan database. Therefore, possible misclassification of patients with HCC as curative resection in this study may confound early or late HCC recurrence after surgery, as mentioned in the Editorial by Lok. Second, reimbursement for nucleoside analogue use in Taiwan is granted only to patients in high-risk populations and requires patients to be followed up for at least 6 months before enrollment or to have hepatic decompensation. Therefore, baseline liver disease status, remnant liver function, adherence to follow-up, and health care received may have been different between treated and untreated patients. Although the authors used complex statistical methods to adjust for possible confounding factors, these inherent differences cannot be adjusted for in their analyses. Third, according to the regulations of the Taiwan program, all treated patients need to refill anti-HBV agents monthly, suggesting the follow-up interval between the 2 groups after surgical resection may also be different. The trends in cumulative incidence rates of HCC recurrence and overall mortality were different between treated and untreated patients, even in the first year. This finding contradicts previous studies that found high viral loads and hepatic inflammatory activities to be associated with late HCC recurrence. Because the time from viral infection to tumor development is long, the markedly reduced rates of HCC recurrence and overall mortality within 1 year of curative resection are not anticipated, and there may be other possible mechanisms to explain these unusual observations.
Information Management & Computer Security Digital signatures and the future of documentation

While the business world has been moving inexorably online ever since the PC appeared, documentation itself has remained paper based for the most part. Paper of course has several major advantages including its longevity and robustness, its legal traditions, and its ability to be signed. But now the reach and speed of the Internet plus the sheer volume of business documentation is creating irresistible demand for entirely electronic documents and processes. Why should you have to wait for a hard copy to arrive by courier when you can get an e-mail instantaneously? And why should you have to re-key faxes, especially when the original almost certainly started out as a soft copy somewhere? Recent digital signature technology and associated legal analysis mean that contracts can be reliably formed online, and that purely electronic evidence can be treated the same as paper, for all legal and accounting purposes. This paper explains how digital signatures are used and online information authenticated, and paints a picture of the future documentation environment, utilising trusted electronic credentials for lawyers, doctors, accountants and so on. # KPMG Information Solutions Pty Limited 1998. All rights reserved. D ow nl oa de d by U ni ve rs ity o f N ew ca st le A t 2 2: 16 2 1 M ar ch 2 01 7 (P T ) representing an organisation. Different authorities or attributes may attach to different transactions (and so different `̀ digital personae'' may be appropriate for different types of business). At the top of the authentication staircase is `̀ Persistent ID'': the ability to prove yourself to multiple parties. This is not merely a matter of efficiency. Persistent ID is also the key to proving yourself to people who do not already know you, one of the ultimate goals of much electronic commerce. Remember that passwords only serve to identify you to an entity that already knows who (and what) you are. Document authentication (and as it happens, integrity) can be provided by digital signatures. These will be discussed sepa-
Risk factors for deaths in under‐age‐five children attending a diarrhoea treatment centre

Few case‐control studies have examined possible risk factors for diarrhoeal deaths in under‐age‐five children in the developing countries. We analysed data from the surveillance system of our diarrhoea treatment centre/hospital for the period 1990‐94 on 928 children less than 5 years of age. In univariate analysis, 11 factors were significantly associated with death: lack of breastfeeding, severe malnutrition, complicated diarrhoea, pneumonia, xerophthalmia, duration of diarrhoea 7‐14 days, moderate or severe dehydration, recent history of measles, Shigella flexneri infection, maternal illiteracy, and very low household income. Rotavirus diarrhoea was negatively associated with fatal outcome. In the assessment of severe malnutrition, weight‐for‐height measurement discriminated mortality risk better than weight‐for‐age or height‐for‐age indices. Only two factors retained their significance, severe malnutrition and non‐breastfeeding in the multivariate analysis with adjusted odds ratio (95% confidence interval) of 84.2 (9.1, 775.9) and 4.2 (1.3, 13.2) respectively.
Does prone positioning improve oxygenation and reduce mortality in patients with acute respiratory distress syndrome?

The emergence of computed tomography imaging more than 25 years ago led to characterization of acute respiratory distress syndrome (ARDS) as areas of relatively normal lung parenchyma juxtaposed with areas of dense consolidation and atelectasis. Given that this heterogeneity is often dorsally distributed, investigators questioned whether care for ARDS patients in the prone position would lead to improved mortality outcomes. This clinical review discusses the physiological rationale and clinical evidence supporting prone positioning in treating ARDS, in addition to its complications and contraindications.
Heteroplasmic conjugates formed by the fusion of starfish oocyte pairs with a 12 minute time difference in the maturation phase

Two starfish oocytes with a 12 min time difference in the maturation phase were fused together with electric pulses to make a heteroplasmic conjugate. The starfish used were Asterina pectinifera. The emergence of the first meiotic spindle and the extrusion of the polar bodies in the conjugate were timed. Under polarization microscopy two meiotic spindles emerged with a time difference of 10–11 min, which is close to the time difference in the maturation phase between the original oocytes before fusion. In contrast, subsequent formation of the first two polar bodies occurred successively with a short time lag of 1–3 min between them. Times for the formation of both polar bodies were midway between the anticipated times for polar body formation in respective non‐fused control oocytes. Thus, in one nucleus the meiotic division was delayed, while in another nucleus it was accelerated, in a single heteroplasmic conjugate. These two sets of observations indicate the presence of a certain control system that regulates progression of the cell cycle at a point during the period from the entry into metaphase through to late anaphase of meiosis I in starfish oocytes. This type of cell cycle control in starfish oocytes is obviously distinct from the currently accepted view of the cell cycle control by the spindle assembly checkpoint that monitors unattached kinetochores of mitotic chromosomes.
Learning by Ruling and Trade Disputes

Over the WTO years, the frequency of disputes and court rulings has trended downwards. Such trends are sometimes interpreted as symptoms of a dispute resolution system in decline. In this paper we propose a theory that can explain these trends as a result of judicial learning; thus according to our theory such trends represent good news, not bad news. We then offer evidence that the predictions of our model are consistent with WTO trade dispute data, and we take a first step towards estimating the strength and scope of court learning.
Influence of Dose, Cigarette Smoking, Age, Sex, and Metabolic Activity on Plasma Clozapine Concentrations: A Predictive Model and Nomograms to Aid Clozapine Dose Adjustment and to Assess Compliance in Individual Patients

Abstract: The measurement of plasma clozapine concentrations is useful in assessing compliance, optimizing therapy, and minimizing toxicity. We measured plasma clozapine and norclozapine (N-desmethylclozapine) concentrations in samples from 3782 patients (2648 male, 1127 female). No clozapine was detected in 291 samples (227 patients, median prescribed dose 300 mg/d). In 4963 (50.2 %) samples (2222 patients); plasma clozapine concentration ranged from 10 to 350 ng/mL. Step-wise backward multiple regression analysis (37 % of the total samples) of log10 plasma clozapine concentration against log10 clozapine dose (mg/d), age (year), sex (male = 0, female = 1), cigarette smoking habit (nonsmokers = 0; smokers = 1), body weight (kg), and plasma clozapine/norclozapine ratio (clozapine metabolic ratio, MR) showed that these covariates explained 48% of the observed variation in plasma clozapine concentration (C = ng/mL × 10−3) (P < 0.001) according to the following equation: This model and its associated confidence intervals were used to develop nomograms of plasma clozapine concentration versus dose for male and female smokers and nonsmokers. Predicted plasma clozapine changes by +48% in nonsmokers, +17% in females, ±8% for every 0.1 change in MR (reference 1.32), ±4% for every 5 years (reference 40 years), and ±5% for every 10 kg body weight (reference 80 kg). The nomograms can be used (i) to individualize dosage to achieve a given target plasma clozapine concentration, and (ii) for quantitative evaluation of adherence by estimating the likelihood of an observed concentration being achieved by a given dosage regimen. The model has been validated against published data.
Incidence of acute volleyball injuries: a prospective cohort study of injury mechanisms and risk factors

The purpose of the study was to examine the incidence and mechanisms of acute volleyball injuries, with particular reference to possible risk factors for ankle injuries. Coaches and players in the top two divisions of the Norwegian Volleyball Federation were asked to keep records of exposure time and all acute volleyball injuries causing a player to miss at least one playing day during one season. We found 89 injuries among 272 players during 51 588 players hours, 45 837 h of training and 5751 h of match play. The total injury incidence was 1.7 ± 0.2 per 1000 h of play, 1.5 ± 0.2 during training and 3.5 ± 0.8 during match play. The ankle (54%) was the most commonly injured region, followed by the lower back (11%), knee (8%) shoulder (8%) and fingers (7%). Of the ankle injuries, 79% were recurrences, and the relative risk of injury was 3.8 (P < 0.0001) for previously injured ankles (38 of 232) vs. non‐injured ankles (10 of the 234). Moreover, a reinjury was observed in 21 of the 50 ankles that had suffered an ankle ankle sprain within the last 6 months (42.0 ± 7.0%; risk ratio: 9.8 vs. uninjured ankles; P < 0.000001). The data indicate that external supports should be worn for 6–12 months after an ankle sprain and that specific injury prevention programs may be developed for ankle sprains in volleyball.
The 1891-1920 birth cohort of Quebec chrysotile miners and millers: mortality 1976-88.

A cohort of some 11,000 men born 1891-1920 and employed for at least one month in the chrysotile mines and mills of Quebec, was established in 1966 and has been followed ever since. Of the 5351 men surviving into 1976, only 16 could not be traced; 2508 were still alive in 1989, and 2827 had died; by the end of 1992 a further 698 were known to have died, giving an overall mortality of almost 80%. This paper presents the results of analysis of mortality for the period 1976 to 1988 inclusive, obtained by the subject-years method, with Quebec mortality for reference. In many respects the standardised mortality ratios (SMRs) 20 years or more after first employment were similar to those for the period 1951-75--namely, all causes 1.07 (1951-75, 1.09); heart disease 1.02 (1.04); cerebrovascular disease 1.06 (1.07); external causes 1.17 (1.17). The SMR for lung cancer, however, rose from 1.25 to 1.39 and deaths from mesothelioma increased from eight (10 before review) to 25; deaths from respiratory tuberculosis fell from 57 to five. Among men whose exposure by age 55 was at least 300 million particles per cubic foot x years (mpcf.y), the SMR (all causes) was elevated in the two main mining regions, Asbestos and Thetford Mines, and for the small factory in Asbestos; so were the SMRs for lung cancer, ischaemic heart disease, cerebrovascular disease, and respiratory disease other than pneumoconiosis. Except for lung cancer, however, there was little convincing evidence of gradients over four classes of exposure, divided at 30, 100, and 300 mpcf.y. Over seven narrower categories of exposure up to 300 mpcf.y the SMR for lung cancer fluctuated around 1.27 with no indication of trend, but increased steeply above that level. Mortality form pneumoconiosis was strongly related to exposure, and the trend for mesothelioma was not dissimilar. Mortality generally was related systematically to cigarette smoking habit, recorded in life from 99% of survivors into 1976; smokers of 20 or more cigarettes a day had the highest SMRs not only for lung cancer but also for all causes, cancer of the stomach, pancreas, and larynx, and ischaemic heart disease. For lung cancer SMRs increased fivefold with smoking, but the increase with dust exposure was comparatively slight for non-smokers, lower again for ex-smokers, and negligible for smokers of at least 20 cigarettes a day; thus the asbestos-smoking interaction was less than multiplicative. Of the 33 deaths from mesothelioma in the cohort to date, 28 were in miners and millers and five were in employees of a small asbestos products factory where commercial amphiboles had also been used. Preliminary analysis also suggest that the risk of mesothelioma was higher in the mines and mills at Thetford Mines than in those at Asbestos. More detailed studies of these differences and of exposure-response relations for lung cancer are under way.
Miliary nodules: An unusual presentation of allergic bronchopulmonary aspergillosis

Allergic bronchopulmonary aspergillosis (ABPA) is an immune-mediated inflammatory disease caused by hypersensitivity to Aspergillus fumigatus. A wide spectrum of plain radiographic appearances has been described in ABPA, though none are pathognomonic of ABPA. The common radiological abnormalities encountered are fleeting pulmonary opacities, bronchiectasis, and mucoid impaction. Uncommon radiological findings encountered in ABPA include pulmonary masses, perihilar opacities simulating hilar adenopathy, and pleural effusions. However, miliary nodules as a radiological presentation of ABPA are very rare and only one case has been reported in literature. It is often misdiagnosed and mismanaged as tuberculosis; thus, the clinician should be vigilant enough to diagnose this very rare entity.
Similarity-Based Diff, Three-Way Diff and Merge

Semi-structured documents and data pervade modern workflows in all areas. Collaborative work and version management rely on effective, automatic difference analysis and three-way difference analysis tools. In our effort to develop a three-way difference analysis for tree-structured documents we developed a kernel three-way difference algorithm which extends the equality-based procedures, such as GNU diff3, by considering the similarity of documents in the difference analysis as well as to ignore the order of data if that is semantically suitable. As a result we obtain difference analysis algorithms that can be more fine-tuned to the application domain. Moreover, the equality-based counter-parts of our three-way difference analysis algorithms has the idempotency property, which the current three-way diff algorithms lacks.
Potentials for Improvement of Resource Efficiency in Printed Circuit Board Manufacturing: A Case Study Based on Material Flow Cost Accounting

The pursuit of sustainable resource use by manufacturing companies is driven by resource scarcity, environmental awareness, and cost savings potentials. To address these issues, Material Flow Cost Accounting (MFCA) has been developed and applied as an effective environmental management tool. Within MFCA’s general allocation, the accounts of products and losses are overrated by weight or volume. However, such a method is incompatible with Printed Circuit Board (PCB) manufacturing because of industry characteristics in which primary inputs and products are measured by area. Based on MFCA, this case study systematically established several linear cost calculation models along the production process for capturing the actual waste flows as well as performing cost-benefit analysis. The recognition of previously ignored losses offered the incentive to find appropriate indicators to conduct cost-benefit analysis on hotspots for losses. Loss identification and analysis indicated that machining and wiring are the necessities and priorities of process optimization for resource efficiency improvement measures. Therefore, this research could not only advance the achievement of a profitable and sustainable production while improving resource efficiency at the source but could also provide support for decision making in PCB manufacturing.
USE OF THE SELECTIVE ORAL NEURAMINIDASE INHIBITOR OSELTAMIVIR TO PREVENT INFLUENZA

A BSTRACT Background Safe and effective antiviral agents are needed to prevent infection with influenza A and B viruses. Oseltamivir (GS4104), which can be administered orally, is the prodrug of GS4071, a potent and selective inhibitor of influenzavirus neuraminidases. We studied the use of oseltamivir for longterm prophylaxis against influenza in two placebocontrolled, double-blind trials at different U.S. sites during the winter of 1997–1998. Methods We randomly assigned 1559 healthy, nonimmunized adults 18 to 65 years old to receive either oral oseltamivir (75 mg given once or twice daily, for a total daily dose of 75 or 150 mg) or placebo for six weeks during a peak period of local influenzavirus activity. The primary end point with respect to efficacy was laboratory-confirmed influenza-like illness (defined as a temperature of at least 37.2°C accompanied by at least one respiratory and at least one systemic symptom). Results In the two studies combined, the risk of influenza among subjects assigned to either oncedaily or twice-daily oseltamivir (1.2 percent and 1.3 percent, respectively) was lower than that among subjects assigned to placebo (4.8 percent; P<0.001 and P=0.001 for the comparison with once-daily and twice-daily oseltamivir, respectively). The protective efficacy of oseltamivir in the two active-treatment groups combined was 74 percent (95 percent confidence interval, 53 to 88 percent) at all the sites combined and 82 percent (95 percent confidence interval, 60 to 93 percent) at sites in Virginia, where the rate of influenza infection was higher than the overall rate. For culture-proved influenza, the rate of protective efficacy in the two oseltamivir groups combined was 87 percent (95 percent confidence interval, 65 to 96 percent). The rate of laboratory-confirmed influenza infection was lower with oseltamivir than with placebo (5.3 percent vs. 10.6 percent, P<0.001). Oseltamivir was well tolerated but was associated with a greater frequency of nausea (12.1 percent and 14.6 percent in the once-daily and twice-daily groups, respectively) and vomiting (2.5 percent and 2.7 percent, respectively) than was placebo (nausea, 7.1 percent; vomiting, 0.8 percent). However, the frequency of premature discontinuation of drug or placebo was similar among the three groups (3.1 to 4.0 percent). Conclusions Oseltamivir administered daily for six weeks by the oral route is safe and effective for the prevention of influenza. (N Engl J Med 1999;341: 1336-43.)
PGE2 modulates the tetrodotoxin‐resistant sodium current in neonatal rat dorsal root ganglion neurones via the cyclic AMP‐protein kinase A cascade.

1. In current‐clamp recordings, 1 microM prostaglandin E2 (PGE2) increased the excitability of neonatal rat dorsal root ganglion neurones. The current threshold for firing was reduced, and the response to a constant suprathreshold stimulation was modified such that a single evoked action potential was converted to a train of action potentials. The excitatory action of PGE2 was still apparent when action potentials were evoked in the presence of 500 nM tetrodotoxin. 2. In voltage‐clamp experiments 1 microM PGE2 frequently increased the magnitude of the peak currents recorded, and caused a hyperpolarizing shift (of approximately 6 mV) in the activation curve for the tetrodotoxin‐resistant sodium current (TTX‐R INa). In some cells, the hyperpolarizing shift in the activation curve was accompanied by a decrease in peak conductance. PGE2 also caused a hyperpolarizing shift in the steady‐state inactivation curve for the sodium current. 3. Extracellular application of the cAMP analogue dibutyryl cAMP (dbcAMP) at a concentration of 1 mM produced effects on both the current‐voltage relationship and the steady‐state inactivation curve for the TTX‐R INa which were indistinguishable from those observed with PGE2. Prior exposure of the neurones to dbcAMP occluded the effect of a subsequent treatment with PGE2. 4. Forskolin (10 microM), a direct activator of adenylate cyclase, mimicked the effects of PGE2 and dbcAMP on TTX‐R INa. The inactive congener of forskolin, 1, 9‐dideoxyforskolin (10 microM), reduced the amplitude of TTX‐R INa, but did not evoke a hyperpolarizing shift in the activation curve. 5. Intracellular perfusion of the neurones with an inhibitor of protein kinase A inhibited the effect of PGE2 on TTX‐R INa. 6. PGE2 also reduced the amplitude of voltage‐gated potassium currents (IK), which will contribute to the excitatory action. The mechanisms underlying the changes in IK have yet to be elucidated. 7. We propose that the PGE2‐mediated increase in excitability in sensory neurones may be due, at least in part, to the cAMP‐protein kinase A‐dependent modulation of the tetrodotoxin‐resistant sodium channel.
Influence of Potassium in the Agar Medium on the Growth Pattern of the Filamentous Fungus Fusarium solani

A decrease in the concentration of K+ ions below 3 mM in agar medium which also contained starch, casein hydrolysate, MgSO4, and K2HPO4 changed the growth pattern of Fusarium solani illuminated in diurnal 12-h light/12-h dark cycles from zonation to a feathery growth mode. Rubidium or cesium ions could replace potassium, but lithium, sodium, and the bivalent alkaline earth ions could not.