Miracle-dz/UniFAR-FTUs huggingface dataset:
Pharmaceutical trials in general practice: the first 100 protocols. An audit by the clinical research ethics committee of the Royal College of General Practitioners

Abstract Objective: To assess the outcome of 100 general practice based, multicentre research projects submitted to the ethics committee of the Royal College of General Practitioners by pharmaceutical companies or their agents between 1984 and 1989. Design: Analysis of consecutive submitted protocols for stated objectives, study design, and outcomes; detailed review of committee minutes and correspondence in relation to amendment and approval; assessment of final reports submitted at conclusion of studies. Subjects: 82 finally approved protocols, embracing 34 523 proposed trial subjects and 1195 proposed general practice investigators. Main outcome measures: Success at enrolling subjects and investigators; commencement and completion data; validity of final report's assessment of efficacy, safety, tolerability, and acceptability; and method of use and dissemination of findings. Results: 18 studies were not approved and 45 had to be amended. Randomised controlled trials comprised 46 of the original submissions. Remuneration considerations, inadequate information or consent sheets, pregnancy safety, the need to discontinue existing therapy, and suboptimal scientific content were major reasons for rejecting studies or asking for amendments. Of the 82 approved studies 8 were not started. Shortfalls of investigators (of 39%) and trial subjects (of 37%) and an overall 23% withdrawal rate were responsible for a significant incidence of inconclusive results. Within the six year follow up interval, only 19 of the studies had been formally published. Conclusions: This audit identified substantial ethical concerns in the process of approving multicentre general practice pharmaceutical research. Key messages A common feature of this audit was a shortfall of investigators and trial subjects. This needs to be anticipated by those planning multicentre trials, to avoid the risk of inconclusive results. Given that the level of scientific advance resulting from such research is not high, greater regard is required for patient welfare in terms of information provision and suspension of existing therapy. Rigorously prepared and observed committee guidelines are likely to improve the quality of research protocols and reduce amendment and non-approval rates. Randomised controlled trials using comparator drugs should form the basis of multicentre general practice pharmaceutical research, which in turn should result in higher publication rates.
Toxicities Associated with 1-month Treatment with Propylthiouracil (PTU) and Methimazole (MMI) in Male Rats

Thionamides such as propylthiouracil (PTU) and methimazole (MMI) have been used for more than 50 years to treat the more common causes of thyrotoxicosis/hyperthyroidism such as Graves’ disease. Serious adverse effects associated with thionamides in humans include idiosyncratic liver damage, agranulocytosis, aplastic anemia, and vasculitis. Both prospective and retrospective clinical studies with these drugs have failed to identify predictive biomarker for these adverse effects. To assess whether rat is a good model for predicting drug-related adverse events in the liver and in the bone marrow, we conducted a comprehensive study in male rats with multiple doses of PTU and MMI. As expected, euthyroid animals became hypothyroid along with several secondary changes associated with hypothyroidism. There were slight reductions in red blood cell parameters along with some marginal effects on the bone marrow elements. However, there was no evidence of significant neutropenia and liver injury in both PTU-treated and MMI-treated cohorts. MMI-related effects were noted in the seminiferous tubules of the testes. Overall, 1-month daily treatment of euthyroid rats with PTU or MMI resulted in hypothyroidism, minor bone marrow effects, and several secondary effects associated with hypothyroidism, but without any evidence of adverse effects reported in humans including liver injury and agranulocytosis.
INTERACTIONS OF NEUROTENSIN WITH BRAIN DOPAMINE SYSTEMS *

For over a decade, our research group has studied the role of peptides in the central nervous system (CNS). In particular, we have concentrated for the last six years on characterizing the pharmacological and behavioral effects of neurotensin (NT), the tridecapeptide about which this conference has been organized. In recent years, we have increasingly focused our attention on interactions of NT and brain dopamine (DA) systems and our findings, as well as those of others, form the theme of this review. Certain aspects of this subject are also discussed by Kalivas et al.' and by Prange and NemeroffZ in this volume. As described by Luttinger et ~ 1 . ~ in this volume, our early work with centrally administered NT was concerned with characterizing the effects of the peptide on the actions of two centrally acting depressants, pentobarbital and ethanol. The peptide significantly enhanced both pentobarbitaland ethanol-induced sleeping time and ethanol-induced hypothermia. In subsequent studies, reviewed by Bissette et ~ 1 . ~ in this volume, our group demonstrated that injection of NT into cerebrospinal fluid (CSF) produced a potent hypothermia in a variety of mammals. In later studies it was shown that reduction in the functional activity of brain DA induced either by haloperidol (receptor blockade) or by 6-hydroxydopamine (DA neuronal destruction) results in a marked potentiation of NT-induced hypothermia in rats5 (FIG 1). Subsequently, Bissette et ~ 1 . ~ demonstrated that NT-induced hypothermia in mice is antagonized by the indirect DA agonists methylphenidate and d-amphetamine. While we were characterizing the effects of DA antagonists and agonists on NT-induced hypothermia, Rivier et ~ 1 . ~ reported that intravenously administered NT produced a significant increase in plasma prolactin levels, a characteristic effect of DA antagonists. These findings, along with others (see refs. 8-10), illustrate the pharmacological properties that are shared by NT and neuroleptic drugs, all of which are DA receptor blockers. Moreover, brain NT and DA perikarya and terminals are found in close proximity in a variety of brain regions (e.g., nucleus accumbens, ventral tegmentum, and hypothalamus). These observations commanded a closer examination of NT-DA interactions.
Operational tsunami modelling with TsunAWI – recent developments and applications

In this article, the tsunami model TsunAWI (Alfred Wegener Institute) and its application for hindcasts, inundation studies, and the operation of the tsunami scenario repository for the Indonesian tsunami early warning system are presented. TsunAWI was developed in the framework of the German-Indonesian Tsunami Early Warning System (GITEWS) and simulates all stages of a tsunami from the origin and the propagation in the ocean to the arrival at the coast and the inundation on land. It solves the non-linear shallow water equations on an unstructured finite element grid that allows to change the resolution seamlessly between a coarse grid in the deep ocean and a fine representation of coastal structures. During the GITEWS project and the following maintenance phase, TsunAWI and a framework of pre- and postprocessing routines was developed step by step to provide fast computation of enhanced model physics and to deliver high quality results.
Alanine aminotransferase normalization at week 8 predicts viral response during hepatitis C treatment.

AIM To investigate alanine aminotransferase (ALT) and sustained virological response (SVR) in chronic hepatitis C (CHC) during peginterferon-ribavirin treatment. METHODS One hundred and fifty-one genotype 1 CHC patients underwent treatment for 48 wk with peginterferon and ribavirin, and were retrospectively divided into two groups as having a rapid virological response (RVR) (Group 1, n = 52) and not having an RVR (Group 2, n = 99). We also subdivided each group into two according to the initial ALT level being high (Group 1h and Group 2h) or normal (Group 1n and Group 2n). HCV RNA and ALT levels were measured at baseline; at 4, 12, 24 and 48 wk during the treatment period; and at 24 wk follow-up. ALT levels were also obtained at 8 wk. According to the results of ALT, patients were enrolled in either the follow-up abnormal or follow-up normalized ALT groups at each interval. Patients with high and normal ALT levels were compared for each interval in terms of SVR. RESULTS The SVR rates were 83% vs 40% (P = 0.000), 82% vs 84% (P = 0.830), and 37% vs 44% (P = 0.466) when comparing Group 1 with 2, 1h with 1n, and 2h with 2n, respectively. In Group 2h, the SVR rates were 34% vs 40% (P = 0.701), 11% vs 52% (P = 0.004), 12% vs 50% (P = 0.007), 7% vs 50% (P = 0.003), 6% vs 53% (P = 0.001), and 0% vs 64% (P = 0.000) when comparing patients with high and normalized ALT levels at week 4, 8, 12, 24, 48 and 72, respectively. The multiple logistic regression analysis revealed that RVR (OR = 7.05; 95%CI: 3.1-16.05, P = 0.000), complete early virological response (cEVR) (OR = 17.55; 95%CI: 6.32-48.76, P = 0.000), normalization of ALT at 8 wk (OR = 3.04; 95%CI: 1.31-7.06, P = 0.008), and at 12 wk (OR = 4.21; 95%CI: 1.65-10.76, P = 0.002) were identified as independent significant predictive factors for SVR. CONCLUSION Normalization of ALT at 8 wk may predict viral response during peginterferon-ribavirin treatment in genotype-1 CHC patients especially without RVR.
All Ties are Not Created Equal: Institutional Equity Ties, IPO Performance, and Market Growth of New Ventures

This chapter examines whether and how different types of institutional ties affect new venture performance at different organizational stages. The authors propose that equity ties to government agencies will enhance the speed and returns of initial public offerings (IPOs) but hinder post-IPO market growth. By contrast, equity ties to research institutes will contribute positively to both IPO performance and post-IPO market growth. The authors build their arguments on how the two types of institutional ties meet new ventures’ need to be legitimate and competitive pre- and post-IPO. They test their hypotheses with new ventures in the pharmaceutical and chemical industries that went public in China and find supportive evidence.
Coordination of efforts in disaster relief supply chains: the moderating role of resource scarcity and redundancy

ABSTRACT Connecting to the ongoing conversation on the importance of effective coordination, in this paper, we empirically examine the impact of key theoretical modes of coordination, i.e. resource sharing, standardisation of operations, and synchronisation in disaster relief supply chains, on the performance of the humanitarian organisations. Survey data are collected from 101 humanitarian organisations in the emerging countries within Southeast Asia. Data are used to test a conceptually developed model, using structural equation modelling–partial least square (SEM-PLS) approach. The results reveal the significant impact of resource sharing and standardisation on performance outcomes in terms of resources used, responsiveness, and flexibility, while resource sharing is highly weakened by resource scarcity and redundancy. The managerial implication and recommendations are concluded for further research.
Optimal eavesdropping problem in privacy preserving consensus

In this paper, we consider the privacy preserving problem in an agreement network under interception attacks. First, we introduce a consensus protocol with privacy preserving, where each node hides their initial states into a set of random sequences, and then injects the sequences into the process of consensus. Second, we assume that an attacker with limited power can intercept the data transmitted on the edges. Aiming at the case when the privacy preserving protocol fails, we propose an index to measure the degree of network privacy leakage. In the ring and small-world network, we find an optimal attacking strategy for the attacker to maximize the probability of the privacy leakage from the perspective of the attacker. Finally, we verify all the derived theoretical results by simulations.
The Impact of Government-Guaranteed Export on Working Capital Loan Programs in Kingdom Saudi Arabia (KSA):

Abstract This paper studies the impact of government guaranteed export on (WCLPCs) working capital loan programs in Kingdom Saudi Arabia (KSA). These guarantees automatically granted to exporters firms if needed to supports them to covers their costs to prepare goods or services to importers before receive the transfer of contracting, except following method of payments in foreign trade open account or letter of credit situations. In addition, guarantee programs is not only increasing the availability of loans to small and medium enterprises (SMEs) of exporters in (KSA), but in also improving the ex-post performance of borrowing exporters firms. The government agency in charge of implementing this policy. Using propensity score matching and difference-in-differences, we found that exporters firms that funds access to credit backed by the KSA Government Funds (GFs) are able to grow in terms of both output and employment. However, we did find impact on Working Capital Loan Programs in countries from government guaranteed export. In wages, investment, inventories, assets, others need expenses of exporters firms. These results suggest that exporters firms use the new funds as working capital loan programs from government to grow their businesses before receivable the transfer from importers outside of their country rather than for investment in new durable goods that increase their capital stock. Keywords: government guaranteed export, working capital loan programs, exporters firms, contracting, and method of payment, KSA, and importers. JEL Classification: C12, G32, M41
Unsupervised diagnosis of network traffic anomalies

Les operateurs reseau doivent souvent s'occuper d'evenements qui compromettent leurs reseaux. Une approche pour trouver ces evenements est de surveiller le trafic dans un ou plusieurs liens et chercher des ecarts importants par rapport a un modele statistique du comportement normal. Ce probleme, connu sous le nom de diagnostic d'anomalies de trafic, comporte deux etapes: la detection d'anomalies, et l'analyse de leurs causes racines. Les methodes de detection d'anomalies doivent definir d'abord un modele du trafic normal. Un autre probleme avec les detecteurs actuels est qu'ils ne donnent aucune information permettant a identifier les flots de trafic responsables d'une anomalie. L'analyse des causes racines est le processus de recuperation de ce type d'information, en cherchant des evenements sur la trace de trafic qui pourraient expliquer l'alarme. Dans cette these, nous developpons un systeme de diagnostic d'anomalies (c'est-a-dire, la detection et l'analyse des causes racines) qui expose une vaste gamme d'anomalies et explique leurs causes automatiquement. Nous proposons ASTUTE, un detecteur d'anomalies qui utilise un modele de trafic non-parametrique, et donc est simple a calculer et a l'abri de la contamination des donnees. Deuxiemement, nous proposons URCA, une technique qui automatise l'analyse des causes racines. URCA identifie le trafic anormal et le classifie selon le type de cause racine. Nous faisons des nombreuses experiences afin d'evaluer la performance de ces techniques. Nos resultats montrent que ASTUTE et URCA peuvent diagnostiquer correctement une multitude d'anomalies.
The open lung during small tidal volume ventilation: concepts of recruitment and "optimal" positive end-expiratory pressure.

OBJECTIVES To test the hypotheses that during small tidal volume ventilation (5 mL/kg) deliberate volume recruitment maneuvers allow expansion of atelectatic lung units and that a high positive end-expiratory pressure (PEEP) above the lower inflection point of the pressure/volume (PV) curve is not necessarily required to maintain recruited lung volume in acute lung injury. DESIGN Prospective, randomized, controlled animal study. SETTING An animal laboratory in a university setting. SUBJECTS Adult New-Zealand rabbits. INTERVENTIONS We studied a) the relationship of dynamic loops during intermittent positive pressure ventilation to the quasi-static PV curve, and b) the effect of lung recruitment on oxygenation, end-expiratory lung volume (EELV), and dynamic compliance in two groups (n = 4 per group) of lung-injured animals (lung lavage model): 1) the sustained inflation group, which received ventilation after a recruitment maneuver (sustained inflation); and 2) the control group, which received ventilation without any lung recruitment. MEASUREMENTS AND MAIN RESULTS In the presence of PV hysteresis, a single sustained inflation to 30 cm H2O boosted the ventilatory cycle onto the deflation limb of the PV curve. This resulted in a significant increase in EELV, oxygenation, and dynamic compliance despite equal PEEP levels used before and after the recruitment maneuver. Furthermore, after a single sustained inflation, oxygenation remained high over 4 hrs of ventilation when a PEEP above the critical closing pressure of the lungs, defined as "optimal" PEEP, was used and was significantly higher compared with that in the control group ventilated at equal PEEP without preceding lung recruitment. CONCLUSIONS The observation that ventilation occurs on the deflation limb of the tidal cycle-specific PV curve allows placement of the ventilatory cycle, by means of a recruitment maneuver, onto the deflation limb of the PV envelope of the optimally recruited lung. This strategy ensures sufficient lung volume recruitment to maintain the lungs during the tidal cycle while using relatively low airway pressures.
Inter-chromosomal variation in aberration frequencies in human lymphocytes exposed to charged particles of LET between 0.5 and 55 keV/μm

Purpose: To investigate the distribution of chromosomal aberrations in chromosomes 2, 8 and 14 induced by charged particles, using the fluorescence in situ hybridisation (FISH) technique. Methods: Irradiation of peripheral blood from six healthy volunteers (four male and two female) was performed at the accelerators of the Joint Institute for Nuclear Research (JINR) in Dubna (Russia). Whole blood samples were irradiated with 2 and 3 Gy of protons (170 MeV/nucleon (n), linear energy transfer (LET) ≈ 0.5 keV/μm), 3.5 Gy of 12C ions (480 MeV/n, LET = 10.6 keV/μm), 3 Gy of 12C ions 500 MeV/n, LET = 12 keV/μm), 4 Gy of 7Li ions (30 MeV/n, LET ≈ 20 keV/μm) and 3 Gy of 11B ions (32 MeV/n, LET ≈ 55 keV/μm). Chromosomal aberrations were analysed in metaphase and prematurely condensed chromosomes (PCC) induced in G2-cells using calyculin A. Chromosomes 2, 8 and 14 were painted in different colours and aberrations scored with the help of an image-analysis system. Results: Chromosome 2 was generally less sensitive than expected on the basis of its DNA content. A higher than expected frequency of exchanges was found in chromosomes 8 and 14. On average, the dicentric frequency in chromosome 2 was higher than the translocation frequency, whereas variable dicentric to translocation ratios were observed in chromosomes 8 and 14. When aberrations in all painted chromosomes were summed up the ratio was close to 1. The frequency of complex aberrations correlated with LET. Conclusion: In lymphocytes of donors studied in this work chromosome 2 appears to be consistently less sensitive to protons and heavy ions than chromosomes 8 and 14. Complex aberrations appear to be a potential marker of radiation quality.
University of Birmingham Broadband sub-wavelength profile high-gain antennas based on multi-layer metasurfaces

• Users may freely distribute the URL that is used to identify this publication. • Users may download and/or print one copy of the publication from the University of Birmingham research portal for the purpose of private study or non-commercial research. • User may use extracts from the document in line with the concept of ‘fair dealing’ under the Copyright, Designs and Patents Act 1988 (? ) • Users may not further distribute the material nor use it for the purposes of commercial gain.
Effect of Physico-Chemical Properties on Soil Enzyme Acid Phosphatase Activity of Some Soils in Vegetable Growing Soils of Ranga Reddy District of Telangana State, India

Soil is important among all the components of terrestrial ecosystems and is a main source of production in agriculture. Since soil is a dynamic system there is a continuous reaction between soil minerals, organic matter and organisms. These reactions influences physiochemical and biological properties of soil. Soil phosphatases is one of enzyme which plays a major role in the mineralisation processes (dephosphorylation) of organic P substrates.
COINTEGRATING POLYNOMIAL REGRESSIONS: FULLY MODIFIED OLS ESTIMATION AND INFERENCE

This paper develops a fully modified OLS (FM-OLS) estimator for cointegrating polynomial regressions, i.e., regressions that include as explanatory variables deterministic variables, integrated processes, and integer powers of integrated processes. The stationary errors are allowed to be serially correlated and the regressors are allowed to be endogenous. The paper extends the fully modified estimator of Phillips and Hansen (1990) from cointegrating regressions to cointegrating polynomial regressions. The FM-OLS estimator has a zero-mean Gaussian mixture limiting distribution that allows for standard asymptotic inference. Wald and LM specification tests as well as a KPSS-type test for cointegration are derived. The theoretical analysis is complemented by a simulation study which shows that this FM-OLS estimator, as well as tests based upon it, perform well in the sense that the performance advantages over OLS are largely similar to the performance advantages of FM-OLS over OLS in standard cointegrating regressions.
Channel occupancy time distribution in a cellular radio system

The distribution of the channel occupancy time in a cellular radio system is studied, namely, the distribution of the time spent by customers on one frequency channel within a given cell. Two approaches are used. The first one relies on a computer simulation allowing a general model for mobiles behavior. The second is analytical, and assume a simplified system where mobiles keep constant directions. The results of both methods are compared with a fitted exponential distribution, and excellent agreements are found for most practical situations. In addition, a simple expression giving the average number of handoffs for a random customer is obtained. The results derived in this paper provide useful and simple tools to analyze cellular systems.