Miracle-dz/UniFAR-FTUs huggingface dataset:
Embracing failure: What the Phase III progesterone studies can teach about TBI clinical trials

Abstract Background: Despite positive preclinical studies and two positive Phase II clinical trials, two large Phase III clinical trials of progesterone treatment of acute traumatic brain injury (TBI) recently ended with negative results, so a 100% failure rate continues to plague the field of TBI trials. Methods: This paper reviews and analyses the trial structures and outcomes and discusses the implications of these failures for future drug and clinical trial development. Persistently negative trial outcomes have led to disinvestment in new drug research by companies and policy-makers and disappointment for patients and their families, failures which represent a major public health concern. The problem is not limited to TBI. Failure rates are high for trials in stroke, sepsis, cardiology, cancer and orthopaedics, among others. Results: This paper discusses some of the reasons why the Phase III trials have failed. These reasons may include faulty extrapolation from pre-clinical data in designing clinical trials and the use of subjective outcome measures that accurately reflect neither the nature of the deficits nor long-term quantitative recovery. Conclusions: Better definitions of injury and healing and better outcome measures are essential to change the embrace of failure that has dominated the field for over 30 years. This review offers suggestions to improve the situation.
Gastric ring cell carcinoma metastasis to the breast : Two case reports

Metastatic tumors of breast are rare and account only for approximately 2% of all malignant breast cancers. Breast metastasis of stomach’s signet ring cell carcinoma (SRCC) is also a very rare condition. Herein, we report two rare cases of gastric SRCC metastasis to the breast. First case is a 63-year-old female patient who was admitted to our clinic with swelling in the left breast and arm with enlarged left axillary lymphadenopathy. She was diagnosed with gastric SRCC a year ago. Second case is a 65-year-old woman diagnosed with gastric SRCC who had undergone total gastrectomy two years ago, and had one-year history of operation for kruckenberg’s tumor. This patient was admitted to our clinic with two months history of pain and swelling in the left breast. She was also diagnosed as a gastric SRCC metastasis. [Turk J Cancer
AN OFF-CENTER DENSITY PEAK IN THE MILKY WAY'S DARK MATTER HALO?

We show that the position of the central dark matter (DM) density peak may be expected to differ from the dynamical center of the Galaxy by several hundred parsecs. In Eris, a high-resolution cosmological hydrodynamics simulation of a realistic Milky-Way-analog disk galaxy, this offset is 300–400 pc (∼3 gravitational softening lengths) after z = 1. In its dissipationless DM-only twin simulation ErisDark, as well as in the Via Lactea II and GHalo simulations, the offset remains below one softening length for most of its evolution. The growth of the DM offset coincides with a flattening of the central DM density profile in Eris inward of ∼1 kpc, and the direction from the dynamical center to the point of maximum DM density is correlated with the orientation of the stellar bar, suggesting a bar–halo interaction as a possible explanation. A DM density offset of several hundred parsecs greatly affects expectations of the DM annihilation signals from the Galactic center. It may also support a DM annihilation interpretation of recent reports by Weniger and Su & Finkbeiner of highly significant 130 GeV gamma-ray line emission from a region 1. °5 (∼200 pc projected) away from Sgr A* in the Galactic plane.
The Epidemiological Scale of Alzheimer’s Disease

Alzheimer’s disease (AD) has increased from a few cases in a country at the beginning of the 20th century to an incidence of recording a case every 7 seconds in the world. From a rare disease it has reached the top 8 of major health problems in the world. One of the epidemiological problems of AD is the fact that authors from different countries use different reporting units. Some report numbers to 100,000 inhabitants, others to 1,000 inhabitants and others report the total number of cases in a country. Standardization of these reports is strictly necessary. The rise in incidence and prevalence with age is known, but interesting to see is that the incidence and prevalence do not rise in a parallel manner with age as simple logic would assume. Between the ages of 60 and 90, the incidence in men increases two times and in women 41 times, prevalence increase in men is 55.25-fold and in women 77-fold. Regarding the women/men ratio, the incidence is 20.5-fold increased, and prevalence is merely 1.3936-fold increased. These numbers raise concerns about the evolution of the disease. Regarding mild cognitive impairment (MCI)/AD ratio, only about 1 in 2 people get AD (raising? ) issues about the pathogenic disease relatedness.
Testing the rationality of expectations in the Australian foreign exchange market using survey data with missing observations

This paper is concerned with testing the rationality of exchange rate expectations in the Australian foreign exchange market when there are missing observations in the survey data on expectations due to National or other holidays. The survey data analysed contains weekly observations on 1-week and 4-week ahead forecasts of the $US/$A and the Yen/$US exchange rates. The analysis proceeds by (i) examining the time series properties of the actual and expected exchange rates; (ii) investigating whether the cointegrating relationship between the actual and expected exchange rates suggested by the rational expectations hypothesis is satisfied; and (iii) for those cases where the appropriate cointegrating relationship is observed, testing for rationality using the forecast errors. In each of these steps, the problem of missing observations is addressed. Kalman filter techniques suggested by Harvey and Pierse (1984) are used to estimate the appropriate ARIMA models in each step. Results in steps (i) - (iii) are presented for two cases: when the problem of missing observations is ignored; and when appropriate techniques are used to deal with missing observations.
Ethnic Differences in Symptom Presentation of Sexually Abused Girls

ABSTRACT Although researchers have begun to examine the issue of ethnic and cultural factors in childhood sexual abuse (CSA), relatively little has been done to look at possible ethnic and cultural differences in psychological symptoms related to CSA. This study investigated the relationship between ethnicity and symptom presentation among Hispanic, African American, and Caucasian sexually abused girls. The study examined the relationship between ethnicity and depression, ethnicity and post-trauma intrusive symptoms, and ethnicity and post-trauma avoidance symptoms. Results indicated that African American girls had significantly higher levels of post-trauma avoidance symptoms than Hispanic girls, but not Caucasian girls. No significant differences were found between ethnic groups for depression or intrusive symptoms.
A Population‐Based Study of Spinal Pain Among 35‐45‐Year‐Old Individuals: Prevalence, Sick Leave, and Health Care Use

Study Design. A questionnaire was mailed to 3000 randomly selected 35‐45‐year‐old individuals in three communities in central Sweden. Objectives. To study the 1‐year prevalence of spinal pain and its ramifications in the form of pain, function, sick leave, and health care use. Summary of Background Data. Previous researchers have used a variety of definitions and populations, but primarily have investigated the occurrence of pain. Comprehensive data are needed concerning health care use, the degree of the pain problem, functional disturbances, and sick leave. Method. Participants in the study completed a questionnaire regarding spinal pain during the past year including the degree of their experienced pain, functional impairment, lost work days, and health care use. Results. A total of 2305 people (78.5%) responded to the questionnaire. Nonrespondents had similar characteristics but a slightly lower 1‐year prevalence rate than did respondents. For respondents, the prevalence of spinal pain during the past year was 66.3%, with women having a slightly higher prevalence than men. Approximately 25% of the respondents indicated that they had a substantial problem based on ratings of pain, functional impairment, and sick leave. Work absenteeism reported to the Public Social Insurance Office involved 19% of those with pain, but an additional 15% indicated unreported absenteeism. On average, those with pain visited health care providers three times during the past year, but a small number of those who experienced pain consumed large amounts of health care and illness benefits. An important gender difference was shown, such that when pain was at its worst, men took sick leave, whereas women sought health care. Conclusions. Taken together, these data indicate that spinal pain is common among 35‐45‐year‐old men and‐ women, and that it is related to marked problems for approximately one fourth of those who experience pain. Gender differences exist in the pattern of sick leave and health care use, and a small proportion of those with pain consume very large amounts of the resources. Consequently, there is a need for early, effective, preventive treatments.
Does Swedish amateur boxing lead to chronic brain damage? 3. A retrospective clinical neurophysiological study

Abstract The aim of the present study was to investigate possible chronic brain damage due to Swedish amateur boxing. Forty seven former amateur boxers, 22 with many (HM = high‐matched) and 25 with few matches (LM = low‐matched) during their career were examined and compared with two control groups of 25 soccer players and 25 track and field athletes in the same age‐range. No severe EEG abnormality was found. There was a somewhat higher incidence of slight or moderate EEG deviations among HM‐(32%, 7/22) and LM‐(36%, 9/25) boxers than among soccer players (20%, 5/25) and track and field athletes (12%, 3/25). Brain electric activity mapping (BEAM), brainstem auditory evoked potential (BAEP) and auditory evoked P 300 potential (P 300) did not differ significantly between the groups. No neurophysiological variable was correlated to the number of bouts, number of lost fights or length of boxing career. Thus, no signs of serious chronic brain damage was found among the amateur boxers or the soccer players and the track and field athletes. However, it cannot be excluded that the EEG differences between the groups may be a sign of slight brain dysfunction in some of the amateur boxers.
Design and user evaluation of a joystick-operated full-screen magnifier

The paper reports on two development cycles of a joystick-operated full-screen magnifier for visually impaired users. In the first cycle of evaluation, seven visually impaired computer users evaluated the system in comprehension-based sessions using text documents. After considering feedback from these evaluators, a second version of the system was produced and evaluated by a further six visually impaired users. The second evaluation was conducted using information-seeking tasks using Web pages. In both evaluations, the 'thinking aloud protocol' was used. This study makes several contributions to the field. First, it is perhaps the first published study investigating the use of a joystick as an absolute and relative pointing device to control a screen magnifier. Second, the present study revealed that for most of the visually impaired users who participated in the study the joystick had good spatial, cognitive and ergonomic attributes, even for those who had never before used a joystick.
Evidence-based reproductive health care in Cameroon: population-based study of awareness, use and barriers.

OBJECTIVE To estimate the prevalence of awareness and use of evidence-based reproductive health interventions and to describe the barriers associated with the use of evidence-based interventions among health providers in north-west Cameroon. METHODS In February 2004, a population-based descriptive study of the awareness and use of 13 evidence-based interventions targeted health workers providing reproductive health care. Their awareness and use of a composite of four vital interventions was also evaluated. These were peripartum use of antiretrovirals to prevent transmission of HIV, antenatal corticosteroid administration, magnesium sulfate prophylaxis and active management of placental delivery with uterotonics. In-depth interviews with key informants were conducted as part of a qualitative substudy to discover the barriers to the use of evidence-based interventions. FINDINGS Overall, 91.4% (328/359) of reproductive health workers were surveyed. Their awareness of evidence-based interventions varied from 29% for the use of antenatal corticosteroids to 97% for the use of iron and folic acid supplementation during pregnancy. Their use of these interventions ranged from 10.2% for antenatal corticosteroids to 94.8% for iron and folic acid supplementation. Only 50/322 (15.5%; 95% confidence interval (CI)=11.8-20.0) of health workers were aware of all four vital interventions, and only 12/312 (3.8%; 95% CI=2.0- 6.6) reported using all of them regularly. A total of 26 key informants participated in the qualitative substudy. A deficiency in the education and training of health workers, especially a lack of continuing education, was commonly identified as the most important barrier to their awareness of evidence-based practices. A lack of awareness and a lack of supplies and materials were the main barriers to practice. CONCLUSION The awareness and practice of important evidence-based reproductive health interventions were less than optimal. To improve maternal and perinatal outcomes both remedial programmes to enhance awareness, including continuing education for health workers, and the provision of necessary supplies are needed.
The Division of Labour, Worker Organisation, and Technological Change

The model developed in this paper explains differences in the division of labour across firms as a result of computer technology adoption. We find that changes in the division of labour can result both from reduced production time and from improved communication possibilities. The first shifts the division of labour towards a more generic structure, while the latter enhances specialisation. Although there exists heterogeneity, our estimates for a representative sample of Dutch establishments in the period 1990-1996 suggest that productivity gains have been the main determinant for shifts in the division of labour within most firms. These productivity gains have induced skill upgrading, while in firms gaining mainly from improved communication possibilities specialisation increased and skill requirements have fallen.
MCAF1 and synergistic activation of the transcription of Epstein–Barr virus lytic genes by Rta and Zta

Epstein–Barr virus (EBV) expresses two transcription factors, Rta and Zta, during the immediate-early stage of the lytic cycle. The two proteins often collaborate to activate the transcription of EBV lytic genes synergistically. This study demonstrates that Rta and Zta form a complex via an intermediary protein, MCAF1, on Zta response element (ZRE) in vitro. The interaction among these three proteins in P3HR1 cells is also verified via coimmunoprecipitation, CHIP analysis and confocal microscopy. The interaction between Rta and Zta in vitro depends on the region between amino acid 562 and 816 in MCAF1. In addition, overexpressing MCAF1 enhances and introducing MCAF1 siRNA into the cells markedly reduces the level of the synergistic activation in 293T cells. Moreover, the fact that the synergistic activation depends on ZRE but not on Rta response element (RRE) originates from the fact that Rta and Zta are capable of activating the BMRF1 promoter synergistically after an RRE but not ZREs in the promoter are mutated. The binding of Rta–MCAF1–Zta complex to ZRE but not RRE also explains why Rta and Zta do not use RRE to activate transcription synergistically. Importantly, this study elucidates the mechanism underlying synergistic activation, which is important to the lytic development of EBV.
De novo mutation of the latency‐associated peptide domain of TGFB3 in a patient with overgrowth and Loeys–Dietz syndrome features

De Novo Mutation of the Latency-Associated Peptide Domain of TGFB3 in a Patient With Overgrowth and Loeys–Dietz Syndrome Features Gabor Matyas, Paulina Naef, Martin Tollens, and Konrad Oexle* Center for Cardiovascular Genetics and Gene Diagnostics, Foundation for People with Rare Diseases, Zurich, Switzerland Zurich Center of Integrative Human Physiology, University of Zurich, Zurich, Switzerland Pediatric Cardiology, Städtisches Krankenhaus München-Schwabing, Munich, Germany Institute of Human Genetics, Technische Universität München, Munich, Germany
Macromolecular Crowding Regulates Assembly of mRNA Stress Granules after Osmotic Stress

Background: The intracellular accumulation of compatible osmolytes in hypertonic conditions reduces macromolecular crowding and ionic strength. Results: Compatible osmolytes disassemble mRNA stress granules. Hypertonic-preconditioning and gap-junction communication favor cell survival via compatible osmolyte accumulation. Conclusion: Macromolecular crowding regulates stress granule assembly and, thus, the cell fate after osmotic stress. Significance: Compatible osmolytes can promote cell survival through their action on stress granules. The massive uptake of compatible osmolytes such as betaine, taurine, and myo-inositol is a protective response shared by all eukaryotes exposed to hypertonic stress. Their accumulation results mostly from the expression of specific transporters triggered by the transcriptional factor NFAT5/TonEBP. This allows the recovery of the cell volume without increasing intracellular ionic strength. In this study we consider the assembly and dissociation of mRNA stress granules (SGs) in hypertonic-stressed cells and the role of compatible osmolytes. In agreement with in vitro results obtained on isolated mRNAs, both macromolecular crowding and a high ionic strength favor the assembly of SGs in normal rat kidney epithelial cells. However, after hours of constant hypertonicity, the slow accumulation in the cytoplasm of compatible osmolytes via specific transporters both reduces macromolecular crowding and ionic strength, thus leading to the progressive dissociation of SGs. In line with this, when cells are exposed to hypertonicity to accumulate a large amount of compatible osmolytes, the formation of SGs is severely impaired, and cells increase their chances of survival to another hypertonic episode. Altogether, these results indicate that the impact of compatible osmolytes on the mRNA-associated machineries and especially that associated with SGs may play an important role in cell resistance and adaption to hyperosmolarity in many tissues like kidney and liver.
Design strategies for GUI items with touch screen based information systems: assessing the ability of a touch screen overlay as a selection device

Touch screens are a popular method of interaction with information systems embedded in public kiosks. Typical information systems are used on desktop PCs and therefore restricted to having a mouse as the selection device used to interact with the system. The purpose of this paper is to investigate how effective a touch screen overlay is in selecting typical graphical user interface (GUI) items used in information systems. A series of tests were completed involving multi-directional point and select tasks. A mouse, being the standard selection device, was also tested so the results of the touch screen could be compared. The GUI items tested were a button, check box, combo box and a text box. The results showed that the touch screen overlay was not suitable in terms of selecting small targets with a size of 4mm or less. The touch screen overlay was slower and had higher error rate compared to the mouse. There was no significant difference in throughput between a touch screen overlay and mouse. The mouse was rated easier to use and easier to make accurate selections with. The touch screen had higher arm, wrist and finger fatigue. This indicates that a touch screen overlay used only with a finger is not a practical selection device to use with interfaces containing small targets.
Radiation doses and LET distributions of cosmic rays.

Among cosmic rays, the heavy nuclei ( HZE particles) like iron provide the dominant contribution to the dose equivalent during exposures in space. The LET distributions and radiation doses of cosmic-ray components have been calculated--with and without the quality factors--for a set of shielding and tissue self-shielding penetration depths. The relative contributions of heavy ions among solar flare particles to the dose equivalent are also explored. The transport calculations of the nuclei in air, shielding materials, and biological tissue-like material were carried out using the partial and total nuclear cross-section equations and nuclear propagation codes of Silberberg and Tsao . Outside the magnetosphere , at solar minimum, the product of the unshielded dose and the quality factors of cosmic-ray protons and heavy nuclei with atomic number Z greater than or equal to 6 are about 5 and 47 rem/year, respectively. With 4 g/cm2 aluminum shielding and at a depth of 5 cm in a biological phantom of 30 cm diameter, the respective values of the dose equivalents are about 4 and 11 rem/year. Due to the hard spectrum of cosmic rays, the attenuation of protons thus is relatively modest, while that of heavy nuclei is larger due to the larger interaction cross section. The dose equivalent of neutrons in the shielded case mentioned above is similar to that of protons. The biological risks are tentatively assessed in terms of the BEIR 1980 report. Uncertainties in risks due to possible large RBE values at low doses of high-LET radiation and due to the microbeam nature of damage by heavy ions are pointed out. Certain experiments and studies by radiobiologists are suggested for reducing the uncertainties in the estimates of the risks.
High Recovery Rate of Non-albicans Candida Species Isolated From Burn Patients With Candidemia in Iran

Background: Blood stream infections (BSIs) are major causes of morbidity and mortality in burn patients. Microorganisms responsible for BSI are generally bacteria; however, Candida spp. are the infection agents in as many as 8% of all cases. Burn wound colonization and infections are generally the first steps to systemic infection. Candidemia in burn patients has been associated with high mortality and a prolonged hospital stay. Objectives: Candidemia in burn patients has been defined as a preterminal event, leading to high morbidity and mortality rates among these patients. The aim of this study was to establish the incidence of candidemia in burn patients in Iran. Patients and Methods: We consecutively collected 405 blood samples from 113 burn patients. The yeast isolates were identified to the species level using conventional procedures. In vitro antifungal susceptibility of the Candida isolates to amphotericin B, fluconazole, voriconazole and caspofungin was performed using the Etest. Results: Twenty-seven samples (6.7%) of the blood cultures from 13 patients (12%) were positive for Candida species. Candida parapsilosis (38%) and C. tropicalis (38%) were the most commonly found Candida species, followed by C. albicans (15%) and C. guilliermondii (15%) in the patients. The incidence of candidemia was significantly correlated with increased duration of hospitalization, increased time of stay in the intensive care unit, and higher mortality. The antifungal susceptibility tests demonstrated that amphotericin B and voriconazole had the lowest minimum inhibitory concentrations (MICs) against Candida spp. Conclusions: Non-albicans Candida should be considered as significant pathogens in burned patients with candidemia.