Miracle-dz/UniFAR-FTUs huggingface dataset:
Disability progression in a clinical trial of relapsing-remitting multiple sclerosis: eight-year follow-up.

OBJECTIVE To investigate the value of Expanded Disability Status Scale (EDSS) worsening sustained for at least 6 months and other parameters as predictors for disability status. DESIGN Retrospective analysis of the Multiple Sclerosis Collaborative Research Group study data. SETTING The intramuscular interferon beta-1a pivotal trial was a double-blind, placebo-controlled phase 3 study. PARTICIPANTS Patients with relapsing-remitting multiple sclerosis who received at least 2 years of treatment and completed an EDSS evaluation 8 years postrandomization. INTERVENTION Thirty micrograms of intramuscular interferon beta-1a or placebo once weekly during the 2-year clinical trial. MAIN OUTCOME MEASURES Positive predictive values for 6-month sustained progression during 2 years were calculated to determine the ability to predict disability status at 8 years. A multivariate logistic regression model was used to assess the relationship between predictors and EDSS milestones at follow-up. RESULTS Forty-five patients had sustained 6-month EDSS progression during the clinical trial and 115 did not. Progression during the trial was the strongest predictor of reaching EDSS milestones at the follow-up visit, 8 years after randomization. Other independent predictors were treatment arm assignment and baseline EDSS score. CONCLUSION In this phase 3 clinical trial of intramuscular interferon beta-1a, compared with effects of treatment, baseline EDSS score, and number of relapses during the study, worsening of 1 point or more on EDSS from baseline lasting 6 months was the strongest predictor of clinically significant disability 8 years after randomization into the clinical trial.
Policy and Technology as Factors in Industry Consolidation

Evidence of mergers, acquisitions, and strategic partnerships of firms specializing in biotechnology and the related product chain is widespread. Popular examples include the DuPont/Pioneer Hi-Bred International strategic partnership and acquisition; the purchase of Dekalb Genetics Corporation by Monsanto; the failed acquisition of Monsanto by American Home Products; the purchase of Holden Seeds by Monsanto; the consolidation of U.S. and European companies forming Norvatis; the consolidation of cooperatives and private firms specializing in grain and oil seed handling; and many others (Lerner and Merges 1997). The upshot of these mergers, acquisitions, and strategic partnerships is that there are currently many fewer major companies controlling most of the genetics and related developmental systems for supporting biotechnology advances in the production of major staple crops, and the processing and delivery systems for taking advantage of related traits. What is causing the consolidation in the biotechnology industry? Many of the explanations are peculiar to the firms involved and their special circumstances. In this paper we focus on the economic aspects of these firms, and the conditions under which they operate. In addition, we emphasize the technology and policy factors responsible for consolidation. In the case of technology, there are many angles for investigation. For instance, aspects of technology that relate to the special and complex features of research and development for biotechnology products, the technology of organizations and our improved knowledge about contracts and incentive compatibility, the growth and evolution of information technology and its impacts on the development of integrated assembly, handling and processing systems for biotechnology/derived products, the scale and scope economies that emerge from various sources, and Policy and Technology as Factors in Industry Consolidation
A heparin sulfate-regulated human keratinocyte autocrine factor is similar or identical to amphiregulin

A novel human keratinocyte-derived autocrine factor (KAF) was purified from conditioned medium by using heparin affinity chromatography as the first step. Purified KAF stimulated the growth of normal human keratinocytes, mouse AKR-2B cells, and a mouse keratinocyte cell line (BALB/MK). Heparin sulfate inhibited KAF mitogenic activity on all cell types tested and inhibited the ability of KAF to compete with epidermal growth factor for cell surface binding. Interestingly, KAF stimulated the growth of BALB/MK cells at high cell density but failed to stimulate these cells at clonal density. Protein microsequencing of the first 20 NH2-terminal amino acid residues of purified KAF revealed identity to the NH2 terminus of human amphiregulin (AR). Northern (RNA) blot analysis with AR-specific cRNA demonstrated that human keratinocytes, as well as mammary epithelial cell cultures, expressed high levels of AR mRNA. In contrast, AR mRNA was not detected in normal human fibroblasts or melanocytes and was present at reduced levels in several mammary tumor cell lines. The mitogenic activity of purified AR was also shown to be inhibited by heparin sulfate, and an AR-specific enzyme-linked immunosorbent assay (ELISA) revealed that KAF and AR are antigenically related. We have previously shown that human keratinocytes can grow in an autocrine manner. Our present study demonstrates that one of the growth factors responsible for this autocrine growth (KAF) is similar or identical to AR and that KAF and AR bioactivity can be negatively regulated by heparin sulfate.
Word Memory in Non-Psychotic Depression

Two diverging explanations can be given for the fact that depressed persons often show deficits on verbal learning tasks: (a) researchers have suggested that memory deficits are the result of interference in the transfer from short- to long-term memory; (b) other researchers have suggested that depressives may not have cognitive deficits but may instead simply show deficits in performance. The present study assessed differences in recognition memory, free recall, organization in multitrial free recall, and final free recall among short-term and long-term non-psychotic depressives (ns = 15) to determine whether such depressed adults show deficits on verbal learning tasks. No verbal learning deficits were demonstrated for 30 depressives relative to 30 nondepressives. The implications of these findings are discussed in terms of interference and the possibility that poor verbal learning in depression is a problem of performance and not learning.
Co-simulation for the design of controllers in urban drainage systems

A co-simulation framework that uses two software tools (i.e., Matlab, Python or LabVIEW, and SWMM) is presented. The co-simulation is performed thanks to a tool that has been developed, and which is the main contribution of this work. This approach uses the storm water management model (SWMM), becoming a solution to the lack of tools to test controllers for urban drainage systems (UDS). Specifically, MatSWMM, an open source framework that can be used to this end, is presented. Additionally, in order to illustrate the features of the co-simulation methodology, some of the issues of using control-oriented models (COM) are pointed out and simulated with MatSWMM, through a simple case study. To this end, and as an illustrative example of the controllers that might be implemented with the proposed tool, a linear model of the system is built and a decentralized population dynamics-based controller is tested. The results obtained show the advantages of the co-simulation tool to evaluate the control performance of these systems.
The Relationship between Employability and Training

The aim of this paper is to provide an empirical evidence about the effects that the management of continuous training have on employability (or employment stability) in the Spanish labour market. With this purpose a binary logit model with interaction effect is been used. The dependent variable includes two situations of the active workers: continuous and discontinuous employability. To distinguish between them an Employability Index Stability (ESI) was calculated taking into account two factors: time worked and job security. Various aspects of the continuous training and personal workers data are used as independent variables. The data obtained from a survey of a sample of 918 employed have revealed a relationship between the likelihood of continuous employability and continuous training received. The empirical results support the positive and significant relationship between various aspects of the training provided by firms and employability likelihood of the workers, postulate alike from a theoretical point of view. Keywords—training management, employability/employment stability, binary logit model, interaction effect, Spanish market labour.
Spontaneous Cervical Epidural Hematoma Associated With Oral Anticoagulant Therapy

A 54-year-old woman who was on anticoagulant treatment with acenocoumarol for a mitral prothesis developed a cervical spinal epidural hematoma, probably triggered by coughing fits together with supratherapeutic anticoagulation. Because of the subacute evolution of the hematoma, it was not diagnosed until the patient was admitted to the hospital with profuse hemorrhages. Given the subacute nature of the hematoma, along with the favorable evolution, conservative treatment with dexamethasone was decided upon, and it was resolved with almost no sequelae. This unusual clinical entity definitely should be suspected in patients on anticoagulants who comptain of severe localized neck pain, most often with radicular irradiation.
Comparison of Estimates between Cohort and Case–Control Studies in Meta-Analyses of Therapeutic Interventions: A Meta-Epidemiological Study

Background Observational studies are increasingly being used for assessing therapeutic interventions. Case–control studies are generally considered to have greater risk of bias than cohort studies, but we lack evidence of differences in effect estimates between the 2 study types. We aimed to compare estimates between cohort and case–control studies in meta-analyses of observational studies of therapeutic interventions by using a meta-epidemiological study. Methods We used a random sample of meta-analyses of therapeutic interventions published in 2013 that included both cohort and case–control studies assessing a binary outcome. For each meta-analysis, the ratio of estimates (RE) was calculated by comparing the estimate in case–control studies to that in cohort studies. Then, we used random-effects meta-analysis to estimate a combined RE across meta-analyses. An RE < 1 indicated that case–control studies yielded larger estimates than cohort studies. Results The final analysis included 23 meta-analyses: 138 cohort and 133 case–control studies. Treatment effect estimates did not significantly differ between case–control and cohort studies (combined RE 0.97 [95% CI 0.86–1.09]). Heterogeneity was low, with between–meta-analysis variance τ2 = 0.0049. Estimates did not differ between case–control and prospective or retrospective cohort studies (RE = 1.05 [95% CI 0.96–1.15] and RE = 0.99 [95% CI, 0.83–1.19], respectively). Sensitivity analysis of studies reporting adjusted estimates also revealed no significant difference (RE = 1.03 [95% CI 0.91–1.16]). Heterogeneity was also low for these analyses. Conclusion We found no significant difference in treatment effect estimates between case–control and cohort studies assessing therapeutic interventions.
Magnitude of bacteraemia is associated with increased mortality in non‐typhoid salmonellosis: a one‐year follow‐up study

We examined whether the number of positive bottles in a routinely used three‐bottle blood culture (BC) set predicted one‐year mortality in adult patients with non‐typhoid Salmonella (NTS). Data from 1994 through 2003 in North Jutland County, Denmark, were retrieved from health databases and medical records. We used the number of positive BC bottles as an index of magnitude of NTS bacteraemia: Index 0 (reference) patients had a negative BC coincident with an NTS‐positive faecal culture and index 1, 2, or 3 patients had increasing levels of NTS bacteraemia. For all patients and for patients with gastroenteritis we computed Kaplan‐Meier curves to summarize survival over time and Cox regression analysis to estimate mortality in crude analyses and in analyses adjusted for comorbidity and age. There were 115, 43, 21, and 41 patients with index 0, 1, 2, and 3, respectively. One‐year cumulative mortality was 4.4%, 14.0%, 28.6%, and 41.5% for indices 0 to 3. Adjusted one‐year mortality rate ratios (with 95% confidence intervals) were 1.7 (0.5–5.8), 5.2 (1.5–17.4), and 5.3 (1.9–14.9) for index 1, 2, and 3 patients, respectively. These estimates remained robust for patients with gastroenteritis. We conclude that higher magnitude of bacteraemia predicted one‐year mortality in NTS patients.
“He has a way gayer Facebook than I do”: Investigating sexual identity disclosure and context collapse on a social networking site

This study extends previous research into social networking sites (SNSs) as environments that often reduce spatial, temporal, and social boundaries, which can result in collapsed contexts for social situations. Context collapse was investigated through interviews and Facebook walkthroughs with 27 LGBTQ young people in the United Kingdom. Since diverse sexualities are often stigmatized, participants’ sexual identity disclosure decisions were shaped by both the social conditions of their online networks and the technological architecture of SNSs. Context collapse was experienced as an event through which individuals intentionally redefined their sexual identity across audiences or managed unintentional disclosure. To prevent unintentional context collapse, participants frequently reinstated contexts through tailored performances and audience separation. These findings provide insight into stigmatized identity performances in networked publics while situating context collapse within a broader understanding of impression management, which paves the way for future research exploring the identity implications of everyday SNS use.
Client and carer experience of transition home from inpatient stroke rehabilitation

Purpose: The purpose of this qualitative study was to enhance our understanding of the transition experience for clients with stroke and their carers during discharge and the first month at home. Method: Semi-structured interviews were conducted with five clients with stroke and their carers (n = 5) at 1 month after discharge from stroke rehabilitation. Questioning in the interviews explored preparation for and the experience of the transition. Inductive thematic analysis was completed with the client and carer interviews and the resultant themes were compared. Basic demographic data were collected to allow description of the participants. Results: Five clients and five carers were interviewed 1 month after discharge to home. The analysis of the client interviews yielded three themes including: rehabilitation was okay, it’s a struggle, and supports and assistance. The carer interviews also yielded three themes including: the purpose of rehabilitation, life is different now, and looking to the future. Conclusions: The clients and the carers all spoke of the positive aspects of rehabilitation but raised concerns about the limited ability to undertake daily tasks regularly and develop personalised routines in preparation for discharge. The daily routines at home were disrupted with clients taking longer to complete daily activities and carers juggling caring responsibilities with their own lifestyle. Overall, the results suggest that there is a need for stroke rehabilitation services to better prepare the clients and carers for transition to home. Implications for Rehabilitation Stroke rehabilitation should offer more opportunities for clients to participate regularly in meaningful activities in the hospital environment. It is beneficial to consider transition from the perspectives of the client and carer as a working unit. Alternate models of service delivery that increase outreach to the home environment may be beneficial.
Correlation of in vitro drug-sensitivity testing results with response to chemotherapy and survival in extensive-stage small cell lung cancer: a prospective clinical trial.

We devised a novel clinical protocol for extensive-stage small cell lung cancer (SCLC), selecting chemotherapy whenever possible on the basis of in vitro drug-sensitivity testing (DST) of individual patients' tumor specimens. Most of the specimens were obtained from metastatic sites during routine staging procedures. Increase of tumor cell number by culture in selective media usually was required before DST could be performed. We used the Weisenthal dye exclusion assay to place the seven drugs in rank order and to select the in vitro best regimen (IVBR), a three-drug combination of proved efficacy in SCLC. After initial staging and specimen acquisition, patients received etoposide and cisplatin (primary therapy) and were restaged after 12 weeks. Patients with partial or no responses and those relapsing after a complete response to primary therapy were switched to the IVBR if DST data were available. If DST data were unavailable, an empiric combination, vincristine-doxorubicin-cyclophosphamide, was administered as secondary therapy. Tumor-containing specimens were collected from 60 of the 80 patients (75%). One or more cell lines were established from 28 patients, and DST data were available from 26 patients (33% of total). Several parameters of in vitro drug sensitivity were significantly associated [two-sided P (P2) less than . 05] with clinical response to primary therapy and also with response to the IVBR and were marginally associated with length of survival (.07 less than or equal to P2 less than or equal to .08). Sixteen patients (23%) received their IVBR as secondary therapy, and four of these (25%) attained a complete response, compared with three of 43 (7%) who received an empiric regimen (P2 = .16). We concluded that (a) selection of individualized chemotherapy is labor intensive but feasible in extensive-stage SCLC; (b) DST data are associated with clinical response to primary therapy and to secondary therapy with an IVBR; and (c) further observations will be required if we are to determine whether there is a modest therapeutic benefit to administering the IVBR as a secondary therapy.
Hypernatremic dehydration resulting from inadequate breast-feeding.

Scientific evidence accumulated over the years confirms that breast milk has many advantages over formula feeding.1. 2 The difficulty of monitoring an infant9s intake from breast-feeding may occasionally lead to problems in the rare baby in whom inadequate intake of food and fluids is not apparent. In the present case, a 2-week-old infant developed severe hypernatremic dehydration. Hypernatremia has not been reported previously in a totally breast-fed infant. CASE REPORT A 3,860-gm white female infant was born to a 28-year-old primigravida mother at 40 weeks9 gestation after an uncomplicated prenatal course. The amniotic fluid was meconium stained, and cardiac decelerations were noted during oxytocm induction.
VITRECTOMY AND SILICONE OIL INJECTION IN PEDIATRIC PATIENTS

Objective: To determine the functional and anatomic results of vitrectomy with silicone oil injection in complicated retinal detachments in children. Design: A retrospective review of all records of children aged 15 years or younger who underwent vitrectomy with silicone oil injection between 1985 and 1994 in the Goldschleger eye institute. Results: Twenty‐eight eyes of 27 patients were included in the series, with a mean follow‐up time of 24 months. The underlying pathologies included penetrating injury (11 eyes), high myopia (8 eyes), choroidal coloboma (2 eyes), retinopathy of prematurity (2 eyes), and various other pathologies (5 eyes). At the end of the follow‐up, complete or partial anatomic success was obtained in 9 eyes (32%) and 3 eyes (10%), respectively. The final visual acuity was 20/400 or better in 5 eyes (18%) and hand motions or less in 19 eyes (68%). The visual acuity could not be determined in 3 eyes due to the age of the patients, and in 1 eye due to mental retardation. The worst results occurred in the perforating injury group. The usual complications associated with silicone oil occurred frequently. Conclusions: Satisfactory anatomic and functional results were obtained in a minority of the eyes included in our series. The grave prognosis was determined by the devastating nature of the external injury in the trauma cases and the severe vitreoretinal pathology in the other eyes.
The Agricultural Foundations of the Tiwanaku State: A View from the Heartland

In this essay I explore the nature, role, and significance of intensive agriculture in the ancient state of Tiwanaku, which was centered in the high plateau of southern Peru and northwestern Bolivia. Significant primary evidence that the state of Tiwanaku systematically reclaimed immense tracts of now abandoned agricultural land around the borders of Lake Titicaca is adduced and evaluated. I conclude that Tiwanaku was a dynamic, expansive state based squarely on an effective, surplus-producing system of intensive agriculture, that the intensification agricultural production through large scale reclamation of flat, seasonally inundated land along the margins of Lake Titicaca was a prime economic strategy of the Tiwanaku state, and that this strategy was devised and managed by a hierarchically organized, central government.
Structural Characterization of a Human Cytosolic NMN/NaMN Adenylyltransferase and Implication in Human NAD Biosynthesis* 210

Pyridine dinucleotides (NAD and NADP) are ubiquitous cofactors involved in hundreds of redox reactions essential for the energy transduction and metabolism in all living cells. In addition, NAD also serves as a substrate for ADP-ribosylation of a number of nuclear proteins, for silent information regulator 2 (Sir2)-like histone deacetylase that is involved in gene silencing regulation, and for cyclic ADP ribose (cADPR)-dependent Ca2+ signaling. Pyridine nucleotide adenylyltransferase (PNAT) is an indispensable central enzyme in the NAD biosynthesis pathways catalyzing the condensation of pyridine mononucleotide (NMN or NaMN) with the AMP moiety of ATP to form NAD (or NaAD). Here we report the identification and structural characterization of a novel human PNAT (hsPNAT-3) that is located in the cytoplasm and mitochondria. Its subcellular localization and tissue distribution are distinct from the previously identified human nuclear PNAT-1 and PNAT-2. Detailed structural analysis of PNAT-3 in its apo form and in complex with its substrate(s) or product revealed the catalytic mechanism of the enzyme. The characterization of the cytosolic human PNAT-3 provided compelling evidence that the final steps of NAD biosynthesis pathways may exist in mammalian cytoplasm and mitochondria, potentially contributing to their NAD/NADP pool.