Miracle-dz/UniFAR-FTUs huggingface dataset:
Sources, impacts and trends of pharmaceuticals in the marine and coastal environment

There has been a significant investment in research to define exposures and potential hazards of pharmaceuticals in freshwater and terrestrial ecosystems. A substantial number of integrated environmental risk assessments have been developed in Europe, North America and many other regions for these situations. In contrast, comparatively few empirical studies have been conducted for human and veterinary pharmaceuticals that are likely to enter coastal and marine ecosystems. This is a critical knowledge gap given the significant increase in coastal human populations around the globe and the growth of coastal megacities, together with the increasing importance of coastal aquaculture around the world. There is increasing evidence that pharmaceuticals are present and are impacting on marine and coastal environments. This paper reviews the sources, impacts and concentrations of pharmaceuticals in marine and coastal environments to identify knowledge gaps and suggests focused case studies as a priority for future research.
Predictors of outcome for children with perforated appendicitis initially treated with non-operative management.

BACKGROUND Initial non-operative therapy for children with perforated appendicitis has become increasingly popular with the advent of powerful broad-spectrum antibiotics. However, there is no consensus regarding which patients may be managed effectively with this strategy. We reviewed all children with perforated appendicitis who were treated initially with non-operative therapy to determine those characteristics that may predict a successful outcome. METHODS We reviewed the medical records of children admitted to our hospital between January 1, 2000 and May 1, 2003 with the diagnosis of perforated appendicitis. Only those who were treated initially with a single broad-spectrum antibiotic (piperacillin-tazobactam), with the intention of performing an interval appendectomy, were included in this study. Patients were divided into two groups based on whether they were managed successfully with non-operative therapy: Responders and non-responders. Non-responders were defined as patients who either did not improve with antibiotic therapy or who required appendectomy prior to their electively scheduled time (six weeks). Demographic data, duration and type of presenting symptoms, initial white blood cell count (WBC), percent bands, percent neutrophils (PMNs), computed tomography (CT) interpretation, and interventions/operations were abstracted. Categorical data were compared using Chi-square analysis or the Fisher exact test; continuous variables were compared using the Student t-test and the Mann-Whitney U-test. RESULTS Overall, 26% (19/73) of patients treated initially non-operatively required appendectomy prior to the electively scheduled date. There was no difference between responders (n = 54) and non-responders (n = 19) with respect to age, gender, initial WBC, percent bands, percent PMNs, or duration and type of presenting symptoms. However, responders were more likely to have a phlegmon on CT scan compared to non-responders (11/54 vs. 0/19, p = 0.03). Non-responders were twice as likely to undergo drainage of an abscess by interventional radiology (10/19 vs. 13/54, p = 0.02) compared to responders. Among all patients who required percutaneous drainage, the failure rate of non-operative management was 43% (10/23). CONCLUSIONS Children with perforated appendicitis can be managed effectively with nonoperative therapy, even in the presence of intra-abdominal abscesses. However, the need for abscess drainage increases the failure rate, perhaps due to inadequate source control. Those patients with a phlegmon on CT scan as opposed to an abscess, are most likely to respond to non-operative management. Initial non-operative therapy of perforated appendicitis in children is appropriate under certain clinical circumstances, especially when the body itself or interventional radiology can achieve adequate source control.
Molecular Pathogenesis of Oral Squamous Cell Carcinoma: Implications for Therapy

The development of oral squamous cell carcinoma (OSCC) is a multistep process requiring the accumulation of multiple genetic alterations, influenced by a patient’s genetic predisposition as well as by environmental influences, including tobacco, alcohol, chronic inflammation, and viral infection. Tumorigenic genetic alterations consist of two major types: tumor suppressor genes, which promote tumor development when inactivated; and oncogenes, which promote tumor development when activated. Tumor suppressor genes can be inactivated through genetic events such as mutation, loss of heterozygosity, or deletion, or by epigenetic modifications such as DNA methylation or chromatin remodeling. Oncogenes can be activated through overexpression due to gene amplification, increased transcription, or changes in structure due to mutations that lead to increased transforming activity. This review focuses on the molecular mechanisms of oral carcinogenesis and the use of biologic therapy to specifically target molecules altered in OSCC. The rapid progress that has been made in our understanding of the molecular alterations contributing to the development of OSCC is leading to improvements in the early diagnosis of tumors and the refinement of biologic treatments individualized to the specific characteristics of a patient’s tumor.
The complex relationship between transparency and accountability: A synthesis and contribution to existing frameworks

Accountability and transparency are of growing importance in contemporary governance. The academic literature has broadly studied the two concepts separately, defining and redefining them, putting them into various frameworks, and sometimes mistakenly using them as synonyms. Curiously, the relationship between the two concepts has been studied only by a few scholars with preliminary approaches. This theoretical article focuses on both concepts, attempting first to describe them, taking into account the various evolutions in the literature and recent developments, and also the first attempts to link the two concepts. In order to show a new approach linking the concepts, theoretical situations in which the concepts are linked are portrayed, demonstrating the need to reconsider the relationship between transparency and accountability. Consequently, a new framework amending the most recent approaches is presented, theoretically delimited and exemplified through practical cases.
Milk Production in India Rises by a Historic 6.25% I2014-15: A Boon or a Bane?

Milk production in India has risen by a historic 6.25% in 2014-15, reaching 146 million tonne. This increase is indeed a boon if it can be sustained as there is an urgent need to increase the growth rate in milk production, to meet the growing domestic market for milk and milk products and ensure that India remains self-sufficient in milk. However, this high incremental growth rate was limited to only three states while the largest milk producing state Uttar Pradesh showed a constant but below the national level of growth. Further, growth in population of adult female bovines seems to be tapering off with a very low increase in productivity per animal. Hence, this is a good time and opportunity to analyse the growth in milk production. We analyse the growth in terms of supply, demand and price of milk as well price and buffer stock of skim milk powder and its role in maintaining the price at consumer and farmer end. In the short-term, with no immediate market for the incremental quantity within or outside India, much of the incremental quantity is being processed and stored as skim milk powder and butter. This is causing financial strain on the milk purchasers forcing them to reduce their demand and price for fresh milk. As a result, this high growth may be only strengthening the oligopolic market power of milk processors and/or marketers the market structure gives them, over both consumers and milk producers. The constant increase in consumer price is also not expected to be transmitted to the producer, as in a perfectly competitive market. Therefore, this high rate of growth in milk production is boon in the long term helping India remain self-sufficient in milk. However, as the farm gate prices have not only reduced but also become highly volatile making dairy animal rearing high risk venture with uncertain, it is a bane in the short term.
A Role for CD2 Antibodies (BTI-322 and its Humanized Form) in the in vivo Elimination of Human T Lymphocytes Infiltrating an Allogeneic Human Skin Graft in SCID Mice: An Fc&ggr; Receptor-Related Mechanism Involving Co-Injected Human NK Cells

Background. Pilot clinical studies have shown that the rat anti-human-CD2 monoclonal antibody, LoCD2a/BTI-322, can efficiently prevent and treat acute kidney rejection. However, the in vivo mechanism by which it prevents allograft rejection has not been studied. BTI-322 and its humanized form have been shown to mediate in vitro antibody-dependent cell-mediated cytotoxicity (ADCC) against CD2+ cells through the activation of monocytes or natural killer (NK) cells. Methods. Human fetal skin samples were grafted into severe combined immunodeficient/nonobese diabetic mice. Five weeks later (day 0), the mice were injected with human allogeneic peripheral blood lymphocytes (PBL). Either on day 0 or on day 14, mice were treated with BTI-322, hu-BTI-322, or their F(ab’)2 fragments. Peripheral blood mononuclear cells (PBMC) thoroughly devoid of NK cells were also assayed. Results. After injection of PBL, the human skins became heavily infiltrated with activated human T lymphocytes, resulting in dermal microvascular injuries indicative of graft rejection. Early treatment with BTI-322 and hu-BTI-322 prevented all these events. These CD2 antibodies rapidly eliminated human T lymphocytes that had already infiltrated the grafts, with no evidence of recirculation toward the spleen. Their F(ab’)2 fragments were, in contrast, ineffective. Elimination of NK cells from injected PBMC prevented the curative effect exerted by whole CD2 antibodies. It also abrogated their cytotoxicity potential against CD2+ cells in ADCC assays. Conclusion. F(ab’)2 fragments of the CD2 antibodies could not prevent allograft rejection, whereas whole immunoglobulin G could, and human NK cells were required for the curative effect exerted by these antibodies. The results are consistent with an Fc&ggr;R-dependent ADCC mechanism mediated in vivo by human NK cells.
Prevalence of human T-cell lymphotropic virus type 1 (HTLV-1) and HTLV-2 infection among Spanish drug users measured by HTLV-1 assay and HTLV-1 and -2 assay. HTLV-1 and HTLV-2 Spanish Study Group

The prevalence of human T-cell lymphotropic virus type 1 (HTLV-1) and HTLV-2 infection in 1992 and 1993 was determined by testing 2,152 specimens from injection drug users living in 11 geographic areas in Spain. Results obtained by an authentic HTLV-1 and -2 test were compared with those obtained by an HTLV-1 assay. HTLV infection was identified in 7 of 11 regions, with an overall prevalence of 2.5% (range, 0.4 to 11.5%). Fourty-four (81%) of 54 subjects were infected with HTLV-2; the viral strains in the remaining 10 subjects could not be serologically typed. Underestimation of HTLV infection because of the low sensitivities of HTLV-1 enzyme immunoassays for HTLV-2 antibody was relatively low (< 20%). Therefore, previous epidemiologic findings generated with HTLV-1 enzyme immunoassays appear to be reasonably accurate. Our results suggest that the rate of HTLV infection may have been increasing recently among Spanish drug users.
GPS/GLONASS receiver in land vehicle: Expectations and reality

MStar Semiconductor (Taiwan) completed design & engineering of a combined GPS/GLONASS receiver for consumer market. The purpose of this paper is to inform the GNSS community about this development; in particular, about specific features and architecture of the receiver. First results of preliminary GPS/GLONASS receiver drive tests in a land vehicle under restricted satellite visibility conditions are also presented.
Shaker Mutants Lack Post‐tetanic Potentiation at Motor End‐plates

The two‐electrode voltage clamp technique was employed to measure end‐plate currents in larval neuromuscular junctions of wild‐type (Canton‐S) and of three different Drosophila Shaker mutants: ShakerKS133, Shaker102 and f5Shaker5. In the Shaker mutants, nerve‐evoked end‐plate currents (neepc) were 4–5‐fold larger than those measured in Canton‐S. Shaker motor end‐plates were found to lack post‐tetanic potentiation (PTP), but could undergo facilitation. Moreover, PTP but not facilitation was lost in wild‐type larvae if the neuromuscular junction was exposed to 4‐aminopyridine (4‐AP), a blocker of Shaker A‐type K+ currents. End‐plate currents were depressed by Ca2+ channel blockers like Mg2+, at millimolar concentrations, and Co2+ and Cd2+, at micromolar concentrations, but not by nifedipine (100 nM) and verapamil (100 nM). After exposure to Ca2+ channel blockers, Shaker end‐plates exhibited PTP. In particular, Cd2+ was most effective in depressing neepes and in restoring PTP in all Shaker mutants. The results obtained indicate the abnormal function of Shaker K+ channels at motor nerves specifically abolishes PTP in Drosophila larval neuromuscular junctions.
Recurrent CT, cumulative radiation exposure, and associated radiation-induced cancer risks from CT of adults.

PURPOSE To estimate cumulative radiation exposure and lifetime attributable risk (LAR) of radiation-induced cancer from computed tomographic (CT) scanning of adult patients at a tertiary care academic medical center. MATERIALS AND METHODS This HIPAA-compliant study was approved by the institutional review board with waiver of informed consent. The cohort comprised 31,462 patients who underwent diagnostic CT in 2007 and had undergone 190,712 CT examinations over the prior 22 years. Each patient's cumulative CT radiation exposure was estimated by summing typical CT effective doses, and the Biological Effects of Ionizing Radiation (BEIR) VII methodology was used to estimate LAR on the basis of sex and age at each exposure. Billing ICD9 codes and electronic order entry information were used to stratify patients with LAR greater than 1%. RESULTS Thirty-three percent of patients underwent five or more lifetime CT examinations, and 5% underwent between 22 and 132 examinations. Fifteen percent received estimated cumulative effective doses of more than 100 mSv, and 4% received between 250 and 1375 mSv. Associated LAR had mean and maximum values of 0.3% and 12% for cancer incidence and 0.2% and 6.8% for cancer mortality, respectively. CT exposures were estimated to produce 0.7% of total expected baseline cancer incidence and 1% of total cancer mortality. Seven percent of the cohort had estimated LAR greater than 1%, of which 40% had either no malignancy history or a cancer history without evidence of residual disease. CONCLUSION Cumulative CT radiation exposure added incrementally to baseline cancer risk in the cohort. While most patients accrue low radiation-induced cancer risks, a subgroup is potentially at higher risk due to recurrent CT imaging.
Mutational analysis and NMR studies of the death domain of the tumor necrosis factor receptor-1.

Tumor necrosis factor receptor-1 (TNFR-1) death domain (DD) is the intracellular functional domain responsible for the receptor signaling activities. To understand the transduction mechanism of TNFR-1 signaling we performed structural and functional analysis of the TNFR-DD. The secondary structure of the TNFR-DD shows that it consists of six anti-parallel alpha-helices. The determination of the topological fold and an extensive mutagenesis analysis revealed that there are two opposite faces that are involved in self-association and interaction with the TRADD death domain. Interestingly, the same critical residues in TNFR-DD are involved in both interactions. There is a good correlation between the binding activities of the mutant proteins and their cytotoxic activities. These results provide important insight into the molecular interactions mediating TNFR-DD self-association and subsequent recruitment of TRADD in the signaling activity of TNFR-1.
Special Issue on Design and Development: A Cross-Functional Approach to Evaluating Multiple Line Extensions for Assembled Products

Assembled product manufacturers often introduce line extensions that share components with existing products, or among themselves, resulting in cost interactions among products because of shared costs, and revenue interactions because of cannibalization. We present a cross-functional approach to evaluating multiple line extensions that simultaneously considers revenue implications of component sharing at the product level and cost implications at the component level. We develop a source-of-volume model and a measurement procedure to decompose the life-cycle sales volume from a line extension into sales from cannibalization, competitive draw, and demand expansion. We develop an activity-based costing procedure for estimating the life-cycle costs of line extensions that share components. We develop an optimization model that uses these revenue and cost estimates to identify a subset of line extensions that maximizes incremental profits. We implement our approach at a quartz wristwatch manufacturer. Results suggest that our approach would have improved profits for the firm by over 5%, while actually launching fewer line extensions. We also find that the drivers of cannibalization are counterintuitive. In simulation studies, our approach outperforms three managerial heuristics. We demonstrate that this approach is most valuable when cannibalization dominates competitive draw as a source of volume, and discuss its relative merits under low and high parts-sharing.
Managing Knowledge and Information by Students

The concept of Personal Knowledge and Information Management (PKIM) is based, among others, on two theories: Personal Information Management (PTM) and Personal Knowledge Management (PKM), which hitherto were both subjects of separate studies. Moreover, the concept of PKIM is related to IL, which is a concept of information skills and competences of individuals — a person who manages knowledge has to be information literate. Some of the empirical studies results in the field of PKIM, started in Poland and recently continued in Germany, are presented. As the research method an unstructured questionnaire with open questions was used.Given the results of the survey as well as taking into account the subject literature, the concepts of PIM, PKM, and Information Literacy (IL) seem to be compatible and connected with each other. Our respondents perceive Knowledge and Information as well as knowledge management (KM) and information management (IM) in the context of learning and studying as integrated areas of interests. Although they do see differences between them, interconnections and relations seem more important. Furthermore, KM and IM are recognized as tools of coping with information overload. All aspects that have repercussions on KM and IM are related to three categories: personal characteristics, environment (macro and micro environment), and knowledge and information sources.
Adiposity and risk of thyroid cancer: a systematic review and meta‐analysis

Thyroid cancer incidence has increased rapidly over time, as has obesity prevalence. A link between the two appears plausible, but the relation of adiposity to thyroid cancer remains incompletely understood. We performed a meta‐analysis of adiposity measures and thyroid cancer using studies identified through October 2014. Twenty‐one articles yielded data on 12,199 thyroid cancer cases. We found a statistically significant 25% greater risk of thyroid cancer in overweight individuals and a 55% greater thyroid cancer risk in obese individuals as compared with their normal‐weight peers. Each 5‐unit increase in body mass index (BMI), 5 kg increase in weight, 5 cm increase in waist or hip circumference and 0.1‐unit increase in waist‐to‐hip ratio were associated with 30%, 5%, 5% and 14% greater risks of thyroid cancer, respectively. When evaluated by histologic type, obesity was significantly positively related to papillary, follicular and anaplastic thyroid cancers, whereas it revealed an inverse association with medullary thyroid cancer. Both general and abdominal adiposity are positively associated with thyroid cancer. However, relations with BMI vary importantly by tumour histologic type.
Nitric oxide regulation of tissue free radical injury.

We have presented evidence from a broad range of chemical, cell biological, and in vivo studies showing that . NO can mediate tissue-protective reactions during oxidant stress, as well as toxic and tissue prooxidant effects. One predominant factor that has been identified which influences . NO being protective versus toxic is the relative rates of production and concentrations of . NO and the more "traditional" family of reactive oxygen species, including O2. -, H2O2, . OH, LO. , LOO. , and high valency complexes of iron. Also, since so many anti-neutrophil actions of . NO have been described, it is likely that . NO will serve a protective role in acute inflammatory reactions. One issue is certain--many new truths remain to be revealed, as we continue to develop our understanding of the toxicology of reactive oxygen- and nitrogen-containing species.
Cumulative 5‐year diagnoses of CIN2, CIN3 or cervical cancer after concurrent high‐risk HPV and cytology testing in a primary screening setting

The aim of our study was to assess the cumulative 5‐year diagnoses of CIN2, CIN3 or invasive cervical cancer (CIN2+) after concurrent screening by high‐risk HPV test and Pap smear in a primary screening setting. Four thousand thirty‐four women from Eastern Thuringia/Germany were recruited from 1996 to 1998 for baseline screening that included routine cytology, high‐risk HPV testing by consensus primer PCR GP5+/6+ and routine colposcopy. After a median of 59 months 3,153 women participated in final screening using identical methods. Women with abnormal cytology or colposcopy or a positive high‐risk HPV test at any time during the study period were recalled for expert colposcopy and histologic verification. CIN2+ was detected in 160 women resulting in a cumulative 5‐year proportion of 4.4% (95% CI: 3.7–5.0%). Of 3,702 women who were high‐risk HPV negative at baseline, 34 (1.1–95% CI: 0.7–1.4%) had either prevalent CIN2+ or developed CIN2+ within the observation period. HPV/cytology double negatives at baseline were at lowest risk for CIN2+ (1.0–95% CI: 0.7–1.4%) compared to screening positives (16.8–100% depending on combined test results). The 5‐year negative predictive value in HPV−/Cyto− women was 99.0% (95% CI: 98.6–99.3%). This suggests that a prolongation of the screening intervals in this group is feasible. However, it should be noted that 1 woman developed a microinvasive carcinoma within the observation period. Moreover, 2 women with prevalent cancer were missed by both tests. The prognostic relevance of concurrent high‐risk HPV/cytology screening needs to be verified further by randomized trials. © 2005 Wiley‐Liss, Inc.