Miracle-dz/UniFAR-FTUs huggingface dataset:
Utilizing a trauma systems approach to benchmark and improve combat casualty care.

BACKGROUND Derived from the necessity to improve the outcomes of soldiers injured on the battlefield, the U.S. military forces developed and implemented the Joint Theater Trauma System (JTTS) and the Joint Theater Trauma Registry based on U.S. civilian trauma system models. The purpose of this analysis was to develop battlefield injury outcome benchmark metrics and to evaluate the impact of JTTS-driven performance improvement interventions. METHODS To quantify these achievements, the Joint Theater Trauma Registry captured mechanistic, physiologic, diagnostic, therapeutic, and outcome data on 18,377 injured patients from January 2004 to May 2008 for analysis. Benchmarks were developed and statistically validated by using control chart methodology. RESULTS The majority (66.4%) of battlefield wounds were penetrating mechanism, 23.3% of all patients had an Injury Severity Score of > or = 16, 21.8% had a base deficit of > or = 5, 30.5% of patients required blood, and 6.8% required massive transfusion (> or = 10 units red blood cell per 24 hours). In this severely injured population from the battlefield, the JTTS developed several pertinent benchmark metrics to assess quality of care associated with postinjury complications and mortality. The implementation of 27 JTTS-developed evidenced-based clinical practice guidelines and an improved information dissemination process was associated with a decrease in aggregate postinjury complications by 54%. CONCLUSIONS Despite the numerous challenges of a global trauma system, the JTTS has set the standard for trauma care on the modern battlefield utilizing evidence-based medicine. The development of injury care benchmarks enhanced the evolution of the combat casualty care performance improvement process within the trauma system.
The location of cardiac vagal preganglionic motoneurones in the medulla of the cat.

1. Electrophysiological techniques have been used to locate the origin of preganglionic vagal motoneurones supplying the heart of the cat. 2. The right cardiac vagal branches were identified anatomically and their ability to slow the heart was assessed by electrical stimulation. Control experiments revealed that contamination of cardiac branches by bronchomotor and oesophageal efferent fibres was likely to be small. 3. Fifty‐seven neurones in the medulla were activated antidromically on stimulating the cardiac branches at up to 5 times the threshold for cardiac slowing. They had axons with conduction velocities between 3 and 15 m/sec, corresponding to B fibres. 4. None of these were located in the region of the dorsal motor nucleus of the vagus, in spite of repeated sampling there, but all were located in the region of the nucleus ambigus. Histological examination of marked neurones (forty‐six of the fifty‐seven neurones) revealed that they were associated with its principal column, rostral to the obex. 5. Sampling motoneurones of the dorsal motor nucleus revealed that most sent axons down the thoracic vagus below the cardiac branches. Only three of thirty‐three could be activated antidromically by high intensity stimulation of the cardiac branches, but on the basis of their thresholds and conduction velocities, it is argued that they were unlikely to be cardio‐inhibitory neurones. 6. It is concluded that preganglionic cardio‐inhibitory neurones arise not in the dorsal motor nucleus, but in the principal column of the nucleus ambiguus.
Trends in incidence of anal cancer and high‐grade anal intraepithelial neoplasia in Denmark, 1978–2008

The aim of the study was to determine the incidences of anal cancer and high‐grade anal intraepithelial neoplasia (AIN2/3) over time in Danish women and men. Describing the burden of anal cancer and AIN may be valuable in future evaluations of the human papillomavirus (HPV) vaccine. We included all anal cancers in the Danish Cancer Register in the period 1978–2008 and all cases of AIN2/3 in the Danish Registry of Pathology. Overall and age‐, period‐ and histology‐specific incidence rates were estimated. During the 30‐year period, 2,187 anal cancers were identified, two thirds of which were in women. Between 1978–1982 and 2003–2008, the age‐standardized incidence rate of anal cancer increased from 0.68 to 1.48 per 100,000 person‐years in women and from 0.45 to 0.80 per 100,000 person‐years in men. Although there is no systematic screening for AIN in Denmark, we nevertheless identified 608 cases of AIN2/3 during the study period. The average annual percentage change of 5% between 1998 and 2008 represents a steep increase in the incidence of AIN in both genders. Furthermore, the incidence rate of HPV‐associated anal cancers increased significantly, whereas that of non‐HPV‐associated histological types levelled out or even declined during the 30 years of observation. In women, the increase in HPV‐associated cancers was more pronounced among those under 60 years of age. Our findings indicate that vaccines against HPV might play an important role in the prevention of anal cancer and its precursor lesions.
Body size and risk of differentiated thyroid carcinomas: Findings from the EPIC study

Results from case‐control and prospective studies suggest a moderate positive association between obesity and height and differentiated thyroid carcinoma (TC). Little is known on the relationship between other measures of adiposity and differentiated TC risk. Here, we present the results of a study on body size and risk of differentiated TC based on a large European prospective study (EPIC). During follow‐up, 508 incident cases of differentiated TC were identified in women, and 58 in men. 78% of cases were papillary TC. Cox proportional hazard models were used to estimate hazard ratios (HRs). In women, differentiated TC risk was significantly associated with body mass index (BMI, kg/m2) (HR highest vs lowest quintile = 1.41, 95% CI: 1.03–1.94); height (HR = 1.61; 95% CI: 1.18–2.20); HR highest vs lowest tertile waist (HR = 1.34, 95% CI: 1.00–1.79) and waist‐to‐hip ratio (HR = 1.42, 95% CI: 1.05–1.91). The association with BMI was somewhat stronger in women below age 50. Corresponding associations for papillary TC were similar to those for all differentiated TC. In men the only body size factors significantly associated with differentiated TC were height (non linear), and leg length (HR highest vs. lowest tertile = 3.03, 95% CI: 1.30–7.07). Our study lends further support to the presence of a moderate positive association between differentiated TC risk and overweight and obesity in women. The risk increase among taller individuals of both sexes suggests that some genetic characteristics or early environmental exposures may also be implicated in the etiology of differentiated TC.
Reduced low‐voltage activated K+ conductances and enhanced central excitability in a congenitally deaf (dn/dn) mouse

We have investigated changes in the neuronal excitability of the auditory brainstem in a congenitally deaf mouse (deafness dn/dn). Whole cell patch recordings from principal neurones of the medial nucleus of the trapezoid body (MNTB) showed strikingly enhanced excitability in the deaf mice when compared to control CBA mice at 12–14 days postnatal. MNTB neurones in normal CBA mice showed the phenotypic single action potential response on depolarization in current clamp; however, recordings from CBA mice carrying the homozygous deafness mutation fired trains of action potentials on depolarization. We show here that these changes are associated with reduced functional expression of dendrotoxin‐sensitive Kv1 potassium channels. In contrast, no differences were found in voltage‐gated calcium currents between control and deaf mice. These results reveal that loss of hair cell function in the cochlea leads to changes in ion channel expression in the central nervous system and suggests that this deafness model will be an important tool in understanding central changes occurring in human congenital deafness and in exploring activity‐dependent regulation of ion channel expression.
Clinical judgement and information seeking by nurses and physicians working with cancer patients

This study examined and compared the processes of information collection and clinical judgement by nurses (n=107) and physicians (n=27) working with cancer patients. The data was collected in two university hospitals by means of a computer‐simulated case description and the thinking‐aloud method. Data interpretation was based on SPSS statistical software and the method of content analysis. Statistical differences between the two groups were tested with non‐parametric Kruskal–Wallis Anova or the Mann–Whitney U‐test. The Wilcoxon test was applied in pairwise comparisons. Independent questions were analysed by cross‐tabulation and Pearson's χ2.
A survey of the long-term impact of Brexit on the UK and the EU27 economies

This paper reviews a sample of studies on the long-term impact of Brexit on GDP and welfare for both the UK and EU economies. It considers only official and academic studies published before the end of November 2018. The paper highlights the very wide range of results, especially for the UK, reflecting great uncertainty. The negative economic impact is more limited for the EU27 and for most Member States. Small open economies closely related to the UK are more hit than others. This is the case for Ireland due to geographical proximity, for Luxembourg with its economy specialising in financial services and for Cyprus and Malta as they are Commonwealth countries. When only the trade channel of Brexit is estimated, GDP (or welfare) losses are around 1 percentage point of GDP in the Netherlands and in Belgium while these average 0.6 percentage point of GDP in the EU27. For a same Brexit scenario, the results depend on the model specifications, on the channels considered and on some key assumptions. For the UK higher GDP/welfare losses are found for reduced-form approaches, when a productivity shock is added and, also for the EU, for global value chain approaches. Higher GDP/welfare losses are also associated with higher non-tariff trade barriers. Results are sensitive to some parameters such as the reaction of trade volumes to changes in tariffs and non-tariff trade barriers (trade elasticities). Reaching a Free Trade Agreement could limit the GDP/welfare losses both for the UK and the EU Member States compared to an orderly no deal (WTO scenario). If the UK remains in the Single Market or the Customs Union, the GDP/welfare losses induced by Brexit could be even more contained. This justifies the economic interest for both the UK and the EU Member States to reach an agreement on their future relationship.
News Sentiment and Sovereign Credit Risk

We explore the impact of media content on sovereign credit risk. Our measure of media tone is extracted from the Thomson Reuters News Analytics database. As a proxy for sovereign credit risk we consider Credit Default Swap (CDS) spreads, which are decomposed into their risk premium and default risk components. We find that media tone explains and predicts CDS returns and is a mixture of noise and information. Its effect on risk premium induce a temporary change in investors’ appetite for credit risk exposure whereas its impact on the default component lead to reassessments of the fundamentals of sovereign economies. This is consistent with prevailing theories of investor over- and under reaction.
Time and feasibility of prevention in primary care

Background. Prevention is an essential task in primary care. According to primary care physicians (PCPs),lack of time is one of the principal obstacles to its performance. Objective. To assess the feasibility of prevention in terms of time by estimating the time necessary to perform all of the preventive care recommended, separately from the PCPs and patient’s perspectives, and to compare them to the amount of time available. Methods. A review of the literature identified the prevention procedures recommended in France, the duration of each procedure and its recommended frequency, as well as PCPs’ consultation time. A hypothetical patient panel size of 1000 patients, representative of the French population, served as the basis for our calculations of the annual time necessary for prevention for a PCP. The prevention time from the patient’s perspective was estimated from data collected from a previous study of a panel of 3556 patients. Results. For PCPs, the annual time necessary for all of the required preventive care was 250 hours, or 20% of their total patient time. For a patient, the annual time required for prevention during encounters with a PCP ranged from 9.7 to 26.4 minutes per year. The mean total encounter time was 75.9 minutes per year. Nearly 73% of patients had a prevention-to-care time ratio exceeding 15%. Conclusion. Feasibility thus differs substantially between patients. These differences correspond especially to disparities in the annual care time used by each patient. Specific solutions should be developed according to the patients’ utilization of care.
Analgesic effect of the neuropeptide cortistatin in murine models of arthritic inflammatory pain.

OBJECTIVE To investigate the role of the antiinflammatory neuropeptide cortistatin in chronic pain evoked by joint inflammation. METHODS Thermal and mechanical hyperalgesia was evoked in mouse knee joints by intraplantar injection of tumor necrosis factor α and intraarticular infusion of Freund's complete adjuvant, and the analgesic effects of cortistatin, administered centrally, peripherally, and systemically, were assessed. In addition, the effects of cortistatin on the production of nociceptive peptides and the activation of pain signaling were assayed in dorsal root ganglion cultures and in inflammatory pain models. The role of endogenous cortistatin in pain sensitization and perpetuation of chronic inflammatory states was evaluated in cortistatin-deficient mice. Finally, the effect of noxious/inflammatory stimuli in the production of cortistatin by the peripheral nociceptive system was assayed in vitro and in vivo. RESULTS Expression of cortistatin was observed in peptidergic nociceptors of the peripheral nociceptive system, and endogenous cortistatin was found to participate in the tuning of pain sensitization, especially in pathologic inflammatory conditions. Results showed that cortistatin acted both peripherally and centrally to reduce the tactile allodynia and heat hyperalgesia evoked by arthritis and peripheral tissue inflammation in mice, via mechanisms that were independent of its antiinflammatory action. These mechanisms involved direct action on nociceptive neurons and regulation of central sensitization. The analgesic effects of cortistatin in murine arthritic pain were linked to binding of the neuropeptide to somatostatin and ghrelin receptors, activation of the G protein subunit Gαi , impairment of ERK signaling, and decreased production of calcitonin gene-related peptide in primary nociceptors. CONCLUSION These findings indicate that cortistatin is an antiinflammatory factor with potent analgesic effects that may offer a new approach to pain therapy in pathologic inflammatory states, including osteoarthritis and rheumatoid arthritis.
Early graft dysfunction following adult-to-adult living-related liver transplantation: predictive factors and outcomes.

AIM To describe a condition that we define as early graft dysfunction (EGD) which can be identified preoperatively. METHODS Small-for-size graft dysfunction following living-related liver transplantation (LRLT) is characterized by EGD when the graft-to-recipient body weight ratio (GRBWR) is below 0.8%. However, patients transplanted with GRBWR above 0.8% can develop dysfunction of the graft. In 73 recipients of LRLT (GRBWR > 0.8%), we identified 10 patients who developed EGD. The main measures of outcomes analyzed were overall mortality, number of re-transplants and length of stay in days (LOS). Furthermore we analyzed other clinical pre-transplant variables, intra-operative parameters and post transplant data. RESULTS A trend in favor of the non-EGD group (3-mo actuarial survival 98% vs 88%, P = 0.09; 3-mo graft mortality 4.7% vs 20%, P = 0.07) was observed as well as shorter LOS (13 d vs 41.5 d; P = 0.001) and smaller requirement of peri-operative Units of Plasma (4 vs 14; P = 0.036). Univariate analysis of pre-transplant variables identified platelet count, serum bilirubin, INR and Meld-Na score as predictors of EGD. In the multivariate analysis transplant Meld-Na score (P = 0.025, OR: 1.175) and pre-transplant platelet count (P = 0.043, OR: 0.956) were independently associated with EGD. CONCLUSION EGD can be identified preoperatively and is associated with increased morbidity after LRLT. A prompt recognition of EGD can trigger a timely treatment.
Magnetic resonance imaging and different levels of Iron overload in chronic liver disease

The need for accurate and noninvasive evaluation of liver iron stores prompted us to evaluate the reliability of high‐field magnetic resonance imaging equipment in liver patients with low or moderate siderosis, given the poor results obtained using systems operating at low field strength in such cases. Twenty patients with sporadic porphyria cutanea tarda and 28 with comparable chronic liver diseases (chronic hepatitis or cirrhosis) and moderate siderosis were compared with 10 patients with idiopathic or secondary hemochromatosis and 10 healthy controls. Plasma iron profile, ferritin concentration and liver iron concentration, determined with atomic absorption spectroscopy, were matched with the magnetic resonance parameters ‐ namely, transverse relaxation time and the signal intensity for a given proton amount, obtained with equipment operating at a field strength of 1.5 T. Hemochromatosis patients with mean liver iron concentrations of 550 μmol/gm dry wt (vs. 10 μmol of controls) exhibited an impressive reduction in the signal intensity with respect to the other three groups, and this reduction prevented any further comparison with the same porphyria cutanea tarda and chronic liver disease groups, whose liver iron level was twice that of the controls. The signal intensity remained almost unchanged in the latter groups, whereas the transverse relaxation time was significantly reduced. Moreover, correlation with liver iron was significantly inverse in the case of the transverse relaxation time (n = 17, r = 0.62, p = 0.008) and direct in the case of the transverse relaxation rate. The transverse relaxation time values returned to normal in five patients who had completed an iron‐depletion program. No significant relationships between porphyrinuria (in porphyria cutanea tarda patients) or associated histological lesions (steatosis or inflammation) and the signal intensity or the transverse relaxation time were observed. We conclude that a magnetic resonance imaging system operating at higher field strength (with respect to previous studies) represents a useful, non‐invasive diagnostic tool for the evaluation of even modest liver iron overload. Under these conditions, the decrease in the transverse relaxation time is proportional to the decrease in iron. Hemochromatosis cannot be investigated under the same conditions. (HEPATOLOGY 1993; 17:997–1002.)
Evidence for neurogenic transmission inducing degenerative cartilage damage distant from local inflammation.

OBJECTIVE To investigate involvement of the nervous system in ipsilateral and contralateral joint inflammation. METHODS Freund's complete adjuvant (CFA; 1 mg or 1 microg) was injected unilaterally and the messages (a) from the hind paw to the ipsilateral and contralateral knees and (b) from one knee to the contralateral knee were analyzed. The degenerative impact of the local injury on distant cartilage was assessed using patellar proteoglycan synthesis as an indicator. Neurogenic mechanisms were blocked either by spinal cord compression or by injection of neurokinin 1 (NK-1) antagonist, or they were mimicked by intraarticular injection of substance P. The data were compared with those gathered in a model of systemic inflammation, characterized by fever and serum interleukin-6 production. RESULTS After unilateral subcutaneous injection of CFA, proteoglycan anabolism decreased bilaterally. Spinal cord compression and administration of the NK-1 antagonist inhibited the response in the contralateral limb. Following 1 mg CFA subcutaneous injection, the ipsilateral response implicated both neurogenic and systemic mechanisms, whereas the nervous system alone was implicated after 1 microg subcutaneous CFA injection. The 1 microg CFA intraarticular injection induced a degenerative contralateral signal, which was abolished by spinal cord compression and by pretreatment with the NK-1 antagonist. Intraarticular injection of 1 microg CFA also induced an ipsilateral increase of anabolism, which was enhanced by spinal cord compression. Similar results were obtained after intraarticular injections of substance P. These effects were not reproduced with turpentine treatment, a systemic model, in which spinal cord compression had no effect. CONCLUSION A unilateral inflammation can induce, by neurogenic mechanisms, distal bilateral degeneration of articular cartilage, implicating involvement of neuropeptides.
Baseline characteristics in the Aliskiren Trial in Type 2 Diabetes Using Cardio-Renal Endpoints (ALTITUDE)

Introduction: Patients with type 2 diabetes are at enhanced risk for macro- and microvascular complications. Albuminuria and/or reduced kidney function further enhances the vascular risk. We initiated the Aliskiren Trial in Type 2 Diabetes Using Cardio-Renal Endpoints (ALTITUDE). Aliskiren, a novel direct renin inhibitor, which lowers plasma renin activity, may thereby provide greater cardio-renal protection compared with angiotensin converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB) alone. Materials and methods: ALTITUDE is a randomized, double-blind, placebo-controlled study in high risk type 2 diabetic patients receiving aliskiren 300 mg once daily or placebo added to recommended cardio-renal protective treatment including ACEi or ARB, but not both. The number of patients randomized was 8606. Results: Baseline characteristics (median, IQR) are: age 65 (58, 72) years, male 68%, BMI 29.1 (25.7, 32.2) kg/m2, cardiovascular disease 47.9%, blood pressure 134.7 (126, 150)/74.3 (67, 81) mmHg, HbA1c 7.5 (6.6, 8.6)%, LDL-cholesterol 2.4 (1.9, 3.0) mmol/L, haemoglobin 130 (119, 143) g/L, serum creatinine 115 (91, 137) µmol/L, eGFR 51.7 (42, 65) ml/min per 1.73 m2, geometric mean UACR 198.9 (52, 2886) mg/g and frequency of micro/macroalbuminuria 25.7% and 58.2%. ALTITUDE is an event-driven trial to continue until 1628 patients experience a primary cardiovascular-renal event. Conclusions: ALTITUDE will determine the potential cardio-renal benefit and safety of aliskiren in combination with ACEi or ARB in high risk patients with type 2 diabetes.