Miracle-dz/UniFAR-FTUs huggingface dataset:
Organization of medullary adrenergic and noradrenergic projections to the periaqueductal gray matter in the rat

The periaqueductal or midbrain central gray matter (CG) in the rat contains a dense network of adrenergic and noradrenergic fibers. We examined the origin of this innervation by using retrograde and anterograde axonal tracers combined with immunohistochemistry for the catecholamine biosynthetic enzymes tyrosine hydroxylase (TH), dopamine β‐hydroxylase (DBH), and phenylethanolamine N‐methyltransferase (PNMT). Following injections of the fluorescent tracers Fast Blue or Fluorogold into the CG, double‐labeled neurons in the medulla were identified mainly in the noradrenergic A1 group in the caudal ventrolateral medulla (VLM) and A2 group in the medial part of the nucleus of the solitary tract (NTS); and in the adrenergic C1 group in the rostral ventrolateral medulla and C3 group in the rostral dorsomedial medulla. Injections of Phaseolus vulgaris‐leucoagglutinin (PHA‐L) into these cell groups resulted in a distinct pattern of axonal labeling in various subdivisions of the CG. Anterogradely labeled fibers originating in the medial NTS were predominantly found in the lateral portion of the dorsal raphe nucleus and in the adjacent part of the lateroventral CG (CGlv). Following PHA‐L injections into the C3 region the anterogradely labeled fibers were diffusely distributed in the CGlv and the dorsal raphe nucleus at caudal levels, but rostrally tended to be located laterally in the CGlv. In contrast, ascending fibers from the caudal and rostral VLM terminated in the rostral dorsal part of the CGlv and in the dorsal nucleus of the CG, whereas ventral parts of the CG, including the dorsal raphe nucleus, contained few afferent fibers. Double‐label studies with antisera against DBH and PNMT confirmed that noradrenergic neurons in the A1 and A2 groups and adrenergic neurons in the C1 and C3 groups contributed to these innervation patterns in the CGlv. Noradrenergic and adrenergic projections from the medulla to the CG may play an important role in a variety of autonomic, sensory and behavioral processes.
Prenatal diagnosis of a mosaic 46,XY/47,X,i (Xq)Y

A case of mosaic 46,XY/47,X,i(Xq)Y is diagnosed at 18 gestational weeks in amniotic fluid cells and confirmed at birth in the lymphocytes of the child. The literature on Klinefelter's syndromes with structural chromosome X rearrangements is reviewed. This is the first case reported of a mosaic isochromosome Xq in a boy.
Corporate Credit Risk Changes: Common Factors and Firm-Level Fundamentals

This paper provides new evidence on the empirical success of structural models in explaining corporate credit risk changes. A parsimonious set of common factors and firm-level fundamentals, inspired by structural models, explains more than 54% (67%) of the variation in credit spread changes for medium (low) grade bonds. No dominant latent factor is present in the unexplained variation. While our set of variables has lower explanatory power among high-grade bonds, it does capture most of the systematic variation of credit spread changes in that category as well. It also subsumes the explanatory power of the Fama and French (1993) factors among all grade classes.
Subjective Memory Complaints and Cognitive Impairment in Older People

Subjective memory complaints (SMCs) are common in older people and are often thought to indicate cognitive impairment. We reviewed research on the relationship between SMCs and (a) current cognitive function, (b) risk of future cognitive decline, and (c) depression and personality. SMCs were found to be inconsistently related to current cognitive impairment but were more strongly related to risk of future cognitive decline. However, SMCs were consistently related to depression and some personality traits, e.g. neuroticism. In conclusion, the determinants of SMCs are complex. The utility of SMCs in the diagnosis of pre-dementia states (e.g. mild cognitive impairment) is uncertain and requires further evaluation.
Factors and outcomes associated with ultra-early surgery for poor-grade aneurysmal subarachnoid haemorrhage: a multicentre retrospective analysis

Objective To determine factors and outcomes associated with ultra-early surgery for poor-grade aneurysmal subarachnoid haemorrhage (aSAH). Design A multicentre retrospective analysis, observational study. Setting High-volume teaching hospitals (more than 150 aSAH cases per year). Participants 118 patients with World Federation of Neurosurgical Societies (WFNS) grades IV and V underwent surgical treatment. Ultra-early surgery was defined as surgery performed within 24 h of aSAH, and delayed surgery as surgery performed after 24 h. Outcome was assessed by modified Rankin Scale (mRS). The mean time of follow-up was 12.5±3.4 months (range 6–28 months). Results 47 (40%) patients underwent ultra-early surgery, and 71 (60%) patients underwent delayed surgery. Patients with WFNS grade V (p=0.011) and brain herniation (p=0.004) more often underwent ultra-early surgery. Postoperative complications were similar in ultra-early and delayed surgery groups. Adjusted multivariate analysis showed the outcomes were similar between the two groups. Multivariate analysis of predictors of poor outcome, ultraearly surgery was not an independent predictor of poor outcome, while advanced age, postresuscitation WFNS V grade, intraventricular haemorrhage, brain herniation and non-middle cerebral artery (MCA) aneurysms were associated with poor outcome. Conclusions Although patients with WFNS grade V and brain herniation more often undergo ultra-early surgery, postoperative complications and outcomes in selected patients were similar in the two groups. Patients of younger age, WFNS grade IV, absence of intraventricular haemorrhage, absence of brain herniation and MCA aneurysms are more likely to have a good outcome. Ultra-early surgery could improve outcomes in carefully selected patients with poor-grade aSAH.
Structure‐function relationships in rat brainstem subnucleus interpolaris: III. Local circuit neurons

Intracellular recording, electrical stimulation, receptive field mapping, and intracellular injection of horseradish peroxidase were used to assess the response properties, collateral projections, and morphology of 44 local circuit (LC) neurons in the subnucleus interpolaris (SpVi) of the trigeminal brainstem complex of the rat. LC neurons were defined as those with axons restricted to brainstem areas receiving trigeminal primary afferent fibers. Thus, none were antidromically activated from the thalamus, tectum, or cerebellum, and their axons could be seen terminating exclusively within the trigeminal brainstem complex or reticular formation. All neurons sampled were discharged by innocuous or noxious mechanical stimulation of a restricted portion of the face or mouth. They were classified functionally as sensitive to vibrissae (N = 22), nociceptors (N = 9), guard hairs (N = 7), hairy skin (N = 3), or periodontia (N = 3). Fifty percent of the stained neurons were vibrissa sensitive. Twenty‐one of these 22 responded to deflection of only one vibrissa. The remaining functional groups also had small receptive fields.
MRI-Guided Stereotactic System for Delivery of Intraspinal Microstimulation

Study Design. Laboratory/animal-based proof of principle study. Objective. To validate the accuracy of a magnetic resonance imaging (MRI)-guided stereotactic system for intraspinal electrode targeting and demonstrate the feasibility of such a system for controlling implantation of intraspinal electrodes. Summary of Background Data. Intraspinal microstimulation (ISMS) is an emerging preclinical therapy, which has shown promise for the restoration of motor function following spinal cord injury. However, targeting inaccuracy associated with existing electrode implantation techniques remains a major barrier preventing clinical translation of ISMS. Methods. System accuracy was evaluated using a test phantom comprised of nine target locations. Targeting accuracy was determined by calculating the root mean square error between MRI-generated coordinates and actual frame coordinates required to reach the target positions. System performance was further validated in an anesthetized pig model by performing MRI-guided intraspinal electrode implantation and stimulation followed by computed tomography of electrode location. Finally, system compatibility with a commercially available microelectrode array was demonstrated by implanting the array and applying a selection of stimulation amplitudes that evoked hind limb responses. Results. The root mean square error between actual frame coordinates and software coordinates, both acquired using the test phantom, was 1.09 ± 0.20 mm. Postoperative computed tomography in the anesthetized pig confirmed spatially accurate electrode placement relative to preoperative MRI. Additionally, MRI-guided delivery of a microwire electrode followed by ISMS evoked repeatable electromyography responses in the biceps femoris muscle. Finally, delivery of a microelectrode array produced repeatable and graded hind limb evoked movements. Conclusion. We present a novel frame-based stereotactic system for targeting and delivery of intraspinal instrumentation. This system utilizes MRI guidance to account for variations in anatomy between subjects, thereby improving upon existing ISMS electrode implantation techniques. Level of Evidence: N/A
Transient Receptor Potential Ankyrin 1 Channel Localized to Non-Neuronal Airway Cells Promotes Non-Neurogenic Inflammation

Background The transient receptor potential ankyrin 1 (TRPA1) channel, localized to airway sensory nerves, has been proposed to mediate airway inflammation evoked by allergen and cigarette smoke (CS) in rodents, via a neurogenic mechanism. However the limited clinical evidence for the role of neurogenic inflammation in asthma or chronic obstructive pulmonary disease raises an alternative possibility that airway inflammation is promoted by non-neuronal TRPA1. Methodology/Principal Findings By using Real-Time PCR and calcium imaging, we found that cultured human airway cells, including fibroblasts, epithelial and smooth muscle cells express functional TRPA1 channels. By using immunohistochemistry, TRPA1 staining was observed in airway epithelial and smooth muscle cells in sections taken from human airways and lung, and from airways and lung of wild-type, but not TRPA1-deficient mice. In cultured human airway epithelial and smooth muscle cells and fibroblasts, acrolein and CS extract evoked IL-8 release, a response selectively reduced by TRPA1 antagonists. Capsaicin, agonist of the transient receptor potential vanilloid 1 (TRPV1), a channel co-expressed with TRPA1 by airway sensory nerves, and acrolein or CS (TRPA1 agonists), or the neuropeptide substance P (SP), which is released from sensory nerve terminals by capsaicin, acrolein or CS), produced neurogenic inflammation in mouse airways. However, only acrolein and CS, but not capsaicin or SP, released the keratinocyte chemoattractant (CXCL-1/KC, IL-8 analogue) in bronchoalveolar lavage (BAL) fluid of wild-type mice. This effect of TRPA1 agonists was attenuated by TRPA1 antagonism or in TRPA1-deficient mice, but not by pharmacological ablation of sensory nerves. Conclusions Our results demonstrate that, although either TRPV1 or TRPA1 activation causes airway neurogenic inflammation, solely TRPA1 activation orchestrates an additional inflammatory response which is not neurogenic. This finding suggests that non-neuronal TRPA1 in the airways is functional and potentially capable of contributing to inflammatory airway diseases.
Insights into breast cancer: New familial patterns and identification of a potential predictive marker

The last proportion of heredity in breast cancer has proven to be somewhat elusive despite massive attempts to identify the associated factors. Approximately 50 percent of breast cancer caused by familial factors is currently explained. The five-year survival for breast cancer patients is excellent; however, breast cancer is considered a chronic disease, and given enough time, new tumors can develop. Women age 40 and older are offered screening mammography. However, population screening is expensive, and being able to pinpoint those who are at high risk of breast cancer would be beneficial. Both genetic and environmental risk factors could be used to select women who need screening. A major aim of this thesis was to try to identify potential familial patterns as candidates for hereditary breast cancer. In Paper I, we studied horizontal family history of breast cancer in relation to histology to discover a candidate phenotype for recessive inheritance. A horizontal pedigree pattern is characterized by two or more sisters diagnosed with breast cancer, without a family history of breast cancer in prior generations. A horizontal inheritance was more common in patients with tubular carcinoma compared with other histologic subtypes. Therefore, we propose that breast cancer patients with tubular carcinoma who have a sister or sisters diagnosed with breast cancer are candidates for genetic studies when searching for a recessively inherited predisposing gene. In paper II, we studied the occurrence of cancer in first-degree relatives of breast cancer patients diagnosed with the lobular carcinoma histologic subtype compared with other histological subtypes of breast cancer. We found a hereditary pattern involving breast cancer patients with lobular carcinoma and having a father diagnosed with cancer. The association was independent of a family history of breast cancer in sisters, the mother and grandmothers. Similarly, even though prostate cancer was prominent in the fathers, the association remained after removal of fathers diagnosed with prostate cancer. In paper III, we confirmed a previously reported younger age at breast cancer diagnosis in carriers of a BRCA1 mutation of paternal origin compared with maternal origin. Additionally, we observed an older age at ovarian cancer diagnosis in carriers of a BRCA1 mutation of paternal origin compared with maternal origin. No such observations were observed for BRCA2 mutation carriers. In paper IV, we studied the occurrence of spider telangiectasias at the time of breast cancer diagnosis in relation to hormonal risk factors. We reported that the occurrence of spider telangiectasias was associated with several hormonal risk factors such as weight, parity, history of oral contraceptive use, and menopausal hormone therapy use. A better overall survival was observed in older breast cancer patients who displayed spider telangiectasias at the time of breast cancer diagnosis.
Statistical guidelines for contributors to medical journals.

Most papers published in medical journals contain analyses that have been carried out without any help from a statistician. Although nearly all medical researchers have some acquaintance with basic statistics, there is no easy way for them to acquire insight into important statistical concepts and principles. There is also little help available about how to design, analyse, and write up a whole project. Partly for these reasons much that is published in medical journals is statistically poor or even wrong.1 A high level of statistical errors has been noted in several reviews of journal articles and has caused much concern. Few journals offer even rudimentary statistical advice to contributors. It has been suggested1 2 that comprehensive statistical guidelines could help by making medical researchers more aware of important statistical principles, and by indicating what information ought to be supplied in a paper. We present below an attempt to do this. Deciding what to include in the guidelines, how much detail to give, and how to deal with topics where there is no consensus has been problematic. These guidelines should thus be seen as one view of what is important, rather than as a definitive docu? ment. We have not set out to provide a set of rules but rather to give general information and advice about important aspects of statistical design, analysis, and presentation. Those specific recommendations that we have made are mostly strong advice against certain practices. Some familiarity with statistical methods and ideas is assumed, since some knowledge of statistics is necessary before carrying out statistical analyses. For those with only a limited acquaintance with statistics, the guidelines should show that the subject is very much wider than mere significance testing and illustrate how important correct interpretation is. The lack of precise recommendations indicates that good statistical analysis re? quires common sense and judgment, as well as a repertoire of formal techniques, so that there is an art in statistics as well as in medicine. We hope that the guidelines present an uncontro versial view of the most frequently used and accepted statistical procedures. We have deliberately limited the scope of the guidelines to cover the more common statistical procedures. Readers may find that a relevant section presents information or advice that is unfamiliar or is not understood. In such circumstances, although almost all of the topics covered may be found in the more comprehensive medical statistics text? books,3 4 we strongly recommend that they should seek the advice of a statistician. The absence from the guidelines of specific references is intentional : it is better to get expert personal advice if further insight is needed. Moreover, because mistakes in design cannot later be rectified, professional advice should first be obtained when planning a research project rather than when analysing the data.
VARIABILITY AMONG FIVE DIFFERENT COMMERCIAL IGF-1 IMMUNOASSAYS IN CONDITIONS OF CHILDHOOD-ONSET GH DEFICIENCY AND GH THERAPY

Abstract IGF-1 measurement is used for screening of GH deficiency and monitoring of GH therapy in children. However, several commercial immunoassays are currently used and reference values provided by manufacturers are very different. The aim of this study was to compare commercial IGF-I assays 1) in terms of absolute values and 2) in terms of clinical interpretation of results based on IGF-I reference values in serum samples from children with GH therapy, with untreated GH deficiency and with obesity. Serum samples of 9 patients were sent frozen to 5 university hospitals using 5 different IGF-I assays. The inter-laboratory coefficient of variation (CV) was calculated for the 9 samples. For clinical interpretation, results were expressed as SD scores based on reference values provided by manufacturers (and used in these laboratories). The mean inter-laboratory CV (range) for the 9 serum samples was 25.8% (16.7-35.9%). Major variability was noted in the SD-scores between IGF-I assays for 3 tested serum samples from GH-treated patients with a difference between the lowest and highest SD score of 2.6 up to 3.2. In conclusion, there is a large variability among commercial IGF-I immunoassays, not only in terms of absolute values, but also in terms of clinical interpretation in pediatric serum samples. There is a need for IGF-I immunoassay harmonization and for the establishment of adequate reference values.
Register requirements of pipelined processors

To enable concurrent instruction execution, scientific computers generally rely on pipelining, which combines with faster system clocks to achieve greater throughput. Each concurrently executing instruction requires buffer space, usually implemented as a register, to receive its result. This paper focuses on the issue of how many registers are required to achieve optimal performance in pipelined scientific computers. Four machine models are considered: single, double, and triple issue scalar machines, and vector machines with various register lengths. A model is presented that accurately relates the register requirements for optimum performance cyclically scheduled loops with tree-dependence graphs to the degree of function unit pipelining, the instruction issue bandwidth, and code properties. A method for finding upper and lower bounds on the minimum register requirements is also presented. The result of this work is a theory for assessing register requirements that can be used to reveal fundamental differences among machines within a space of architectural and implementation design choices. Some experimental data is also provided to support the theory.
Der Zusammenhang zwischen Stimmung, Verlangen und Nikotinkonsum im Alltag von Opioidabhängigen

Hintergrund: Negative Stimmung und unwiderstehliches Verlangen sind als Auslöser des Erstkonsums einer psychotropen Substanz nach einer abstinenten Phase vielfach nachgewiesen worden. Über die Auslöser des Konsums bei Personen mit Ad-libitum-Konsum ist bisher wenig bekannt. Die vorliegende Untersuchung hatte zum Ziel, (1) den Einfluss negativer Stimmung auf die Menge des Ad-libitum-Zigarettenkonsums sowie (2) die mediierende Rolle des Verlangens in diesem Zusammenhang zu untersuchen. Patienten und Methoden: An einer opioidabhängigen Verfügbarkeitsstichprobe (N = 29) wurden mittels elektronischer Tagebücher 1 Woche lang 4-mal täglich zu individuell festgelegten Zeitpunkten Daten zu Stimmung, Verlangen und Menge des Zigarettenkonsums gewonnen und mittels «Linear Mixed Models» analysiert. Ergebnisse: Negative Stimmung 10 min vor dem Konsum sowie zum vorangegangenen Messzeitpunkt erwiesen sich als signifikante Prädiktoren der Anzahl konsumierter Zigaretten (p < 0,05). Der Einfluss des Verlangens 30 min vor dem Konsum auf die Konsummenge verfehlte knapp die statistische Signifikanz (p = 0,09). Der Vergleich des direkten Effekts negativer Stimmung auf die konsumierte Menge mit dem indirekten Effekt mediiert über das Verlangen zeigte, dass negative Stimmung ausreichte, um eine Zunahme der Konsummenge zu bewirken, ohne dass das Erleben von Verlangen eine notwendige Bedingung darstellte. Schlussfolgerung: Die Ergebnisse sprechen dafür, aktuelle negative Stimmung als einen von Verlangen unabhängigen Auslöser des Nikotinkonsums zu berücksichtigen.
An Investigation of Reading and Spelling Performance in Speech Disordered Children

The reading and spelling abilities of two groups of speech disordered children were compared with matched controls. Children with developmental verbal dyspraxia differed qualitatively as well as quantitatively from normal children and cleft palate children. A specific problem with grapheme-phoneme conversion rules is postulated for dyspraxic children and implications are discussed.
Nurses' Role in Caring for Women Experiencing Intimate Partner Violence in the Sri Lankan Context

Intimate partner violence has short- and long-term physical and mental health consequences. As the largest healthcare workforce globally, nurses are well positioned to care for abused women. However, their role in this regard has not been researched in some countries. This paper is based on a qualitative study that explored how Sri Lankan nurses perceive their role in caring for women who have experienced partner violence. Interviews with 30 nurses who worked in diverse clinical and geographical settings in Sri Lanka revealed that nurses' role involved: identifying abuse, taking care of patients' physical needs, attending to their safety, providing support and advice, and making referrals. Barriers to providing care included lack of knowledge; heavy workload; language barriers; threats to personal safety; nurses' status within the healthcare hierarchy; and lack of communication and collaboration between various stakeholder groups within the healthcare system. Nurses also identified a lack of appropriate services and support within hospitals and in the community. The findings reveal an urgent need for the healthcare system to respond to nurses' educational and training needs and help them function autonomously within multidisciplinary teams when caring for abused women. The findings also point to a need to address institutional barriers including the lack of appropriate services for abused women.