tbuckley/cabot-search huggingface dataset:
What are the four phases of clinical research trials?
Authors: P. Sedgwick
Journal: BMJ (2014)

Children with neurological and developmental disorders often experience chronic sleep disturbances. Melatonin has been commonly prescribed because of its hypnotic properties. However, trials have had conflicting results. Therefore, researchers assessed the effectiveness of melatonin in treating severe sleep problems in children with neurodevelopmental disorders. A randomised double blind placebo controlled multicentre trial study design was used. The intervention was immediate release melatonin capsules given 45 minutes before the child's bedtime for a period of 12 weeks. Treatment started with a 0.5 mg capsule, and escalated through 2 mg, 6 mg, and 12 mg, depending on the child's response to treatment.1 Participants were 146 children who had a severe sleep problem and had not responded to standardised sleep behaviour advice provided to parents four to six weeks before randomisation. Children were recruited from 19 hospitals across England and Wales. The children were randomised to melatonin (n=70) or placebo (n=76). The outcome measures included subjective (as assessed from sleep diaries completed by the parents) and objective (as recorded by actigraphy) measures of sleep. The researchers reported that children gained little additional sleep on melatonin compared with placebo. However, the children receiving melatonin fell asleep significantly more quickly and they awoke earlier. Which one of the following best describes the phase of the above clinical trial?
Species-Specific Exon Loss in Human Transcriptomes
Authors: Jinkai Wang, Zhi-xiang Lu, Collin J. Tokheim, Sara E. Miller, Yi Xing
Journal: Molecular Biology and Evolution (2014)

Changes in exon-intron structures and splicing patterns represent an important mechanism for the evolution of gene functions and species-specific regulatory networks. Although exon creation is widespread during primate and human evolution and has been studied extensively, much less is known about the scope and potential impact of human-specific exon loss events. Historically, transcriptome data and exon annotations are significantly biased toward humans over nonhuman primates. This ascertainment bias makes it challenging to discover human-specific exon loss events. We carried out a transcriptome-wide search of human-specific exon loss events, by taking advantage of RNA sequencing (RNA-seq) as a powerful and unbiased tool for exon discovery and annotation. Using RNA-seq data of humans, chimpanzees, and other primates, we reconstructed and compared transcript structures across the primate phylogeny. We discovered 33 candidate human-specific exon loss events, among which six exons passed stringent experimental filters for the complete loss of splicing activities in diverse human tissues. These events may result from human-specific deletion of genomic DNA, or small-scale sequence changes that inactivated splicing signals. The impact of human-specific exon loss events is predominantly regulatory. Three of the six events occurred in the 5' untranslated region (5'-UTR) and affected cis-regulatory elements of mRNA translation. In SLC7A6, a gene encoding an amino acid transporter, luciferase reporter assays suggested that both a human-specific exon loss event and an independent human-specific single nucleotide substitution in the 5'-UTR increased mRNA translational efficiency. Our study provides novel insights into the molecular mechanisms and evolutionary consequences of exon loss during human evolution.
Tolerance and latent cellular rejection in long-term liver transplant recipients
Authors: Terence Wong, Kayhan T. Nouri-Aria, John Devlin, Bernard Portmann, Roger Williams
Journal: Hepatology (1998)

Tolerance develops in a proportion of long-term liver transplant recipients but currently cannot be identified before an attempt at withdrawal from immunosuppression therapy. In the present study, we have examined the immunophenotypic characteristics of the cellular infiltrate in portal tracts and lobules as observed in liver biopsy specimens in relation to the outcome of subsequent withdrawal from immunosuppression therapy. Cryostat biopsy specimens from 27 long-term recipients before drug withdrawal, and from 10 patients with recent transplants who were having acute rejection, were analyzed. Immunohistochemical staining was performed for CD3 + (pan T cell), CD8 + (cytotoxic), CD4 + (helper), CD45RO + (memory), CD45RA + (naive), CD56 + (natural killer), CD68 + (macrophage), and CD8 + perforin + cells. Fewer CD8 + and CD3 + cells were present in the lobular areas of biopsy specimens from patients who were successfully withdrawn from immunosuppression therapy (n = 6) compared with biopsy specimens from patients with nontolerant grafts (n = 9; 15 vs. 23 cells/high-power field [hpf] [ P &lt; .01] and 16 vs. 26 cells/hpf [ P &lt; .03], respectively) or biopsy specimens obtained during acute rejection (15 vs. 31 cells/hpf [ P &lt; .01] and 16 vs. 32 cells/hpf [ P &lt; .01]). Cell frequencies in the biopsy specimens of nontolerant long-term patients were similar to those found with acute rejection. Immunophenotyping the lobular inflammation within long-term liver allografts assists in identifying those patients in whom drug withdrawal is likely to be unsuccessful and in whom it is postulated a form of inactive, latent cellular rejection exists.
Volume and Surface Three-Dimensional Displays of Tc-99m HMPAO Brain SPECT Imaging in a Chronic Hypnosedative Abuser
Authors: WEI-JEN SHIH, MARK HYATT
Journal: Clinical Nuclear Medicine (1993)

An alcohol- and diazepam-abusing patient underwent brain CT and SPECT imaging studies. The CT scan showed mild brain atrophy, whereas SPECT imaging using Tc-99m HMPAO showed a large lesion in the left cerebral hemisphere. The extent of lesion involvement was appreciated by three-dimensional displays. This finding was associated with a clinical presentation of hypnosedative withdrawal dellrium (disorientation, impaired memory, rambling speech with loose associations, paranola, ideation, restlessness, poor judgment), Tc-99m HMPAO SPECT may provide objective documentation of regional cerebral neurochemical alteration associated with hypnosedative abuse or hypnosedative withdrawal states, whereas surface and volume three-dimensional displays simplify and enhance brain SPECT image interpretation.
Impairment of hepatic growth hormone and glucocorticoid receptor signaling causes steatosis and hepatocellular carcinoma in mice
Authors: Kristina M. Mueller, Jan-Wilhelm Kornfeld, Katrin Friedbichler, Leander Blaas, Gerda Egger, Harald Esterbauer, Peter Hasselblatt, Michaela Schlederer, Susanne Haindl, Kay-Uwe Wagner, David Engblom, Guenter Haemmerle, Dagmar Kratky, Veronika Sexl, Lukas Kenner, Andrey V. Kozlov, Luigi Terracciano, Rudolf Zechner, Guenther Schuetz, Emilio Casanova, Andrew J. Pospisilik, Markus H. Heim, Richard Moriggl
Journal: Hepatology (2011)

Growth hormone (GH)-activated signal transducer and activator of transcription 5 (STAT5) and the glucocorticoid (GC)-responsive glucocorticoid receptor (GR) are important signal integrators in the liver during metabolic and physiologic stress. Their deregulation has been implicated in the development of metabolic liver diseases, such as steatosis and progression to fibrosis. Using liver-specific STAT5 and GR knockout mice, we addressed their role in metabolism and liver cancer onset. STAT5 single and STAT5/GR double mutants developed steatosis, but only double-mutant mice progressed to liver cancer. Mechanistically, STAT5 deficiency led to the up-regulation of prolipogenic sterol regulatory element binding protein 1 (SREBP-1) and peroxisome proliferator activated receptor gamma (PPAR-γ) signaling. Combined loss of STAT5/GR resulted in GH resistance and hypercortisolism. The combination of both induced expression of adipose tissue lipases, adipose tissue lipid mobilization, and lipid flux to the liver, thereby aggravating STAT5-dependent steatosis. The metabolic dysfunctions in STAT5/GR compound knockout animals led to the development of hepatic dysplasia at 9 months of age. At 12 months, 35% of STAT5/GR-deficient livers harbored dysplastic nodules and ˜60% hepatocellular carcinomas (HCCs). HCC development was associated with GH and insulin resistance, enhanced tumor necrosis factor alpha (TNF-α) expression, high reactive oxygen species levels, and augmented liver and DNA damage parameters. Moreover, activation of the c-Jun N-terminal kinase 1 (JNK1) and STAT3 was prominent. Conclusion: Hepatic STAT5/GR signaling is crucial for the maintenance of systemic lipid homeostasis. Impairment of both signaling cascades causes severe metabolic liver disease and promotes spontaneous hepatic tumorigenesis. (Hepatology 2011;54:1398–1409)
A meta-analysis on the clinical and angiographic outcomes of stents vs PTCA in the different coronary vessels in the benestent-1 and stress 1 and 2 trials
Authors: Sheldon Goldberg, Aida J. Azar, Ferdinand Kiemenij, Peter de Jaegere, Richard Schatz, Donald Baim, Martin Leon, Patrick W. Serruys
Journal: Journal of the American College of Cardiology (1996)
ABC of major trauma. Trauma of the spine and spinal cord--I.
Authors: A Swain, J Dove, H Baker
Journal: BMJ (1990)

Treat * Bradycardia-pulse rate <50 beats/min * Hypotension-systolic blood pressure <80 mm Hg * Inadequate urinary excretion Do not rotate the patient's neck during central venous cannulation unless cervical injury has been excluded by radiography Causes of respiratory insufficiency In tetraplegic patients * Intercostal paralysis * Partial phrenic nerve palsy-immediate -delayed * Impaired ability to expectorate * Ventilation-perfusion mismatch In paraplegic patients * Variable intercostal paralysis according to level of injury * Associated chest injuries-rib fractures, pulmonary contusion, haemopneu mothorax
Campylobacter Enteritis Associated With a Healthy Cat
Authors: Martin J. Blaser
Journal: JAMA (1982)

IN THE short time since<i>Campylobacter jejuni</i>has become recognized as a significant enteric pathogen of humans, information on the epidemiology of infection has been increasing rapidly.<sup>1</sup>Although direct contact with infected animals or consumption of contaminated water or foods of animal origin are generally suspected as being the important modes of transmission, in only the minority of cases can this be documented. Recent work has implicated contact with infected household pets as one avenue of transmission.<sup>2-4</sup>The pets involved in such cases were puppies and kittens with diarrhea who were shedding<i>C jejuni</i>. We now report a case of<i>Campylobacter</i>enteritis that occurred in association with infection in an apparently healthy adult cat. <h3>Report of a Case</h3> On Oct 15, 1980, nausea, vomiting, and severe abdominal cramps developed in a 23-year-old woman, and she began having up to five bloody bowel movements per day. On Oct 19,
311 Longer treatment duration with peginterferon alfa-2A (40KD) (Pegasys®) and ribavirin (Copegus®) in naive patients with chronic hepatitis C and detectable HCV RNA by week 4 of therapy: Preliminary results of the teravic-4 study
Authors: J SANCHEZTAPIAS, M DIAGO, P ESCARTIN, J ENRIQUEZ, R MORENO, H LAPRINCESA, M ROMEROGOMEZ, H DEVALME, R BARCENA, H YCAJAL
Journal: Hepatology (2003)
The effect of polyethylene glycol on the stability of pores in polyvinyl alcohol hydrogels during annealing
Authors: Hatice Bodugoz-Senturk, Jeeyoung Choi, Ebru Oral, Jean H. Kung, Celia E. Macias, Gavin Braithwaite, Orhun K. Muratoglu
Journal: Biomaterials (2007)
Fill-In After Reinjection of Tc-99m MAA
Authors: NAOYUKI WATANABE, NOBORU ORIUCHI, TETSUYA HIGUCHI, MASASHI YUKIHIRO, YUMI FUKUSHIMA, TSUNEO HIRANO, TOMIO INOUE, KEIGO ENDO
Journal: Clinical Nuclear Medicine (1998)

Combined pulmonary ventilation/perfusion (V/P) scintigraphy for assessing and monitoring pulmonary pathophysiology should be performed so that perfusion information exactly corresponding to ventilation can be obtained. An area of impaired V/P was shown in the affected lung of a patient with pneumothorax by combined pulmonary V/P scintigraphy. Additional combined pulmonary V/P scintigraphy following reinjection of Tc-99m MAA on a single maximal inspiration demonstrated improvement in both perfusion and ventilation The findings represent well-known pathophysiology. Hypoventilation causes reflex vasoconstriction of the pulmonary artery and when ventilation improves, so does perfusion. This suggests that a perfusion abnormality improved following pneumothorax.
Regulation of smooth muscle alpha-actin promoter by vasopressin and platelet-derived growth factor in rat aortic vascular smooth muscle cells.
Authors: V Van Putten, X Li, J Maselli, R A Nemenoff
Journal: Circulation Research (1994)

Vasoconstrictors such as arginine vasopressin (AVP) and angiotensin II (Ang II) have been shown to increase protein and mRNA levels of smooth muscle alpha-actin (SM-alpha-actin) in vascular smooth muscle cells. In the same cells, platelet-derived growth factor (PDGF) decreased SM-alpha-actin protein and mRNA. The rat SM-alpha-actin promoter that has recently been isolated contains two E-boxes and three CC(A/T)6GG (CArG) elements. To examine regulation of the SM-alpha-actin promoter, a 765-bp region of the rat SM-alpha-actin gene was ligated into chloramphenicol acetyltransferase (CAT)-containing vectors and transfected into rat aortic vascular smooth muscle cells. Stimulation of cells with either AVP or Ang II increased CAT activity 5- to 10-fold. PDGF was able to completely block the AVP-induced increase in CAT activity. To identify regions of the promoter responsible for both the AVP stimulation and PDGF inhibition of promoter activity, a series of truncation mutants were prepared and transfected into vascular smooth muscle cells. Truncation of both E-boxes and the most distal CArG element did not qualitatively alter either AVP-induced stimulation of CAT activity or PDGF inhibition. However, removal of the middle CArG element resulted in a loss of AVP stimulation. These studies indicate that the AVP-induced elevation and PDGF-induced inhibition of SM-alpha-actin levels in vascular smooth muscle cells are mediated at least in part through regulation of the SM-alpha-actin promoter. The critical region of the promoter mediating this effect involves at a minimum one of the CArG elements.
Footloose and fossil-free no more: Evolutionary psychology needs archaeology
Authors: Valerie E. Stone
Journal: Behavioral and Brain Sciences (2002)

Evolutionary theories of human cognition should refer to specific times in the primate or hominid past. Though alternative accounts of tool manufacture from Wynn's are possible (e.g., frontal lobe function), Wynn demonstrates the power of archaeology to guide cognitive theories. Many cognitive abilities evolved not in the “Pleistocene hunter-gatherer” context, but earlier, in the context of other patterns of social organization and foraging.
T Helper–Cell Phenotype Regulates Atherosclerosis in Mice Under Conditions of Mild Hypercholesterolemia
Authors: S. A. Huber, P. Sakkinen, C. David, M. K. Newell, R. P. Tracy
Journal: Circulation (2001)

Background —T cells are implicated in atherosclerosis, but little is known about the genetic control or molecular pathways, especially under conditions of mild hypercholesterolemia. Methods and Results —BALB/c mice, making a CD4+ Th2 (IL-4+) cell response, express both MHC class II antigens (IA d , IE d ) and are atherosclerosis-resistant. C57Bl/6 mice produce a CD4+ Th1 (interferon [IFN]γ+) response, express IA b but no IE, and are atherosclerosis-prone. To evaluate T helper–cell phenotype in fatty streak formation, wild-type C57Bl/6 mice (IA b +IE−) and transgenic mice, either AB o , IA b −IE−; ABEα, IA−IE k +; or Bl.Tg.Eα, IA b +IE k +, were fed a high-cholesterol diet for 16 weeks and evaluated histomorphometrically for aortic lesions. Lesion size in AB o , ABEα, and Bl.Tg.Eα strains was decreased by 54%, 79%, and 82%, respectively, compared with wild-type, correlating with decreased Th1 and increased Th2 expression and suggesting that T helper–cell phenotype is important in fatty lesion development. Decreasing Th1 cells by antibodies (α-CD4) or cytokines (IL-4) also caused ≥80% reductions in lesion size. Immunohistology revealed IFN-γ, but not IL-4, colocalized with activated macrophages. Confirming these findings in a different mouse strain, BALB/c Stat 6 knockout mice (Th2 cell–deficient) developed aortic lesions comparable to C57Bl/6 mice on the same diet. Conclusions —In mildly hypercholesterolemic C57Bl/6 mice, presence of IA b and absence of IE regulated CD4+ T helper–cell phenotype; fatty lesions were proportional to IFNγ+ Th1 cells in both C57Bl/6 and BALB/c strains. IFN-γ may participate through macrophage activation, whereas IL-4 may act to limit Th1-cell response.
How should district allocations be altered for changes in cross boundary flows?
Authors: G. Bevan
Journal: BMJ (1988)

The main principles underlying finance of health authorities in the United Kingdom are, firstly, that a health district's (or health board's) allocation ought to move towards a target that consists of an estimated fair share of resources by the district's residents and, secondly, the costs of treating non-residents.13 Where a district's current allocation exceeds its target this tends to be because its residents are using services at a level higher than their estimated fair share ,^6 and where a district's allocation is less than target this tends to be because its residents are using less than their fair share of services. Existing arrangements of accounting for services provided by one district for residents of another mean that where there is a change in the pattern of services this does not automatically result in a change in allocations. If, for example, one district provided a new service or changed the volume of services provided for another it would take two years for this change to be reflected in targets. This delay is because of the time taken to collect and process the necessary data. The decision on how to alter allocations in the light of changes in targets depends on how far districts' allocations are from their targets. If a district's allocation is close a change in its target may be fully reflected in its allocation. Where a district's allocation is a long way from its target the district's region may have decided that only gradual reductions in allocations are manageable and that the requirement for these reductions to be made would be unaffected by changes in the district's target. The NHS Management Board's Review of the Resource Allocation Working Party Formula recommended speeding up changes made in adjusting targets for changes in services.7 Districts' immediate concerns, however, are not so much over speeding up recognition in targets as the relation between changes in services and changes in allocations. This paper explains why separating changes in a district's allocation from changes in services provided for other districts has resulted in attempts to impose barriers to treatment. The implications of different systems of cross charging as a means of adjusting allocations to reflect changes in services are examined.
Three Alcohol Programs for American Indians
Authors: JAMES H. SHORE, BILLEE VON FUMETTI
Journal: American Journal of Psychiatry (1972)

The authors report on three tribally sponsored rehabilitation programs for Indian alcoholics. The programs, which represent a recent development in Indian alcoholism rehabilitation services, have matched their treatment philosophy and methods to the needs of this population. The authors stress: 1) the involvement of the Indian in planning and in operating the programs, 2) the treatment philosophy, 3) the relationship of the courts to the programs, and 4) the need for uniform standards of evaluating patients.
Obstetrics in the Winchester Hospital (1928–1947)
Authors: Sanford H. Moses
Journal: New England Journal of Medicine (1949)

IN 1938, a report on maternal mortality in the Winchester Hospital for the years 1928–1937 was published,1 with the intention of demonstrating that good obstetrics could be practiced in a small hospital. This report covers the twenty-year period 1928–1947 and includes fetal-mortality statistics for the last ten years. It is believed that the publication of statistics from this hospital and discussion of the problems and results will be of value to those who practice in similar institutions. Most of the available statistics come either from large maternity hospitals or from city, state or national areas. The figures presented below show . . .
Gender Verification in the Olympics
Authors: Joe Leigh Simpson
Journal: JAMA (2000)

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Liberal Democrats will abolish health quangos that cost NHS 1.2bn
Authors: D. Cohen
Journal: BMJ (2010)

The National Patient Safety Agency, National Treatment Agency, and the NHS Litigation Authority would all be abolished under Liberal Democrat proposals to reduce bureaucracy in the NHS.

In their blueprint for the NHS (not the official manifesto), Norman Lamb, Liberal Democrat health spokesman, described a “complex web of quangos and regulators” costing the NHS £1.2bn (€1.4bn; $1.9bn) per year.

Also on the Liberal Democrats’ list for the axe are primary care trusts, which would be replaced by directly elected health boards that have a legal duty to provide value for money. It is this shift from central “bureaucratic control” and emphasis on NHS finances in the run up to the election that has marked the Liberal Democrats out from the other parties.

Jonathan Nicholls, research director of health and the NHS for pollsters Ipsos MORI, said that NHS finances don’t seem to be part of the debate. “Even flat funding for the NHS over the next three years equates to a 15-20% cut,” he said.

But speaking at the King’s Fund this week, Mr Lamb described the four main planks of …