tbuckley/cabot-search huggingface dataset:
Breaking the waves: improved detection of copy number variation from microarray-based comparative genomic hybridization
Authors: John C Marioni, Natalie P Thorne, Armand Valsesia, Tomas Fitzgerald, Richard Redon, Heike Fiegler, T Daniel Andrews, Barbara E Stranger, Andrew G Lynch, Emmanouil T Dermitzakis, Nigel P Carter, Simon Tavaré, Matthew E Hurles
Journal: Genome biology (2007)

Large-scale high throughput studies using microarray technology have established that copy number variation (CNV) throughout the genome is more frequent than previously thought. Such variation is known to play an important role in the presence and development of phenotypes such as HIV-1 infection and Alzheimer's disease. However, methods for analyzing the complex data produced and identifying regions of CNV are still being refined. We describe the presence of a genome-wide technical artifact, spatial autocorrelation or 'wave', which occurs in a large dataset used to determine the location of CNV across the genome. By removing this artifact we are able to obtain both a more biologically meaningful clustering of the data and an increase in the number of CNVs identified by current calling methods without a major increase in the number of false positives detected. Moreover, removing this artifact is critical for the development of a novel model-based CNV calling algorithm - CNVmix - that uses cross-sample information to identify regions of the genome where CNVs occur. For regions of CNV that are identified by both CNVmix and current methods, we demonstrate that CNVmix is better able to categorize samples into groups that represent copy number gains or losses. Removing artifactual 'waves' (which appear to be a general feature of array comparative genomic hybridization (aCGH) datasets) and using cross-sample information when identifying CNVs enables more biological information to be extracted from aCGH experiments designed to investigate copy number variation in normal individuals.
Methisazone for Prophylaxis Against Chickenpox
Authors: Dwayne Reed
Journal: JAMA (1966)

THE ORIGINAL WORK of Thompson et al<sup>1</sup>in 1953 showed the antiviral activity of isatin β-thiosemicarbazone in mice infected with vaccinia virus. A later derivative, methisazone (Marboran), was found to possess marked antiviral activity in mice infected with smallpox virus.<sup>2</sup>The definitive work by Bauer et al<sup>3</sup>in 1963 showed the antiviral activity of methisazone in human contacts of smallpox cases. The evidence of this latter study stimulated investigations of the use of this drug as a prophylaxis for other viral infections. This communication is a report of the use of methisazone for prophylaxis against chickenpox in a small clinical trial. <h3>Methods</h3> In collaboration with the Alaska Native Area Office, we were authorized by the Food and Drug Administration to conduct field trials of methisazone at the Alaska Native Medical Center, Anchorage. Over half of the native children hospitalized in the 120-bed pediatric service of this hospital
More on Privacy and Birth Control
Authors: William J. Curran
Journal: New England Journal of Medicine (1965)

A PREVIOUS column1 just a few months ago commented on the United States Supreme Court's landmark decision2 striking down the Connecticut law that made it illegal for married couples to use contraceptive devices to control birth. In doing so, the Supreme Court raised "the right of privacy" in intimate marital relations to a constitutionally protected status.Since the publication of that column, there have been 2 public utterances on these issues that deserve examination for the readers of the Journal. The first is the statement of Mr. William B. Ball, attorney for the Pennsylvania Catholic Conference, before the United . . .
Limb congestion and sympathoexcitation during exercise. Implications for congestive heart failure.
Authors: J McClain, C Hardy, B Enders, M Smith, L Sinoway
Journal: Journal of Clinical Investigation (1993)

During static exercise, heart failure (HF) subjects activate the sympathetic nervous system differently than normal controls. HF causes metaboreceptor desensitization with either enhanced mechanoreceptor activity or central command. In this report, we examined whether increased muscle interstitial pressure, as seen in HF, augments other neural systems. We measured muscle sympathetic nerve activity (MSNA; peroneal nerve) in 10 normals during static exercise (40% maximal voluntary grip) and posthandgrip circulatory arrest (PHG-CA). This was repeated after venous congestion (VC; cuff inflation to 90 mmHg). VC increased forearm volume (plethysmography) by 4.7%. MSNA responses to exercise were greater after VC (150.5 +/- 41.8 vs. 317.3 +/- 69.9 arbitrary units; P < 0.01). However, MSNA responses during PHG-CA were not affected by VC, and 31P nuclear magnetic resonance (n = 5) demonstrated no effect of VC on pH or H2PO4-. Similar effects of VC on MSNA were noted after ischemic exercise (n = 7), excluding flow alterations as the explantation. VC probably sensitized mechanically sensitive afferents since MSNA during involuntary biceps contractions increased after VC (n = 6), and skin sympathetic nerve responses during handgrip, an index of central command, were not increased by VC (n = 6).
Massive Pulmonary Embolism in a High School Wrestler
Authors: Philip H. Croyle
Journal: JAMA (1979)

DEEP-vein thrombosis is an unusual entity in teenage boys, and pulmonary embolism is rarer still. We report a case of a young athlete in whom both occurred and discuss a possible association with the precompetition  loss that is commonly practiced in wrestling.  Report of a Case  A 16-year-old high school wrestler weighing 49.5 kg had a flu-like syndrome that included fever, nausea, weakness, and myalgias two days before a match. He lost 3.5 kg to make weight for the match and was defeated by an opponent he had handily beaten before. He was dyspneic for 30 minutes after his fall. Four days later he competed again, this time losing 2.5 kg by sweating and restricting fluid intake. He became exhausted in the second period and was pinned; cyanosis was noted, and oxygen was administered. The next day his physician heard a heart murmur, and the patient was transferred to
Arterial gene transfer to rabbit endothelial and smooth muscle cells using percutaneous delivery of an adenoviral vector.
Authors: P G Steg, L J Feldman, J Y Scoazec, O Tahlil, J J Barry, S Boulechfar, T Ragot, J M Isner, M Perricaudet
Journal: Circulation (1994)

BACKGROUND Previous investigations in live animals convincingly established that arterial gene transfer, while feasible, was compromised by a low transfection efficiency. More recent studies have shown that transfection efficiency may be substantially augmented by the use of recombinant adenoviral vectors. Most in vivo transfections reported to date, however, have used direct (operative) administration of the adenoviral vector. Clinical applications of arterial gene transfer (such as prevention of restenosis), however, would require local percutaneous delivery of the transgene. The present study was designed to extend in vivo intraoperative findings to percutaneous delivery system and to assess whether gene transfer remains site specific. METHODS AND RESULTS A recombinant, replication-defective adenovirus modified to include an expression cassette for nucleus-targeted beta-galactosidase was introduced into rabbit iliac arteries in vivo using either a double-balloon catheter (DBC, n = 27) or a hydrogel-coated balloon catheter (HBC, n = 27). Contralateral arteries-normal, endothelium-denuded, or sham-transfected with a control adenoviral vector-served as controls. beta-Galactosidase expression was assessed by X-Gal staining. Cell-transduction efficiency was measured by morphometric analysis. Polymerase chain reaction (PCR) and histochemistry were used to detect the presence and/or expression of viral DNA in remote organs. Transgene expression was detected in all cases (46 of 46) between 3 and 14 days after transfection but was in no case detectable 28 days after transfection. In the DBC group, transgene expression was limited to endothelial cells when the endothelium was left intact and to rare medial cells (&lt; 2.2%) when it had been removed. In contrast, HBC delivery resulted in transduction of up to 9.6% of medial smooth muscle cells (P = .0001). Optimized PCR and histochemistry failed to detect evidence of extra-arterial transfection except in a small number of cells (between 1 in 3 x 10(2) and 1 in 3 x 10(5) cells) in the livers of 2 animals in the DBC group. CONCLUSIONS (1) Efficient, adenovirus-mediated, arterial gene transfer to endothelial and/or smooth muscle cells is feasible by percutaneous, clinically applicable techniques. (2) Consistent transfection of medial smooth muscle cells may be achieved when the endothelial layer is abraded. (3) Medial transfection is more efficient when an HBC, rather than a DBC, is used. (4) Percutaneous delivery of the adenoviral vector via HBC results in site-specific arterial gene transfer. Very-low-level extra-arterial transfection may occur, however, when the DBC is used.
Urban slums and primary health care.
Authors: P Garner, I Thaver
Journal: BMJ (1993)

in 1989.On the positive side, fluoridation continues to provide substantial benefits for the dental health of six million people, many of them living in the west midlands and the north east of England.4The arguments for extending fluoridation are not as overwhelming as they were in 1956.The prevalence of dental caries has fallen in both fluoridated and non-fluoridated districts,5 and the costs of fluoridation plant designed to meet modem operating standards are considerable.6It is sensible therefore that the health departments should give priority for new schemes to areas such as the north west of England7 and the west of Scotland where the prevalence of dental caries remains high and where large water treatment works allow for economies of scale.The Water (Fluoridation) Act 1985 placed the responsibility for decisions on water fluoridation with district health authorities, who are required to consult locally before making a formal request to the water undertaker.It was assumed, incorrectly as we now know, that water undertakers would concern themselves mainly with the technical feasibility of the proposal.8Experience in the North Western Region, where 18 district health authorities completed consultation in 1988, and more recently in Strathclyde, Yorkshire, Wessex, and Northern Ireland, clearly shows that health authorities can obtain substantial public and professional support for fluoridation, even though opinion among local authorities remains divided.It is also clear that the cooperation of the water companies cannot be assumed.For example, the chairman of Welsh Water stated recently that, in spite of assurances from the Drinking Water Inspec- torate concerning the safety of fluoridation plant designed according to the Department of Environment's code of practice,6 his company would not continue fluoridation on Anglesey or extend fluoridation into the rest of Wales unless required to do so by the secretary of state.While ministers quite correctly point out that the act requires local consulta- tion, it was surely not the intention of parliament that water undertakers should have such an absolute veto.The recent fundamental review of dental remuneration by Sir Kenneth Bloomfield called for "a more robust approach" to fluoridation "which would not allow for indefinite pro- crastination in adopting measures judged by the competent health authorities to be both beneficial and cost effective."9The secretary of state should now require water undertakers to implement fluoridation schemes when they are requested to do so by health authorities, subject to assurances that the proposed schemes are technically feasible and economically sensible.
Urinary Lipid and the Maltese Cross
Authors: James B. Hudson, Allen J. Dennis, Robert E. Gerhardt
Journal: New England Journal of Medicine (1978)

LIPID droplets that may be seen in the urine, particularly from patients with glomerular disease and heavy proteinuria, can act as liquid crystals and show a distinctive form on polarizing microscopy that for years has been referred to as a Maltese cross — perhaps erroneously.Although the anisotropic properties of lipid droplets from human tissue had been described earlier, Kaiserling and Orgler reported this finding in urine in 1902.1 Munk, who established the relation of these urinary lipid droplets to the nephrotic syndrome, described the characteristic figure seen with crossed Nicol prisms as an Achsenkreuz or Axenkreuz 2 (which indicates co-ordinate . . .
The Aims of Child Rearing
Authors: Harry Bakwin
Journal: New England Journal of Medicine (1953)

THE pediatrician is a newcomer in the field of mental health. There is good reason for this. Until recent years he was occupied with more urgent matters. Infants were dying in large numbers — the infant death rate in America in 1900 was more than four times what it is now. Mothers — and doctors too — were more concerned about a loose bowel movement than a frustration. Breast feeding was regarded as part of a mother's job. In addition, breast milk meant protection, to some degree, against the very serious summer diarrhea. No one thought especially about the relation . . .
Dual Isotope Scanning with Gallium-67 Citrate and Technetium-99m Radiopharmaceuticals
Authors: ROBERT D. KARL, MICHAEL F. HARTSHORNE, MICHAEL A. CAWTHON, JOHN M. BAUMAN, WILLIAM H. HOWARD, STEPHEN R. BUNKER
Journal: Clinical Nuclear Medicine (1985)

The interpretation of Ga-67 scans is limited by the complex anatomic and physiologic distribution of Ga-67 and by the low resolution possible with this isotope. The use of a second isotope Tc-99m, tagged to an appropriate pharmaceutical allows the identification of anatomic landmarks. Computer acquisition of both the Ga-67 and Tc-99m images allows for subtraction of the Tc-99m images from the Ga-67 images and leads to precise localization of abnormal Ga-67 accumulations. Only a small percentage of the counts in the Tc-99m window are due to Ga-67 scatter and do not degrade the Tc-99m images. Cases illustrating the value of the dual-isotope technique are presented.
Marginal analysis in practice: an alternative to needs assessment for contracting health care
Authors: D Cohen
Journal: BMJ (1994)

Prioritising health care services on the basis of total needs can lead to inefficient use of resources. A better option is to determine priorities by marginal analysis, which examines the effects of altering the existing balance of expenditure between health care programmes. Resources to support investment are released from disinvestments-that is, the strategy is resource neutral. Thus an increase in total health benefits is achieved independent of any gains that may result from increased spending on health. In 1989 the Welsh Health Planning Forum identified 10 health gain areas, outlining within each one where further investment was likely to produce health gains and where disinvestment might be considered. All Welsh districts then attempted, with varying degrees of success, to produce a resource neutral strategy. Mid Glamorgan further explored the possibility of using marginal analysis in producing its strategy and influencing its policy for contracting. Working groups for most health gain areas each proposed 10 programmes for investment and a further 10 for disinvestment, which were then evaluated by a core evaluation team. In the case of maternal and child health the team dropped 10 of the 20 proposals. The remainder were considered by the health authority, which dropped a further proposal. Nine of the original 20 proposals thus formally became policy for 1995.
Cysteamine enhances the procoagulant activity of Factor VIII-East Hartford, a dysfunctional protein due to a light chain thrombin cleavage site mutation (arginine-1689 to cysteine).
Authors: A M Aly, M Arai, L W Hoyer
Journal: Journal of Clinical Investigation (1992)

We have recently identified the molecular defect responsible for cross-reacting material-positive hemophilia A in two unrelated patients in which the substitution of cysteine for arginine-1689 (Factor VIII-East Hartford[FVIII-EH]) abolishes a critical Factor VIII light chain thrombin cleavage site. As other mutant proteins with a cysteine for arginine substitution have been modified in the presence of cysteamine, we have determined the effect of this and other reducing agents on FVIII-EH function. Cysteamine concentrations between 0.1 and 10 mM caused dose- and time-dependent increases in FVIII-EH VIII:C activity, as much as 14-fold (to 35 and 62 U/dl for the two patients tested). Comparable data were obtained in a standard one-stage VIII:C coagulation assay and in a chromogenic substrate assay measuring Factor Xa generation. Thrombin cleavage of the FVIII-EH light chain in the presence of cysteamine was documented by immunoadsorption and analysis. Cystamine and cysteamine-S-phosphate, similar compounds that do not possess a free thiol group, had no effect. Cysteamine augmentation of FVIII-EH VIII:C was abolished by the simultaneous addition of N-ethyl maleimide or iodoacetamide, but these sulfhydryl blocking agents did not prevent the VIII:C increase and light chain cleavage by thrombin if the plasma samples were dialyzed to remove the inhibitors before adding the cysteamine. However, incubation with DTT before iodoacetamide prevented the cysteamine effect after dialysis. These data suggest that when isolated from patient plasma, FVIII-EH cysteine-1689 is present in a disulfide bond. This bond is cleaved by cysteamine to form a new mixed disulfide, a pseudolysine that restores a thrombin cleavage site that is essential for procoagulant function.
FDA Regulation Dermatology Panel
Authors: Gordon C. Sauer
Journal: JAMA (1971)

<h3>To the Editor.—</h3> Several aspects of the SPECIAL COMMUNICATION on "Drug Combinations: A Critique of Proposed New Federal Regulations," by F. Gilbert McMahon, MD, deserve comment, especially the statement at the end of the article (<b>216</b>:1008, 1971) that regulations involving clinicians ought to be made with the advice of clinicians and not simply with that of armchair MDs on blue-ribbon committees. As a member of one of the three dermatology Panels of the Food and Drug Administration—Drug Efficacy Study, not only do I take exception to his statement about "armchair" MDs, but I really wonder where he got the information. The inference that private practitioners were not involved in the judgements regarding these hundreds of drugs studied by the Drug Efficacy Study would be refuted by a careful study of the committee members and their positions. The accurate way to determine the exact amount of time that each one
FRONTAL LOBOTOMY 1936-1956 A FOLLOW-UP STUDY OF 3000 PATIENTS FROM ONE TO TWENTY YEARS
Authors: WALTER FREEMAN
Journal: American Journal of Psychiatry (1957)

Three thousand lobotomy patients have been compared in 3 different categories: (1) Prefrontal lobotomy versus transorbital lobotomy; (2) private patients versus state hospital patients; (3) according to personality reaction type, schizophrenic, affective and psychoneurotic. Follow-up studies reveal that following prefrontal lobotomy some 70% of schizophrenics, 80% of affectives, and 90% of psychoneurotics are functioning outside of the hospital in the 5-to 10-year period. This figure is twice as high in private patients as it is in state hospital patients. Transorbital lobotomy is safer, more effective (with the exception of the hallucinated schizophrenic patients), and far more applicable to the problem of the state hospital, than is prefrontal lobotomy. [see table 2 in source pdf] Multiple operations have been performed in about 1 patient in 10, with eventual satisfactory results in a third of them. When it is considered that this fraction amounts to 100 patients out of the hospital, this figure acquires significance. Hospitals that select patients for operation with a view to release, and that encourage the relatives of patients to participate actively in the management of convalescence, enjoy a much higher percentage of released patients than do those that employ lobotomy more for the control of disturbed behavior.
Assessing Nutritional Status
Authors: PAUL JAY FRIEDMAN
Journal: Annals of Internal Medicine (1985)

Letters and Corrections1 February 1985Assessing Nutritional StatusPAUL JAY FRIEDMAN, M.D.PAUL JAY FRIEDMAN, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-102-2-278_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: I disagree with the way Kotler and associates (1) interpreted their nutritional measures. The table they used as a standard for midarm circumference (2) was derived in large part from the dubious surveys of the American garment industry before 1941 (3). The resultant standards have been replaced by the percentiles from the large Health and Nutrition Examination (HANES-I) survey, which are stratified by age and sex (4). Kotler and associates incorrectly stated that the standards they used were age-specific; in fact, only one value is given for adults of each sex. Kotler and associates assigned percentiles for...References1. KOTLERGAETZLANGEKLEINHOLT DHMEP. Enteropathy associated with acquired immunodeficiency syndrome. Ann Intern Med. 1984;101:421-8. LinkGoogle Scholar2. JELLIFFE D. Assessment of the nutritional status of the community. WHO Monogr Ser. 1966;53:3-271. Google Scholar3. O'BRIENSHELTON RW. Women's Measurements for Garment and Pattern Construction. Washington D.C.: United States Department of Agriculture; 1941 miscellaneous publication no. 454. Google Scholar4. FRISANCHO A. New norms of upper limb fat and muscle areas for assessment of nutritional status. Am J Clin Nutr. 1981;34:2540-5. CrossrefMedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Waikato Hospital Hamilton New Zealand PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited ByLIVE LONGER, BUT HOW? NUTRITION AND AGING 1 February 1985Volume 102, Issue 2Page: 278-278KeywordsHealth surveysNutrition Issue Published: 1 February 1985 PDF DownloadLoading ...