tbuckley/cabot-search huggingface dataset:
Polysaccharide Conjugate Vaccine against Pneumococcal Pneumonia in Adults
Authors: Marc J.M. Bonten, Susanne M. Huijts, Marieke Bolkenbaas, Chris Webber, Scott Patterson, Samantha Gault, Cornelis H. van Werkhoven, Anna M.M. van Deursen, Elisabeth A.M. Sanders, Theo J.M. Verheij, Michael Patton, Anne McDonough, Anita Moradoghli-Haftvani, Helen Smith, Tracey Mellelieu, Michael W. Pride, Graham Crowther, Beate Schmoele-Thoma, Daniel A. Scott, Kathrin U. Jansen, Rita Lobatto, Bas Oosterman, Nils Visser, Esther Caspers, Andre Smorenburg, Emilio A. Emini, William C. Gruber, Diederick E. Grobbee
Journal: New England Journal of Medicine (2015)

Pneumococcal polysaccharide conjugate vaccines prevent pneumococcal disease in infants, but their efficacy against pneumococcal community-acquired pneumonia in adults 65 years of age or older is unknown.In a randomized, double-blind, placebo-controlled trial involving 84,496 adults 65 years of age or older, we evaluated the efficacy of 13-valent polysaccharide conjugate vaccine (PCV13) in preventing first episodes of vaccine-type strains of pneumococcal community-acquired pneumonia, nonbacteremic and noninvasive pneumococcal community-acquired pneumonia, and invasive pneumococcal disease. Standard laboratory methods and a serotype-specific urinary antigen detection assay were used to identify community-acquired pneumonia and invasive pneumococcal disease.In the per-protocol analysis of first episodes of infections due to vaccine-type strains, community-acquired pneumonia occurred in 49 persons in the PCV13 group and 90 persons in the placebo group (vaccine efficacy, 45.6%; 95.2% confidence interval [CI], 21.8 to 62.5), nonbacteremic and noninvasive community-acquired pneumonia occurred in 33 persons in the PCV13 group and 60 persons in the placebo group (vaccine efficacy, 45.0%; 95.2% CI, 14.2 to 65.3), and invasive pneumococcal disease occurred in 7 persons in the PCV13 group and 28 persons in the placebo group (vaccine efficacy, 75.0%; 95% CI, 41.4 to 90.8). Efficacy persisted throughout the trial (mean follow-up, 3.97 years). In the modified intention-to-treat analysis, similar efficacy was observed (vaccine efficacy, 37.7%, 41.1%, and 75.8%, respectively), and community-acquired pneumonia occurred in 747 persons in the PCV13 group and 787 persons in placebo group (vaccine efficacy, 5.1%; 95% CI, -5.1 to 14.2). Numbers of serious adverse events and deaths were similar in the two groups, but there were more local reactions in the PCV13 group.Among older adults, PCV13 was effective in preventing vaccine-type pneumococcal, bacteremic, and nonbacteremic community-acquired pneumonia and vaccine-type invasive pneumococcal disease but not in preventing community-acquired pneumonia from any cause. (Funded by Pfizer; CAPITA ClinicalTrials.gov number NCT00744263.).
Australians must have their children fully immunised to receive benefit
Authors: M. Sweet
Journal: BMJ (2011)

Parents who do not have their children fully immunised by the age of 5 years stand to lose AUD$2100 (£1375; €1600; $2150) in benefits under reforms announced by the Australian government.

Under current arrangements, families who meet immunisation requirements when their child turns 2 and 5 receive a Maternity Immunisation Allowance of $129 per instalment.

From next July, this allowance will no longer be paid, and families instead must have their children fully immunised to receive an existing tax benefit supplement, which is not paid to the highest income earners.

The payment, worth $726 per child each year, will be paid once a child is fully immunised at 1, 2, and 5 years of age. Meningococcal C, pneumococcal, and varicella will be added to the immunisations needed to qualify for the payment.

Although parents can …
Twenty years of childhood coeliac disease in The Netherlands: a rapidly increasing incidence?
Authors: E K George, M L Mearin, H C Franken, R H Houwen, R A Hirasing, J P Vandenbroucke
Journal: Gut (1997)

BACKGROUND: The incidence of coeliac disease varies internationally. AIMS: To assess the incidence of childhood coeliac disease in The Netherlands and to study the clinical features and the presence of associated disorders. SUBJECTS: Identified cases of childhood coeliac disease in The Netherlands in 1993-4 by means of the Dutch Paediatric Surveillance Unit. METHODS: Inclusion criteria were born in The Netherlands, diagnosed with at least one biopsy of the small bowel in 1993-4 and age at diagnosis 0-14 years. The data were cross checked by the Dutch Network and National Database of Pathology and compared with data from a previous study on childhood coeliac disease, 1975-90. RESULTS: A total of 193 coeliac patients were identified by means of the Surveillance Unit, another 20 through the National Database of Pathology. The mean crude incidence rate of diagnosed childhood coeliac disease was 0.54/1000 live births, which is in the range of rates found in other western European countries and significantly higher than the mean crude incidence rate of 0.18/1000 live births found in The Netherlands in 1975-90. The clinical presentation was classic: chronic diarrhoea, abdominal distension, and growth failure. Associated disorders were present in 11.7% of the cases. CONCLUSIONS: The incidence of diagnosed childhood coeliac disease in The Netherlands seems to have increased significantly during the past few years. In a period of 20 years no significant changes could be found in the clinical picture at preentation of coeliac disease in Dutch children.
Increased Prevalence of Celiac Disease Among Pediatric Patients With Irritable Bowel Syndrome
Authors: Fernanda Cristofori, Claudia Fontana, Annamaria Magistà, Teresa Capriati, Flavia Indrio, Stefania Castellaneta, Luciano Cavallo, Ruggiero Francavilla
Journal: JAMA Pediatrics (2014)

<h3>Importance</h3> Recurrent abdominal pain is a prevalent health issue in childhood. Clinical criteria (ie, the Rome criteria) have been established to aid diagnosis. Studies of adults have shown an increased prevalence of celiac disease among patients with irritable bowel syndrome (IBS); few data are available with regard to children. <h3>Objective</h3> To assess the prevalence of celiac disease among children with abdominal pain–related functional gastrointestinal disorders classified according to the Rome criteria. <h3>Design, Setting, Participants</h3> Six-year (2006-2012) prospective cohort study conducted in a tertiary referral center for the diagnosis and follow-up of gastrointestinal disorders in southern Italy (ie, Bari, Italy). A total of 992 children (42.8% male; median age, 6.8 years) consecutively referred for recurrent abdominal pain by their primary care physicians without previous investigation were evaluated. <h3>Exposure</h3> Patients were classified according to Rome III criteria as having IBS, functional dyspepsia, functional abdominal pain, or abdominal migraine. <h3>Main Outcomes and Measures</h3> Prevalence of celiac disease in each category of abdominal pain–related functional gastrointestinal disorder. Concentrations of IgA, IgA antitissue transglutaminase, and endomysial antibodies were measured, and a duodenal biopsy was performed in case of antibody positivity. <h3>Results</h3> A total of 992 children were evaluated: 270 were classified as having IBS, 201 as having functional dyspepsia, and 311 as having functional abdominal pain, and 210 children were excluded from the study because they had an organic disorder or some other functional gastrointestinal disorder (not related to abdominal pain). Serologic testing was performed for all 782 children included in the study, and 15 patients tested positive for celiac disease (12 of 270 patients with IBS [4.4%], 2 of 201 patients with functional dyspepsia [1%], and 1 of 311 patients with functional abdominal pain [0.3%]). Children presenting with IBS have a 4 times higher risk of having celiac disease than children without IBS (odds ratio, 4.19 [95% CI, 2.03-8.49];<i>P</i> &lt; .001). <h3>Conclusions and Relevance</h3> The prevalence of celiac disease among children with IBS is 4 times higher than among the general pediatric population. Rome III classification of abdominal pain–related functional gastrointestinal disorders might help to select children who deserve screening for celiac disease.
Cytokines in lupus nephritis, levels of IL-17 and IL-23 in association to histopathology and response to treatment
Authors: A Zickert, P Amoudruz, J Rönnelid, V Malmström, I Gunnarsson
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Background and objectives</h3> The pathogenesis for lupus nephritis (LN) involves multiple components of the immune system. Recent studies indicate an important role for the T cell subset Th-17, and the associated cytokines IL-17 and IL-23, in LN. Increased knowledge of cytokines in LN may contribute to further understanding of the pathogenesis, identification of new biomarkers and to development of new treatment strategies. Here the authors aimed to investigate cytokines, previously indicated in LN, in association to histopathological findings and response to therapy. <h3>Methods</h3> Fifty-two patients with active lupus nephritis were included. Renal biopsies were performed at baseline and after 6 months of standard induction treatment. Clinical and laboratory data were collected at baseline and at repeated biopsies and serum levels of tumour necrosis factor α (TNFα), IFN-γ, IL-2, IL-4, IL-6, IL-10, IL-6R, IL-17, IL-23 and TGFβ were analysed at both occasions. Biopsies were evaluated regarding WHO-classification and renal disease activity was estimated using the BILAG index. An improvement of at least two grades in renal BILAG was regarded complete response (CR), whereas 1 grade as partial response (PR). Serum samples from 13 healthy volunteers were used as controls. <h3>Results</h3> Baseline biopsies showed WHO-class III-IV (n=44) and V (n=8) and all patients had high renal disease activity (BILAG A/B). Follow-up biopsies showed WHO I-II (n=19), III-IV (n=19) or V (n=14). Twenty-two patients were regarded CR, 20 PR and 10 non-responders. At baseline, levels of IL-6, IL-10, IFNγ, IL-17, IL-23 and IL-6R were significantly higher in patients versus controls and TGFβ was significantly lower (p&lt;0.05 for all). Levels of IL-17 at baseline were significantly higher in patients with a persisting active nephritis at follow-up (WHO III, IV or V) versus those with a good histopathological response (WHO I or II) (p&lt;0.03). The highest levels of IL-17 were found in WHO class V. BILAG non-responders had significantly higher levels of IL-23 at follow-up versus CR and PR (p&lt;0.05), most pronounced among non-responder patients with WHO class V (p&lt;0.02). <h3>Conclusions</h3> High baseline IL-17 predicted an unfavorable histopathological response, suggesting that patients with high levels of IL-17 may represent a subgroup with more severe disease. BILAG non-responders had high levels of IL-23. This study indicates a role for the IL-23/IL-17 axis in LN regarding response to treatment and suggests that these cytokines may be used as biomarkers and may be targets for future therapies.
P394Investigation of the effect of troponin I phosphorylation on troponin C by molecular dynamics simulations
Authors: M Papadaki, I Gould, A Messer, S Marston
Journal: Cardiovascular Research (2014)

The Ca2+ switch of cardiac muscle is modulated by phosphorylation of Ser 22 and 23 in the cardiac specific N-terminus of Troponin I (TnI) by PKA in response to beta-adrenergic stimulation. It has proposed that the unphosphorylated N terminal peptide of TnI binds to the N terminal lobe of troponin C (TnC) and that the interaction enhances Ca2+ sensitivity. The interaction is abolished by PKA phosphorylation of Ser 22 and 23 reducing Ca2+-sensitivity and increasing the rate of Ca2+ dissociation. The full structure of cardiac troponin is not known since Takeda's 2003 X-ray structure of the core of cardiac troponin (Nature 424, 35) does not contain several important mobile peptides including the N-terminal 31 amino acids. Here we show the structural changes of troponin that occur upon phosphorylation using molecular dynamics. We have applied molecular dynamics simulations to an expanded model of the Takeda et al. structure (385 amino acids) that includes the first 31 residues of TnI that we have added in as a linear chain above the TnC N-terminal lobe according to the model of Howarth et al., (J Mol Biol 373, 709). All simulations have been performed for at least a quarter of a microsecond (with some simulations up to 750 ns) with the AMBER GPU MD package in an isobaric-isothermal, NPT, ensemble. In the Ca2+-bound unphosphorylated state there is a persistent interaction between Ser 22 and 23 of TnI and Ser 69 and Thr 71 in the Ca2+-binding loop of TnC and the Ca2+ appears strongly coordinated and immobile. The extreme N-terminal 1 to 16 amino acids of TnI are very mobile apart from the two Serines, Lys 20 is the only residue making a persistent interaction with TnC. In the absence of Ca2+ the N-terminal 30 amino acids of cTnI are fully mobile and not interacting with TnC. In addition there are long-range differences in TnI structure due to phosphorylation or removal of Ca2+, centered on the TnI helix II that is partly unwound. Phosphorylation leads to restructuring after 50 ns with the loss of the TnI Ser 22 and 23 contacts with TnC and a re-orientation of the TnC N-terminal lobe relative to the rest of troponin. Ca2+ becomes more exposed to solvent. Between 100 and 150 ns the Ca2+ dissociates and re-associates, suggesting weaker binding, which is being investigated in silico. The simulation is consistent with the hypothesis of a unique TnI Ser 22/23-TnC Ca2+-binding loop II interaction that is destabilized by phosphorylation, thus weakening the affinity of the regulatory Ca2+.
Oral contraceptives and breast cancer: a national study.
Authors: C Paul, D C Skegg, G F Spears, J M Kaldor
Journal: BMJ (1986)

In a population based case-control study 433 New Zealand women aged 25-54 with newly diagnosed breast cancer were compared with 897 women selected at random from the electoral rolls. The relative risk of breast cancer in women who had ever used oral contraceptives was 0.94 (95% confidence interval 0.70 to 1.25). The relative risk in women aged 25-34 at diagnosis was estimated to be 2.2 (95% confidence interval 0.47 to 9.9) and in older women less than 1. Analyses of risk by duration of use of oral contraceptives, age at first use, and time since first use showed no adverse effect of the pill. In particular, there was no increased risk in women who had used oral contraceptives before the age of 25 or before their first pregnancy, even for prolonged periods. Given the high prevalence of use in New Zealand, this study provides strong evidence against the hypothesis that use of oral contraceptives at young ages increases the risk of breast cancer.
The effect of sleep fragmentation on daytime function.
Authors: S E Martin, H M Engleman, I J Deary, N J Douglas
Journal: American Journal of Respiratory and Critical Care Medicine (1996)

Patients with the sleep apnea/hypopnea syndrome suffer from impaired daytime function. This has been attributed to both sleep fragmentation and hypoxemia. To help understand which is casual, we studied the effects of sleep fragmentation alone on daytime function. Sixteen normal subjects were studied on two pairs of two nights. The first night of each pair was for acclimatization, and on the second the subject either slept undisturbed or had sleep fragmented with sound pulses every 2 min. Sound volume and duration was titrated to cause a return to theta or alpha rhythm on the EEG for at least 3 s. Study nights were followed by daytime testing of psychometric function and mood and by a multiple sleep latency test (MSLT) and a maintenance of wakefulness test (MWT). Total sleep time did not differ between study nights (400 +/- 20 SD min undisturbed, 396 +/- 24 min fragmented; p = 0.6). Fragmentation decreased sleep latency on both the MSLT (11 +/- 3, 7 +/- 2 min; p = 0.001) and the MWT (34 +/- 8, 24 +/- 10 min; p<0.001). Energetic arousal (22 +/- 4, 19 +/- 4; p = 0.005) and hedonic tone (29 +/- 4, 27 +/- 4; p = 0.05) decreased after fragmentation. Fragmentation impaired daytime function adjudged by the Trailmaking B (p = 0.05) and PASAT 4-s tests (p<0.03). One night of sleep fragmentation makes normal subjects sleepier during the day, impairs their subjective assessment of mood, and decreases mental flexibility and sustained attention.
A NEW AND PHYSIOLOGIC EXPLANATION OF A COMMON PSYCHOLOGIC PHENOMENON.
Authors: F. PARK LEWIS
Journal: JAMA (1906)

On first viewing an unfamiliar scene many people have, doubtless, experienced the curious sensation of having seen it before. This may have been obviously impossible. It may have been in a part of the world visited for the first time and yet there is a feeling so haunting in some instances as to be distressing—that it is all a repetition of something that has occurred in the indefinite past. This is a phenomenon so common that various theories have been offered in explanation. The most commonly accepted is that of the psychologist, who tells us that at the instant of the first glance the mind is pre-occupied and that a space of time, which may be infinitely minute and imperceptible, elapses before the intelligence can grasp the meaning of the sensual impression and interpret it into a cognizable fact. In the realm of the subconscious there is no measure of
Regulation of MicroRNA Expression and Abundance during Lymphopoiesis
Authors: Stefan Kuchen, Wolfgang Resch, Arito Yamane, Nan Kuo, Zhiyu Li, Tirtha Chakraborty, Lai Wei, Arian Laurence, Tomoharu Yasuda, Siying Peng, Jane Hu-Li, Kristina Lu, Wendy Dubois, Yoshiaki Kitamura, Nicolas Charles, Hong-wei Sun, Stefan Muljo, Pamela L. Schwartzberg, William E. Paul, John O'Shea, Klaus Rajewsky, Rafael Casellas
Journal: Immunity (2010)
Proposed Insurance Scheme
Authors: C. H. C. Thomas
Journal: BMJ (1965)

SIR,-The Times of 6 September had an interesting article concerning medical matters under the title " If Single-Handed Doctors Go."It was regretted that much of the personal touch will be lost.The grouping would, however, diminish the strain of unlimited liability which presses heavily on the single doctor.What other individuals or organization in the country would accept unlimited liability for service, particularly when the liability carries heavy penalties for the doctor and none for the individuals who abuse the service ?Surely this matter deserves more attention ?Could even a full-time salaried service carry the burden without restrictions on the user's side ?At present the sky is the limit.Some need aid, but that is no reason for giving it to all without restraint.There is no need, in effect, to burn the house down to get roast pig.-I am, etc.,
Police in Israel launch investigation into deaths of babies given formula milk
Authors: J. Siegel-Itzkovich
Journal: BMJ (2003)

The Israel police have launched a criminal investigation into the deaths from beriberi of two infants and the hospitalisation of 13 more who since August were fed a German made, non-dairy, baby formula made for sale only in Israel.

The special line of soya based formula—found by Israel's health ministry to “totally lack” the vital vitamin B-1 (thiamine)—was produced by the Humana company in Herford, Germany, one of the largest baby food manufacturers in Europe with an annual turnover of €;3bn (£2.1bn;$1.2bn).

After two days of insistent denials of any error or wrongdoing, Humana finally took “technical and scientific responsibility” for the failure.

The company's chairman, Albert Grossa Fray, said at a press conference …
Book Review The Practice of Neurosurgery Edited by George T. Tindall, Paul R. Cooper, and Daniel L. Barrow. 3496 pp. in three volumes, illustrated. Baltimore, Williams &amp; Wilkins, 1996. $595. 0-683-08266-3 Neurosurgery Second edition. Edited by Robert H. Wilkins and Setti S. Rengachary. 4271 pp. in three volumes, illustrated. New York, McGraw-Hill, 1996. $550. 0-07-079991-1
Authors: Robert R. Goodman
Journal: New England Journal of Medicine (1997)
The Many Faces of Bromocriptine
Authors: Samuel Vaisrub
Journal: JAMA (1976)

In 1676, Dodart observed that ergot inhibited lactation (<i>Journal des Savants</i>, 1676, p 76). Thus, we need not be astonished that 300 years later, bromocriptine (2-bromergokriptine, CB154), a semisynthetic ergot alkaloid free of the cardiovascular and oxytocic actions of its progenitor, has proved successful in suppressing puerperal lactation without producing undesirable side effects.<sup>1</sup> What comes as a surprise is the potential usefulness of bromocriptine in a variety of clinical conditions. Originally thought to be a stimulant to secretion of the hypothalamic prolactin-release inhibiting factor, the drug itself has since been shown to be such a factor. It acts directly on the pituitary cells by activating their dopamine receptors.<sup>2</sup>Because this dopaminergic action is not confined to prolactin-secreting cells, the drug (it has yet to be approved by the FDA) is being tried in the treatment of various disorders—galactorrhea, infertility, acromegaly, parkinsonism—that are susceptible to direct or indirect effects
Socioeconomic status and cutaneous malignant melanoma in Northern Europe
Authors: L.W. Idorn, H.C. Wulf
Journal: British Journal of Dermatology (2013)

Socioeconomic status (SES) is associated with cutaneous malignant melanoma (CMM) in Northern Europe, despite equal access to health care. SES per se is not responsible for this association, which must be ascribed to important risk factors for CMM such as intermittent ultraviolet radiation (UVR) exposure, and screening for CMM possibly owing to a greater knowledge and understanding of CMM. Our review of the literature showed that high SES is associated with increased risk of CMM, thinner tumours, increased survival and decreased mortality from CMM - the latter shown among women, and in recent studies also among men. There is evidence that high SES is associated with sun holidays, whereas low SES is associated with the use of sunbeds. Findings suggest that high SES is associated with the use of physicians and dermatologists for marks and moles, possibly owing to more knowledge and better understanding of CMM. We conclude that there has been a true increase in CMM incidence among high SES individuals in Northern Europe probably due to past intense intermittent UVR exposure, especially in connection with sun holidays. However, the increased risk of CMM and a better outcome of CMM in high SES individuals may also be conditioned by frequent recourse to physicians, which may be ascribed to more knowledge and better understanding of CMM, although more studies on this subject are warranted. Thicker CMM tumours and increased CMM mortality among low SES individuals in recent decades may reflect exposure to intermittent UVR, such as the use of sunbeds, as well as delayed diagnosis.
Bicarbonate and bicarbonate/lactate peritoneal dialysis solutions for the treatment of infusion pain
Authors: Robert A. Mactier, Timothy S. Sprosen, Ram Gokal, Paul F. Williams, Marianne Lindbergh, Ramesh B. Naik, Ulf Wrege, Knut-Christian Gröntoft, Rutger Larsson, Jonas Berglund, Anders P. Tranæus, Dirk Faict
Journal: Kidney International (1998)