tbuckley/cabot-search huggingface dataset:
Long-term Effects of an Early Childhood Intervention on Educational Achievement and Juvenile Arrest
Authors: Arthur J. Reynolds, Judy A. Temple, Dylan L. Robertson, Emily A. Mann
Journal: JAMA (2001)

ContextMost studies of the long-term effects of early childhood educational interventions are of demonstration programs rather than large-scale public programs. Previous studies of one of the oldest federally funded preschool programs have reported positive effects on school performance, but effects on educational attainment and crime are unknown.ObjectiveTo determine the long-term effectiveness of a federal center-based preschool and school–based intervention program for urban low-income children.Design, Setting, and ParticipantsFifteen-year follow-up of a nonrandomized, matched-group cohort of 1539 low-income, mostly black children born in 1980 and enrolled in alternative early childhood programs in 25 sites in Chicago, Ill.InterventionsThe Chicago Child-Parent Center (CPC) Program (n = 989 children) provides comprehensive education, family, and health services and includes half-day preschool at ages 3 to 4 years, half- or full-day kindergarten, and school-age services in linked elementary schools at ages 6 to 9 years. The comparison group (n = 550) consisted of children who participated in alternative early childhood programs (full-day kindergarten): 374 in the preschool comparison group from 5 randomly selected schools plus 2 others that provided full-day kindergarten and additional instructional resources and 176 who attended full-day kindergartens in 6 CPCs without preschool participation.Main Outcome MeasuresRates of high school completion and school dropout by age 20 years, juvenile arrests for violent and nonviolent offenses, and grade retention and special education placement by age 18 years.ResultsRelative to the preschool comparison group and adjusted for several covariates, children who participated in the preschool intervention for 1 or 2 years had a higher rate of high school completion (49.7 % vs 38.5%; P = .01); more years of completed education (10.6 vs 10.2; P = .03); and lower rates of juvenile arrest (16.9% vs 25.1%; P = .003), violent arrests (9.0% vs 15.3%; P = .002), and school dropout (46.7% vs 55.0%; P = .047). Both preschool and school-age participation were significantly associated with lower rates of grade retention and special education services. The effects of preschool participation on educational attainment were greater for boys than girls, especially in reducing school dropout rates (P = .03). Relative to less extensive participation, children with extended program participation from preschool through second or third grade also experienced lower rates of grade retention (21.9% vs 32.3%; P = .001) and special education (13.5% vs 20.7%; P = .004).ConclusionsParticipation in an established early childhood intervention for low-income children was associated with better educational and social outcomes up to age 20 years. These findings are among the strongest evidence that established programs administered through public schools can promote children's long-term success.
Programmes and principles in treatment of multidrug-resistant tuberculosis
Authors: Joia S Mukherjee, Michael L Rich, Adrienne R Socci, J Keith Joseph, Felix Alcántara Virú, Sonya S Shin, Jennifer J Furin, Mercedes C Becerra, Donna J Barry, Jim Yong Kim, Jaime Bayona, Paul Farmer, Mary C Smith Fawzi, Kwonjune J Seung
Journal: The Lancet (2004)
Many a slip?
Authors: A. Bush, C. Hogg
Journal: European Respiratory Journal (2009)

Cystic fibrosis (CF) is a common disease (up to 1 in 2,000 in some populations), and there is a simple, cheap and reliable diagnostic test which is within the compass of a hospital of any size. Yet even so, wrong diagnoses are not uncommon, because there is a long list of causes of a false-positive elevation in sweat electrolytes 1. The most important problem is lack of experience and attention to detail by the operator. Furthermore, borderline cases may need sophisticated testing to establish the diagnosis, such as nasal potential differences or complete sequencing of the CF gene. The consequences of a wrong diagnosis of CF are potentially serious, including the prescription of inappropriate medications, and the generation of a great deal of anxiety.

The situation with primary ciliary dyskinesia (PCD) is even more complex. The prevalence is debated, and although probably less than CF, PCD is still an important diagnosis to make. Diagnosis is delayed to a greater extent than CF 2, in part because many of the symptoms (cough and a runny nose) are common in normal children 3. The diagnosis is important; treatment leads to stabilisation of lung function, and those diagnosed late have worse spirometry 4, 5. Furthermore, PCD upper airway disease, specifically chronic secretory otitis media, has different implications than the same problem in otherwise normal children 6, 7. However, the diagnostic difficulties, particularly in terms of false positives, are much greater in …
Donor selection limits use of living-related liver transplantation
Authors: J RENZ
Journal: Hepatology (1995)

The purpose of this investigation was to assess the applicability of living-related liver transplantation in an established regional transplant program by determining the frequency of acceptable living donors from an unselected population of pediatric transplant candidates and identify specific factors limiting application of this technique. During the period May 1992 to May 1994, all children accepted as transplant candidates at the University of California-San Francisco were evaluated for potential living-related liver transplantation. Indications for transplantation and patient demographics represented the spectrum anticipated at a regional center. Donor evaluation was performed using a three-phase evaluation process we have previously reported. Retrospective analysis identified 75 potential donors for 38 pediatric candidates (age range, 17 days to 14.5 years; mean, 5.1 years). Twenty-three percent of potential donors declined evaluation. Of the 75 potential donors, only 10 (13%) were found to be acceptable for donation. The leading causes for donor declination were significant medical history (23%), ABO blood group incompatibility (23%), and psychosocial history (20%). Of the 38 recipient candidates, 9 (23%) were offered living-donor transplantation. Five patients have received living-donor transplantation, and 4 patients await the procedure when medical indications exist. Seventy-seven percent of recipient candidates received or are awaiting cadaveric transplantation. These results suggest that current donor criteria markedly limit the application of living-related liver transplantation.
Neoadjuvant Phase II Studies of Modified Methotrexate, Vinblastine, Doxorubicin, and Cisplatin in Muscle-Invasive Bladder Cancer
Authors: Bamidele A. Adesunloye
Journal: Journal of Clinical Oncology (2014)

TO THEEDITOR: TheclinicalefficacyofstandardMVAC(methotrexate30mg/m 2 ondays1,15,and22;vinblastine3mg/m 2 ondays 2,15,and22;doxorubicin30mg/m 2 onday2;andcisplatin70mg/m 2 on day 2 every 28 days) given preoperatively compared with surgery alone in bladder cancer was first demonstrated in a phase III clinical trial published in 2003. 1 Although there is no head-to-head comparison of neoadjuvant gemcitabine plus cisplatin (GC) to standard MVAC in phase III clinical trials, GC has been favored in the preoperative setting because of its milder toxicity profile. 2 The rationale is furtherbuttressedbythefactthatGCcomparedfavorablytostandard MVAC in the metastatic setting. 3 However, the data reported by Choueiri et al 4 and Plimack et al 5 in their respective phase II clinical trials are intriguing. Both studies showed that modified MVAC given every 2 weeks with growth factor support shortened the time to cystectomy and is both safe and effective. Although these two studies
Mental Health and Social Change: An Ecological Perspective
Authors: HARRY R. BRICKMAN
Journal: American Journal of Psychiatry (1970)

Through the community mental health movement, psychiatry has a chance to make an impact on the phenomenon of mental illness. But there is need to balance psychiatry's social control function with its function as an agent of social change. The author suggests that this can be done by means of a "rehumanizing" orientation; he cites the experience of the Los Angeles community mental health program to illustrate some of his concepts.
Characterisation and utility of thiopurine methyltransferase and thiopurine metabolite measurements in autoimmune hepatitis
Authors: Ulf Hindorf, Khatoon Jahed, Annika Bergquist, Hans Verbaan, Hanne Prytz, Sven Wallerstedt, Mårten Werner, Rolf Olsson, Einar Björnsson, Curt Peterson, Sven H.C. Almer
Journal: Journal of Hepatology (2009)
Randomised controlled trial of intravenous antibiotic treatment for cellulitis at home compared with hospital
Authors: Paul Corwin, Les Toop, Graham McGeoch, Martin Than, Simon Wynn-Thomas, J Elisabeth Wells, Robin Dawson, Paul Abernethy, Alan Pithie, Stephen Chambers, Lynn Fletcher, Dee Richards
Journal: BMJ (2004)

<h3>Abstract</h3> <b>Objectives</b> To compare the efficacy, safety, and acceptability of treatment with intravenous antibiotics for cellulitis at home and in hospital. <b>Design</b> Prospective randomised controlled trial. <b>Setting</b> Christchurch, New Zealand. <b>Participants</b> 200 patients presenting or referred to the only emergency department in Christchurch who were thought to require intravenous antibiotic treatment for cellulitis and who did not have any contraindications to home care were randomly assigned to receive treatment either at home or in hospital. <b>Main outcome measures</b> Days to no advancement of cellulitis was the primary outcome measure. Days on intravenous and oral antibiotics, days in hospital or in the home care programme, complications, degree of functioning and pain, and satisfaction with site of care were also recorded. <b>Results</b> The two treatment groups did not differ significantly for the primary outcome of days to no advancement of cellulitis, with a mean of 1.50 days (SD 0.11) for the group receiving treatment at home and 1.49 days (SD 0.10) for the group receiving treatment in hospital (mean difference 0.01 days, 95% confidence interval -0.3 to 0.28). None of the other outcome measures differed significantly except for patients9 satisfaction, which was greater in patients treated at home. <b>Conclusions</b> Treatment of cellulitis requiring intravenous antibiotics can be safely delivered at home. Patients prefer home treatment, but in this study only about one third of patients presenting at hospital for intravenous treatment of cellulitis were considered suitable for home treatment.
De novo nonsense mutations in ASXL1 cause Bohring-Opitz syndrome
Authors: Alexander Hoischen, Bregje W M van Bon, Benjamín Rodríguez-Santiago, Christian Gilissen, Lisenka E L M Vissers, Petra de Vries, Irene Janssen, Bart van Lier, Rob Hastings, Sarah F Smithson, Ruth Newbury-Ecob, Susanne Kjaergaard, Judith Goodship, Ruth McGowan, Deborah Bartholdi, Anita Rauch, Maarit Peippo, Jan M Cobben, Dagmar Wieczorek, Gabriele Gillessen-Kaesbach, Joris A Veltman, Han G Brunner, Bert B B A de Vries
Journal: Nature Genetics (2011)
Palifermin Reduces Severe Mucositis in Definitive Chemoradiotherapy of Locally Advanced Head and Neck Cancer: A Randomized, Placebo-Controlled Study
Authors: Quynh-Thu Le, Harold E. Kim, Charles J. Schneider, Györgyi Muraközy, Krzysztof Skladowski, Sabine Reinisch, Yuhchyau Chen, Michael Hickey, May Mo, Mon-Gy Chen, Dietmar Berger, Richard Lizambri, Michael Henke
Journal: Journal of Clinical Oncology (2011)

Purpose Oral mucositis (OM) is a debilitating toxicity of chemoradiotherapy for head and neck cancer (HNC). This randomized, placebo-controlled, double-blind study evaluated the efficacy and safety of palifermin to reduce OM associated with definitive chemoradiotherapy for locally advanced HNC. Patients and Methods Patients receiving conventionally fractionated radiotherapy (2.0 Gy/d, 5 days/wk to 70 Gy) with cisplatin (100 mg/m 2 on days 1, 22, and 43) received palifermin (180 μg/kg) or placebo before starting chemoradiotherapy and then once weekly for 7 weeks. The primary end point was the incidence of severe, observable, and functional OM (WHO grade 3 to 4). Results The palifermin (n = 94) and placebo (n = 94) arms were well balanced. The incidence of severe OM was significantly lower for palifermin than for placebo (54% v 69%; P = .041). In the palifermin arm, median time to severe OM was delayed (47 v 35 days), median duration of severe OM was shortened (5 v 26 days), and the incidence of xerostomia grade ≥ 2 was lower (67% v 80%), favoring palifermin; however, the differences were not significant after multiplicity adjustment. Opioid analgesic use, average mouth and throat soreness scores, and chemoradiotherapy compliance were not significantly different between treatment arms. Adverse events were similar between arms (98%, palifermin; 93%, placebo). The most common study drug–related adverse events were rash, flushing, and dysgeusia. After median follow-up of 25.8 months, overall survival and progression-free survival were similar between treatment arms. Conclusion Although palifermin reduced severe functional OM, its role in the management of locally advanced HNC during chemoradiotherapy remains to be elucidated.
<sup>90</sup>Yttrium-Ibritumomab-Tiuxetan as First-Line Treatment for Follicular Lymphoma: 30 Months of Follow-Up Data From an International Multicenter Phase II Clinical Trial
Authors: Christian W. Scholz, Antonello Pinto, Werner Linkesch, Ola Lindén, Andreas Viardot, Ulrich Keller, Georg Hess, Secondo Lastoria, Kristina Lerch, Ferdinando Frigeri, Manuela Arcamone, Andrea Stroux, Bernd Frericks, Christiane Pott, Antonio Pezzutto
Journal: Journal of Clinical Oncology (2012)

We report on a multicenter phase II trial of (90)yttrium-ibritumomab-tiuxetan ((90)YIT) as first-line stand-alone therapy for patients with follicular lymphoma (FL).Fifty-nine patients with CD20(+) FL grade 1 to 3a in stages II, III, or IV, age 50 years old or older requiring therapy were enrolled. They received (90)YIT according to standard procedure. If complete response (CR) or unconfirmed complete response (CRu) without evidence for minimal residual disease (MRD) 6 months after application of (90)YIT was achieved, patients were observed without further intervention. The same applied to patients with partial response (PR) or with stable disease (SD). Patients with CR but with persisting MRD were to receive a consolidation treatment with rituximab. Primary end point was the clinical and molecular response rate. Secondary end points were time to progression, safety, and tolerability.Six months after treatment with (90)YIT, 56% of the patients showed a CR or CRu and 31% achieved a PR. After a median follow-up of 30.6 months, the progression-free survival (PFS) was 26 months. There was a trend for shorter PFS in patients with increased lactate dehydrogenase (LDH). Of the 26 patients who had CR 12 months after (90)YIT, only three had relapsed. Median time to next treatment has not been reached. The most common toxicities were transient thrombocytopenia and leukocytopenia. Nonhematologic toxicities never exceeded grade 2 according to Common Terminology Criteria for Adverse Events (CTCAE v2.0).(90)YIT is well tolerated and achieves high response rates. Patients with increased LDH tend to relapse earlier, and individuals in remission 1 year after (90)YIT appear to have long- lasting responses.
Relation between respiratory symptoms, type of farming, and lung function disorders in farmers.
Authors: M Iversen, B Pedersen
Journal: Thorax (1990)

Respiratory symptoms and function were examined in a random sample of 181 farmers (124 pig farmers and 57 dairy farmers) with a mean age of 43 years. Wheezing and shortness of breath during work in the animal house were significantly associated with pig farming (odds ratio 11.4), current smoking (odds ratio 2.2), bronchial hyperreactivity (odds ratio 3.8), and low FEV1 (odds ratio 3.4). Pig farmers had a slightly lower FEV1 than dairy farmers (101% versus 104% predicted, NS). Symptomatic farmers had significantly lower FEV1 than symptomless farmers (93% versus 106% predicted). A multiple linear regression analysis of the cross sectional values of FEV1 showed that there was a decline in FEV1 associated with pig farming (-12 ml/year of pig farming) and smoking (-23 ml/pack year) in addition to the age related decline of 32 ml/year. A multiple linear regression analysis of PC20 histamine showed that bronchial reactivity increased with age, number of pack years, and number of years in pig farming. Work in closed pig rearing units is a pulmonary health hazard and causes decline in lung function.
Statistical methods for detecting molecular adaptation
Authors: Ziheng Yang, Joseph P. Bielawski
Journal: Trends in Ecology & Evolution (2000)

The past few years have seen the development of powerful statistical methods for detecting adaptive molecular evolution. These methods compare synonymous and nonsynonymous substitution rates in protein-coding genes, and regard a nonsynonymous rate elevated above the synonymous rate as evidence for darwinian selection. Numerous cases of molecular adaptation are being identified in various systems from viruses to humans. Although previous analyses averaging rates over sites and time have little power, recent methods designed to detect positive selection at individual sites and lineages have been successful. Here, we summarize recent statistical methods for detecting molecular adaptation, and discuss their limitations and possible improvements.
GMC orders urologist to be retrained
Authors: Owen Dyer
Journal: BMJ (2006)

A consultant urology surgeon has been ordered by the General Medical Council to undergo retraining, after a fitness to practise panel heard that his surgical technique was “highly flawed and likely to produce serious haemorrhaging.”

Hurais Syed, 51, was working as a locum consultant at the Dewsbury District Hospital, West Yorkshire, when he came to the attention of the GMC in 2000, soon after two of his surgical patients died.

John Hetherington, a 67 year old patient with a kidney tumour, died in the hospital's intensive care unit in February 2000, 35 …
Pharmacogenetics of Cancer Drugs
Authors: Daniel L. Hertz, James Rae
Journal: Annual Review of Medicine (2014)

The variability in treatment outcomes among patients receiving the same therapy for seemingly similar tumors can be attributed in part to genetics. The tumor's (somatic) genome largely dictates the effectiveness of the therapy, and the patient's (germline) genome influences drug exposure and the patient's sensitivity to toxicity. Many potentially clinically useful associations have been discovered between common germline genetic polymorphisms and outcomes of cancer treatment. This review highlights the germline pharmacogenetic associations that are currently being used to guide cancer treatment decisions, those that are most likely to someday be clinically useful, and associations that are well known but their roles in clinical management are not yet certain. In the future, germline genetic information will likely be available from tumor genetic analyses, creating an efficient opportunity to integrate the two genomes to optimize treatment outcomes for each individual cancer patient.
INDUCTION OF IMMUNOLOGICAL TOLERANCE TO A THYMUS-DEPENDENT ANTIGEN IN THE ABSENCE OF THYMUS-DERIVED CELLS
Authors: John W. Schrader
Journal: The Journal of Experimental Medicine (1974)

Specific immunological unresponsiveness was induced using thymus-dependent antigens in congenitally athymic (nu/nu) mice, in which no T-cell function has been demonstrated. The tolerance was induced in vivo by the injection of 5-10 mg of either FGG or DNP-HGG. Spleen cells from treated mice were tested in vitro for the ability to mount thymus-independent immune responses against FGG in the presence of polymerized flagellin POL, and the DNP determinant conjugated to POL. A specific deficiency in either the in vitro anti-FGG or anti-DNP response was demonstrated, depending on the antigen used for treatment of the spleen cell donor. Athymic mice treated with FGG were also tested by in vivo challenge with FGG given with POL as an adjuvant and were found to be hyporesponsive. Unresponsiveness to in vitro challenge was established by 24 h after the in vivo injection of FGG. It was found that the injection of POL with the FGG prevented the development of unresponsiveness, but not if the POL was given 24 h or more after the FGG. The unresponsiveness could not be overcome by confrontation with allogeneic spleen cells from CBA mice, although the presence of allogeneic spleen cells had a large amplifying effect on the response of control spleen cells. These experiments demonstrate a mechanism for the tolerization of bone marrow-derived cells by thymus-dependent antigens in the absence of the thymus.
A randomized trial of the efficacy of multidisciplinary care in heart failure outpatients at high risk of hospital readmission
Authors: Edward K Kasper, Gary Gerstenblith, Gail Hefter, Elizabeth Van Anden, Jeffrey A Brinker, David R Thiemann, Michael Terrin, Sandra Forman, Sheldon H Gottlieb
Journal: Journal of the American College of Cardiology (2002)
TGF-β signalling and reactive oxygen species drive fibrosis and matrix remodelling in myxomatous mitral valves
Authors: Michael A. Hagler, Thomas M. Hadley, Heyu Zhang, Kashish Mehra, Carolyn M. Roos, Hartzell V. Schaff, Rakesh M. Suri, Jordan D. Miller
Journal: Cardiovascular Research (2013)

Myxomatous mitral valve disease (MMVD) is associated with leaflet thickening, fibrosis, matrix remodelling, and leaflet prolapse. Molecular mechanisms contributing to MMVD, however, remain poorly understood. We tested the hypothesis that increased transforming growth factor-β (TGF-β) signalling and reactive oxygen species (ROS) are major contributors to pro-fibrotic gene expression in human and mouse mitral valves. Using qRT–PCR, we found that increased expression of TGF-β1 in mitral valves from humans with MMVD (n = 24) was associated with increased expression of connective tissue growth factor (CTGF) and matrix metalloproteinase 2 (MMP2). Increased levels of phospho-SMAD2/3 (western blotting) and expression of SMAD-specific E3 ubiquitin-protein ligases (SMURF) 1 and 2 (qRT–PCR) suggested that TGF-β1 signalling occurred through canonical signalling cascades. Oxidative stress (dihydroethidium staining) was increased in human MMVD tissue and associated with increases in NAD(P)H oxidase catalytic subunits (Nox) 2 and 4, occurring despite increases in superoxide dismutase 1 (SOD1). In mitral valves from SOD1-deficient mice, expression of CTGF, MMP2, Nox2, and Nox4 was significantly increased, suggesting that ROS can independently activate pro-fibrotic and matrix remodelling gene expression patterns. Furthermore, treatment of mouse mitral valve interstitial cells with cell permeable antioxidants attenuated TGF-β1-induced pro-fibrotic and matrix remodelling gene expression in vitro. Activation of canonical TGF-β signalling is a major contributor to fibrosis and matrix remodelling in MMVD, and is amplified by increases in oxidative stress. Treatments aimed at reducing TGF-β activation and oxidative stress in early MMVD may slow progression of MMVD.