tbuckley/cabot-search huggingface dataset:
Development of male contraceptive vaccine - a perspective
Authors: N. Moudgal
Journal: Human Reproduction Update (1997)

This paper reviews the recent advances that have occurred in the area of development of a male contraceptive vaccine. The vaccine candidates considered for review are hormone/hormone receptor-based proteins including luteinizing hormone-releasing hormone (LHRH)/LH, follicle stimulating hormone (FSH), as well as LH and FSH receptor proteins. The review also highlights the advances in our basic understanding of gonadotrophin action which have led to development of these vaccines. Focus is mainly on studies in the non-human primate which may be directly relevant to projected studies in the human. The data indicate that the vaccines are well tolerated by the primate (including the human based on limited data) and do not give rise to any known toxic symptoms or immediate health hazards. The response to the immunogen has been uniform and it may be possible to increase antibody titres as well as prolong the immune response by adding acceptable immune stimulators to the adjuvant cocktail and developing better immunization schedules or immunogen delivery systems. Contraceptive vaccines for the male are a feasible proposition and attention should now be focussed on evaluating carefully the bioefficacy of antibodies raised to recombinant ovine FSHbeta or FSH receptor protein fragments in both human and non-human primates. The advantage of the FSH/FSH receptor over the LHRH/LH-based vaccine lies in the fact that the former does not require an exogenous testosterone supplement to maintain accessory gland function, libido etc. The LHRH/LH-based vaccine results in azoospermia, while the FSH vaccine causes the production of low numbers of poor quality spermatozoa which are incapable of impregnating cycling females.
Species sensitivities and prediction of teratogenic potential.
Authors: J L Schardein, B A Schwetz, M F Kenel
Journal: Environmental Health Perspectives (1985)

Many chemicals shown to be teratogenic in laboratory animals are not known to be teratogenic in humans. However, it remains to be determined if the unresponsiveness of humans is due to lessened sensitivity, to generally subteratogenic exposure levels, or to the lack of an appropriate means of identifying human teratogens. On the other hand, with the exception of the coumarin anticoagulant drugs, those agents well accepted as human teratogens have been shown to be teratogenic in one or more laboratory species. Yet, no single species has clearly distinguished itself as being more advantageous in the detection of human teratogens over any other. Among the species used for testing, the rat and mouse most successfully model the human reaction, but the rabbit is less likely than other species to give a false positive finding. Among species less commonly used for testing, primates offered a higher level of predicability than others. Regarding concordance of target malformations, the mouse and rat produced the greatest number of concordant defects, but they also were responsible for the most noncorcordant responses as well. Since no other species is clearly more predictive of the human response, it is concluded that safety decisions should be based on all reproductive and developmental toxicity data in light of the agent's known pharmacokinetic, metabolic and toxicologic parameters.
Norepinephrine Turnover Is Increased in Suprabulbar Subcortical Brain Regions and Is Related to Whole-Body Sympathetic Activity in Human Heart Failure
Authors: Anuradha Aggarwal, Murray D. Esler, Gavin W. Lambert, Jacqueline Hastings, Leonie Johnston, David M. Kaye
Journal: Circulation (2002)

Background — Although it is established that heightened sympathetic drive exists in congestive heart failure (CHF), the reflex processes by which this may occur and the sites in the central nervous system that may be responsible for mediating this process are not yet fully elucidated. Methods and Results — Eight patients with moderate to severe CHF and 8 healthy control subjects underwent simultaneous arterial and bilateral internal jugular venous blood sampling and cerebral venous blood pool scanning for anatomical determination of the origin of internal jugular venous blood flow. We estimated sympathetic nervous activity by measuring total body norepinephrine (NE) spillover using radiotracer methodology and determined brain NE turnover by measuring the internal jugular overflow of NE and its lipophilic metabolites, 3-methoxy-4-hydroxyphenylglycol and 3,4-dihydroxyphenylglycol. Suprabulbar subcortical turnover of NE was significantly greater in CHF patients than in the healthy group (2.77±0.75 versus 0.66±0.40 nmol/min, P &lt;0.05). There was a significant positive correlation between suprabulbar subcortical turnover of NE and total body NE spillover ( r =0.62, P =0.01). Conclusions — This study, for the first time, demonstrates elevated suprabulbar subcortical noradrenergic activity in human CHF and identifies a positive correlation between this and the level of whole-body NE spillover. The findings suggest that the activation of noradrenergic neurons projecting rostrally from the brain stem mediates sympathetic nervous stimulation in CHF.
A study of the efficacy of carbon dioxide and pigment-specific lasers in the treatment of medium-sized congenital melanocytic naevi
Authors: P.J. August, J.E. Ferguson, V. Madan
Journal: British Journal of Dermatology (2011)

Treatment of medium-sized congenital melanocytic naevi (CMN) can be challenging.To present the results of treatment of 55 CMN with the carbon dioxide (CO(2) ) and pigment-specific lasers.CO(2) and Q-switched lasers (frequency-doubled Nd:YAG, Nd:YAG and alexandrite) were used to treat 55 CMN. Patients were treated at 3-month intervals until maximum clearance. Clinical response at 3-6 months after final treatment was graded as poor (< 50%), good (50-75%) or excellent (> 75%). Outcomes were evaluated on case note review and questionnaire.Thirty-six of the 55 CMN were macular and 19 were mammillated. Twenty-seven CMN were present on the head and neck. For macular CMN, outcomes were better for truncal CMN. Scarring and pallor were seen in three lower limb macular CMN treated with a CO(2) laser. Mammillated CMN on the head and neck showed most improvement. Pigment-specific lasers were of no additional benefit. Repigmentation occurred in 6% of macular and 21% of mammillated CMN. Partial or complete regimentation of CMN was reported by 46% of patients.Compared with macular CMN, mammillated CMN show a marginally better response to laser treatment. CMN on the limbs respond poorly. Pigment-specific lasers do not lighten mammillated CMN. Adverse effects can occur with CO(2) laser treatment of macular CMN on lower limbs.
Ecologic Studies in Epidemiology: Concepts, Principles, and Methods
Authors: Hal Morgenstern
Journal: Annual Review of Public Health (1995)

An ecologic study focuses on the comparison of groups, rather than individuals; thus, individual-level data are missing on the joint distribution, of variables within groups. Variables in an ecologic analysis may be aggregate measures, environmental measures, or global measures. The purpose of an ecologic analysis may be to make biologic inferences about effects on individual risks or to make ecologic inferences about effects on group rates. Ecologic study designs may be classified on two dimensions: (a) whether the primary group is measured (exploratory vs analytic study); and (b) whether subjects grouped by place (multiple-group study), by time (time-trend study), or place and time (mixed study). Despite several practical advantages of ecologic studies, there are many methodologic problems that severely limit causal inference, including ecologic and cross-level bias, problems of confounder control, within-group misclassification, lack of adequate data, temporal ambiguity, collinearity, and migration across groups.
Sunlamps and the risk of melanoma
Authors: S. P A Allwright
Journal: BMJ (1988)

and not be limited to conventions.Classical power determination does use a single alternative hypothesis, but power of the test is even greater if the true difference is larger than the posited clinically important difference.We think that Bayesian approaches offer great potential.As presently developed, however, the Bayesian method is difficult even for Bayesian statisticians and requires more research before it becomes practical.Development of Bayesian in- ference instruments that are easily employed by clinicians would greatly advance the usefulness of the Bayesian approach.
DISSEMINATED ELASTOSIS PERFORANS SERPIGINOSA IN FOUR MONGOLOIDS.
Authors: JAMES K. RASMUSSEN
Journal: British Journal of Dermatology (1972)

Journal Article DISSEMINATED ELASTOSIS PERFORANS SERPIGINOSA IN FOUR MONGOLOIDS: RECOGNITION OF RESIDUAL CHANGES Get access JAMES K. RASMUSSEN JAMES K. RASMUSSEN Department of Dermatolagy, University of Oregon Medical School, Portland, Oregen and Fairview Hospital and Training Center, Salem, Oregon, U.S.A Reprint requests should be addressed to Dr Rasmussen, Department of Dermatology, University of Oregon Medical School. 3181 S.W. Sam Jackson Park Rd., Portland, Oregon, 97201, U.S.A. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 86, Issue 1, 1 January 1972, Pages 9–13, https://doi.org/10.1111/j.1365-2133.1972.tb01885.x Published: 01 January 1972 Article history Accepted: 15 September 1971 Published: 01 January 1972
Community-Based Therapy for Multidrug-Resistant Tuberculosis in Lima, Peru
Authors: Carole Mitnick, Jaime Bayona, Eda Palacios, Sonya Shin, Jennifer Furin, Felix Alcántara, Epifanio Sánchez, Madeleny Sarria, Mercedes Becerra, Mary C. Smith Fawzi, Saidi Kapiga, Donna Neuberg, James H. Maguire, Jim Yong Kim, Paul Farmer
Journal: New England Journal of Medicine (2003)

Despite the prevalence of multidrug-resistant tuberculosis in nearly all low-income countries surveyed, effective therapy has been deemed too expensive and considered not to be feasible outside referral centers. We evaluated the results of community-based therapy for multidrug-resistant tuberculosis in a poor section of Lima, Peru.We describe the first 75 patients to receive ambulatory treatment with individualized regimens for chronic multidrug-resistant tuberculosis in northern Lima. We conducted a retrospective review of the charts of all patients enrolled in the program between August 1, 1996, and February 1, 1999, and identified predictors of poor outcomes.The infecting strains of Mycobacterium tuberculosis were resistant to a median of six drugs. Among the 66 patients who completed four or more months of therapy, 83 percent (55) were probably cured at the completion of treatment. Five of these 66 patients (8 percent) died while receiving therapy. Only one patient continued to have positive cultures after six months of treatment. All patients in whom treatment failed or who died had extensive bilateral pulmonary disease. In a multiple Cox proportional-hazards regression model, the predictors of the time to treatment failure or death were a low hematocrit (hazard ratio, 4.09; 95 percent confidence interval, 1.35 to 12.36) and a low body-mass index (hazard ratio, 3.23; 95 percent confidence interval, 0.90 to 11.53). Inclusion of pyrazinamide and ethambutol in the regimen (when susceptibility was confirmed) was associated with a favorable outcome (hazard ratio for treatment failure or death, 0.30; 95 percent confidence interval, 0.11 to 0.83).Community-based outpatient treatment of multidrug-resistant tuberculosis can yield high cure rates even in resource-poor settings. Early initiation of appropriate therapy can preserve susceptibility to first-line drugs and improve treatment outcomes.
Multiple Imputation
Authors: Peng Li, Elizabeth A. Stuart, David B. Allison
Journal: JAMA (2015)

In this issue of JAMA, Asch et al1 report results of a cluster-randomized clinical trial designed to evaluate the effects of physician financial incentives, patient incentives, or shared physician and patient incentives on low density lipoprotein cholesterol (LDL-C) levels among patients with high cardiovascular risk. Because 1 or more follow-up LDL-C measurements were missing for approximately 7% of participants, Asch et al used multiple imputation (MI) to analyze their data and concluded that shared financial incentives for physicians and patients, but not incentives to physicians or patients alone, resulted in the patients having lower LDL-C levels. Imputation is the process of replacing missing data with 1 or more specific values, to allow statistical analysis that includes all participants and not just those who do not have any missing data.

Missing data are common in research. In a previous JAMA Guide to Statistics and Methods, Newgard and Lewis2 reviewed the causes of missing data. These are divided into 3 classes: 1) missing completely at random, the most restrictive assumption, indicating that whether a data point is missing is completely unrelated to observed and unobserved data; 2) missing at random, a more realistic assumption than missing completely at random, indicating whether a data point is missing can be explained by the observed data; or 3) missing not at random, meaning that the missingness is dependent on the unobserved values. Common statistical methods used for handling missing values were reviewed.2 When missing data occur, it is important to not exclude cases with missing information (analyses after such exclusion are known as complete case analyses). Single-value imputation methods are those that estimate what each missing value might have been and replace it with a single value in the data set. Single-value imputation methods include mean imputation, last observation carried forward, and random imputation. These approaches can yield biased results and are suboptimal. Multiple imputation better handles missing data by estimating and replacing missing values many times.
Alternative and complementary medicine for asthma.
Authors: J B Morrison
Journal: Thorax (1992)

Alternative and complementary medicine for asthma Readers of the review by D J Lane and T V Lane (November 1991;46:787-97) might conclude that hypnosis has little to offer asthmatic patients.Although the report of Ewer and Stewart' is quoted as showing improvement in symptom scores and some peak expiratory flow rates and decreased use of bronchodilators, no mention is made of a 74-9% improvement (p < 0-01) in the degree of bronchial hyperresponsiveness to a stan- dardised methacholine challenge test.These authors state that "while our hypnotic tech- nique does not eliminate bronchial hyperresponsiveness it does provide a clinically useful and non-toxic adjuvant to drug treat- ment that might benefit about half of the asthmatic population."This approach could well reduce the use of the toxic drugs, such as troleandomycin, gold, azathioprine, and methotrexate, mentioned as steroid sparing agents by Shiner and Geddes.2The British Tuberculosis Association's study3 did not report negative results as stated in the review.On the contrary, "independent clinical assessors considered the asthma to be much better in 59% of the hypnosis groups and in 43% of the control group, the difference being significant."These results were obtained by using only direct suggestion under hypnosis plus autohypnosis daily; more advanced methods, such as reciprocal inhibition, were not used.In my own study4 it was possible to with- draw oral prednisolone or to reduce the dose in 14 of the 16 patients treated by hypnosis.The number of hospital admissions during the first year of hypnotherapy fell to 13, compared with 44 during the previous year.This represented a reduction of 249 hospital days, which, at 1988 costs (£170 per day), saved the NHS £42 330.As some 55 000 adults are admitted each year for asthma, savings to the NHS could be considerable if hypnotherapy were to be used more widely.
Mutations of the gene encoding the protein kinase A type I-α regulatory subunit in patients with the Carney complex
Authors: Lawrence S. Kirschner, J. Aidan Carney, Svetlana D. Pack, Susan E. Taymans, Christoforos Giatzakis, Yee Sook Cho, Yoon S. Cho-Chung, Constantine A. Stratakis
Journal: Nature Genetics (2000)
Epidermal Growth Factor Receptor(Egfr)Dephosphorylation and Growth Inhibition by Vinorelbine in Egfr-Mutated Cell Line
Authors: Hiroki Izumi, Tadashi Igishi, Shingo Matsumoto, Yasuto Ueda, Kenichi Takeda, Hirokazu Touge, Haruhiko Makino, Masahiro Kodani, S. Nirodi Chaitanya, Eiji Shimizu
Journal: Annals of Oncology (2014)
The therapeutic window of opportunity in rheumatoid arthritis: does it ever close?
Authors: Karim Raza, Andrew Filer
Journal: Annals of the Rheumatic Diseases (2015)

Studies of amnesic patients and animal models support a systems consolidation model, which posits that explicit memories formed in hippocampus are transferred to cortex over time<sup>1–6</sup>. Prelimbic cortex (PL), a subregion of the medial prefrontal cortex, is required for the expression of learned fear memories from hours after learning until weeks later<sup>7–12</sup>. While some studies suggested that prefrontal cortical neurons active during learning are required for memory retrieval<sup>13–15</sup>, others provided evidence for ongoing cortical circuit reorganization during memory consolidation<sup>10,16,17</sup>. It has been difficult to causally relate the activity of cortical neurons during learning or recent memory retrieval to their function in remote memory, in part due to a lack of tools<sup>18</sup>. Here we show that a new version of 'targeted recombination in active populations', TRAP2, has enhanced efficiency over the past version, providing brain-wide access to neurons activated by a particular experience. Using TRAP2, we accessed PL neurons activated during fear conditioning or 1-, 7-, or 14-day memory retrieval, and assessed their contributions to 28-day remote memory. We found that PL neurons TRAPed at later retrieval times were more likely to be reactivated during remote memory retrieval, and more effectively promoted remote memory retrieval. Furthermore, reducing PL activity during learning blunted the ability of TRAPed PL neurons to promote remote memory retrieval. Finally, a series of whole-brain analyses identified a set of cortical regions that were densely innervated by memory-TRAPed PL neurons and preferentially activated by PL neurons TRAPed during 14-day retrieval, and whose activity co-varied with PL and correlated with memory specificity. These findings support a model in which PL ensembles underlying remote memory undergo dynamic changes during the first two weeks after learning, which manifest as increased functional recruitment of cortical targets.
SIMULTANEOUS OCCURRENCE OF SCHIZOPHRENIA IN IDENTICAL TWINS
Authors: REBECCA SOLOMON, EUGENE L. BLISS
Journal: American Journal of Psychiatry (1956)

A study of identical twins who developed schizophrenic reactions simultaneously is presented. The vulnerability of the twins to schizophrenia is not explained by the data, but it is suggested that the symbiotic relationship existing between the two, was responsible for the coincidence of the two psychotic processes.
Promoting the Healthy Development of Adolescents
Authors: S G Millstein, E O Nightingale, A C Petersen, A M Mortimer, D A Hamburg
Journal: JAMA (1993)

ADOLESCENCE is a period of great risks and opportunities. The dramatic biological changes that accompany this transition are essentially the same as they have been for millennia, but the social context in which they occur is very different from earlier times and continues to change rapidly. Changes in the American family, the economic structure, the media, and the community have all affected the way adolescents live and interact with peers and with the rest of society. Within this social context, adolescents need to find ways to develop a vision of the future, to formulate an image of what adulthood offers and demands, and to work out a perception of opportunity and paths toward practical implementation of such opportunity.<sup>1</sup> The profoundly transformed conditions of contemporary society present remarkable opportunities to shape behavior in ways that establish healthy life-styles that are likely to endure through the adult years, yet they also
Hepatocellular Carcinoma from an Immunologic Perspective
Authors: Tim F. Greten, Austin G. Duffy, Firouzeh Korangy
Journal: Clinical Cancer Research (2013)

Abstract Hepatocellular carcinoma is the third most common cancer worldwide. It is an inflammation-associated cancer. Multiple investigators have demonstrated that analysis of the tumor microenvironment may be used to predict patient outcome, indicating the importance of local immune responses in this disease. In contrast with other types of cancer, in which surgery, radiation, and systemic cytotoxic chemotherapies dominate the treatment options, in hepatocellular carcinoma locoregional treatments are widely applied. Such treatments induce rapid tumor cell death and antitumor immune responses, which may favor or impair the patients' outcome. Recent immunotherapeutic studies demonstrating promising results include trials evaluating intratumoral injection of an oncolytic virus expressing granulocyte macrophage colony-stimulating factor, glypican-3 targeting treatments, and anti-CTLA4 treatment. Although some of these novel approaches may provide benefit as single agents, there is a clear opportunity in hepatocellular carcinoma to evaluate these in combination with the standard modalities to more effectively harness the immune response. Clin Cancer Res; 19(24); 6678–85. ©2013 AACR.
Eccentric treatment for patellar tendinopathy: a prospective randomised short-term pilot study of two rehabilitation protocols
Authors: Anna Frohm, Tönu Saartok, Kjartan Halvorsen, Per Renström
Journal: British Journal of Sports Medicine (2007)

To compare the efficacy and safety of two eccentric rehabilitation protocols for patients with symptomatic patellar tendinopathy. A new eccentric overload training device was compared with the present standard eccentric rehabilitation programme on a decline board.Prospective, randomised clinical trial.Sports rehabilitation clinic, university sports laboratory, supplemented with home exercises.20 competitive and recreational athletes, all with clinical diagnosis of patellar tendinopathy, verified by MRI or ultrasound imaging.A 12-week rehabilitation period, either with bilateral eccentric overload strength training using the Bromsman device twice a week or with unilateral eccentric body load training using a decline board twice a week, supplemented with daily home exercises.The primary outcome was pain and function, assessed by the Swedish Victorian Institute of Sport Assessment for Patella (VISA-P) score. Secondary outcome measures were isokinetic muscle torque, dynamic function and muscle flexibility, as well as pain level estimations using visual analogue scale (VAS). Side effects were registered.Both treatment groups improved in the short term according to the VISA-P scores during the 12-week rehabilitation period. However, there were no significant differences between the groups in terms of pain and function. After a 3-month rehabilitation period, most patients could be regarded as improved enough to be able to return to training and sports. No serious side effects were detected in either group.In patients with patellar tendinopathy pain, two-legged eccentric overload training twice per week, using the new device (Bromsman), was as efficient and safe as the present standard daily eccentric one-legged rehabilitation-training regimen using a decline board.
Effects of chitosan-nanoparticle-mediated tight junction opening on the oral absorption of endotoxins
Authors: Kiran Sonaje, Kun-Ju Lin, Michael T. Tseng, Shiaw-Pyng Wey, Fang-Yi Su, Er-Yuan Chuang, Chia-Wei Hsu, Chiung-Tong Chen, Hsing-Wen Sung
Journal: Biomaterials (2011)