tbuckley/cabot-search huggingface dataset:
Serotonergic function in aggressive and nonaggressive boys with attention deficit hyperactivity disorder
Authors: J M Halperin, V Sharma, L J Siever, S T Schwartz, K Matier, G Wornell, J H Newcorn
Journal: American Journal of Psychiatry (1994)

This study was designed to assess central serotonergic (5-HT) function in aggressive and nonaggressive boys with attention deficit hyperactivity disorder.Prolactin response to a challenge dose of the 5-HT agonist d,l-fenfluramine was assessed in 25 7-11-year-old boys with attention deficit hyperactivity disorder who were divided into aggressive and nonaggressive subgroups. In addition, the subgroups were compared on plasma catecholamine metabolites and platelet 5-HT.The aggressive group had a significantly greater prolactin response to the fenfluramine challenge than the nonaggressive subgroup. The groups did not differ on peripheral measures of neurotransmitter function.These data suggest that aggressive and nonaggressive children with attention deficit hyperactivity disorder differ in central 5-HT functioning.
Forensic psychiatry: profiles of two types of sex offenders
Authors: Fritz A. Henn, Marijan Herjanic, Robert H. Vanderpearl
Journal: American Journal of Psychiatry (1976)

The authors examined records of 239 individuals charged with sexual offenses and referred by the courts to a forensic service. Defendants charged with rape were typically under 30 with histories of antisocial behavior that included other types of violence. Major mental illness was rare in this group. Child molesters in the sample were of no particular age, usually had no history of violent behavior, and had a low incidence of psychosis. The most common secondary diagnosis in both groups was alcohol or drug abuse.
Early, Goal-Directed Resuscitation for Septic Shock.
Authors: Katja Auinger, Marco Maggiorini
Journal: New England Journal of Medicine (2015)

The Protocolised Management in Sepsis (ProMISe) trial (April 2 issue) completes a trio of studies that question the further application of early, goal-directed therapy (EGDT) as suggested by Rivers et al. In particular, these trials consistently show no survival benefit with regard to the mandated use of central venous oxygen saturation (ScvO$_2$) monitoring. However, it remains questionable whether the results of the three trials support this claim. According to the EGDT protocol, an ScvO$_2$ value of less than 70% is a trigger for hemodynamic intervention. Unlike in the study by Rivers et al., the reported mean values at baseline in all three trials do not require any intervention. Whether the reported survival benefit in the study by Rivers et al. is based on the treatment of patients with initially extremely low ScvO$_2$ values and determines the targeted patient population that benefits from EGDT remains, therefore, unanswered. Pope et al. reported increased mortality when ScvO$_2$ values were initially low ( 80%). Unless subgroup analyses and further studies that focus on these high-risk patients do not rule out a survival benefit, the final conclusion of the three trials cannot be supported.
Time trends in surgery for lung cancer in France from 2005 to 2012: a nationwide study
Authors: Marie-Catherine Morgant, Pierre-Benoit Pagès, Bastien Orsini, Pierre-Emmanuel Falcoz, Pascal-Alexandre Thomas, Françoise Le Pimpec Barthes, Marcel Dahan, Alain Bernard
Journal: European Respiratory Journal (2015)

The aim of this study was to assess the evolution of survival in patients treated surgically for non-small cell lung cancer (NSCLC) between 2005 and 2012.From January 2005 to December 2012, 34 006 patients underwent pulmonary resection for NSCLC and were included in the French national database Epithor. Patients' characteristics, procedures and survival were analysed. Survival according to the management was evaluated for each 2-year period separately: 2005-2006, 2007-2008, 2009-2010 and 2011-2012.The proportions of early-stage cancers and adenocarcinomas increased significantly over the periods. 3-year overall survival (OS) increased significantly from 80.5% for the first period to 81.4% for the last period. For the periods 2005-2006 and 2007-2008, 3-year OS was lower after segmentectomy than after lobectomy (77 and 73% versus 82 and 83%, respectively). For the periods 2009-2010 and 2011-2012, 3-year OS in the two sub-groups was similar. OS after bi-lobectomy or pneumonectomy was lower than after lobectomy for all periods analysed. Systematic nodal dissection increased OS for all periods. Chemotherapy but not radiotherapy improved OS in the first 12 postoperative months for all periods.Changes in histological type and stage linked to advances in surgical and medical practices since 2005 led to an increase in OS in patients with surgical-stage NSCLC.
Current and Projected Heat-Related Morbidity and Mortality in Rhode Island
Authors: Samantha L. Kingsley, Melissa N. Eliot, Julia Gold, Robert R. Vanderslice, Gregory A. Wellenius
Journal: Environmental Health Perspectives (2015)

Background:Climate change is expected to cause increases in heat-related mortality, especially among the elderly and very young. However, additional studies are needed to clarify the effects of heat on morbidity across all age groups and across a wider range of temperatures.Objectives:We aimed to estimate the impact of current and projected future temperatures on morbidity and mortality in Rhode Island.Methods:We used Poisson regression models to estimate the association between daily maximum temperature and rates of all-cause and heat-related emergency department (ED) admissions and all-cause mortality. We then used downscaled Coupled Model Intercomparison Project Phase 5 (CMIP5; a standardized set of climate change model simulations) projections to estimate the excess morbidity and mortality that would be observed if this population were exposed to the temperatures projected for 2046–2053 and 2092–2099 under two representative concentration pathways (RCP): RCP 8.5 and 4.5.Results:Between 2005 and 2012, an increase in maximum daily temperature from 75 to 85°F was associated with 1.3% and 23.9% higher rates of all-cause and heat-related ED visits, respectively. The corresponding effect estimate for all-cause mortality from 1999 through 2011 was 4.0%. The association with all-cause ED admissions was strongest for those < 18 or ≥ 65 years of age, whereas the association with heat-related ED admissions was most pronounced among 18- to 64-year-olds. If this Rhode Island population were exposed to temperatures projected under RCP 8.5 for 2092–2099, we estimate that there would be 1.2% (range, 0.6–1.6%) and 24.4% (range, 6.9–41.8%) more all-cause and heat-related ED admissions, respectively, and 1.6% (range, 0.8–2.1%) more deaths annually between April and October.Conclusions:With all other factors held constant, our findings suggest that the current population of Rhode Island would experience substantially higher morbidity and mortality if maximum daily temperatures increase further as projected.Citation:Kingsley SL, Eliot MN, Gold J, Vanderslice RR, Wellenius GA. 2016. Current and projected heat-related morbidity and mortality in Rhode Island. Environ Health Perspect 124:460–467; http://dx.doi.org/10.1289/ehp.1408826
Abstract 5608: Prognostic Impact of the Baseline White Blood Cell Count in Patients with Acute Myocardial Infarction Undergoing Primary PCI: Results from the HORIZONS-AMI trial
Authors: Roxana Mehran, George D Dangas, Helen Parise, Giulio Guagliumi, Bernard Witzenbichler, Liliana Grinfeld, Jan Z Peruga, Ran Kornowski, Darius Dudek, Rita Hoard, Adnan Kastrati, Deutsches Herzzentrum, Somjot Brar, Roland Wu, Damiana Fiscella, Bruce Brodie, Alexandra J Lansky, Gregg W Stone
Journal: Circulation (2008)

Background: Inflammation plays a crucial role in atherosclerosis. Previous studies have suggested an association between elevated white blood cell (WBC) and adverse outcomes in patients with ST-elevation acute myocardial infarction (STEMI). We sought to determine the relationship between admission WBC count and mortality in patients with STEMI in the HORIZONS-AMI trial. Methods: HORIZONS-AMI enrolled 3602 patients with STEMI undergoing primary PCI. We compared rates of 30-day major adverse cardiac events (MACE: death, reinfarction, target vessel revascularization for ischemia, or stroke), non-CABG major bleeding, and net adverse clinical events (NACE: MACE or major bleeding) in patients with baseline WBC count &gt;12,000 cells/mm 3 vs ≤12,000 cells/mm 3 . Results: Of the 3497 patients with baseline WBC data, 2206 (63.1%) had a WBC count of ≤12,000 and 1291 (38.9%) had a WBC of &gt;12,000 (median 10,800 mm 3 , mean 11,700 mm 3 ). Patients with WBC ≤12,000 were older, had more hypertension, hyperlipidemia, diabetes, prior MI, and prior CABG. Compared to patients with WBC ≤12,000, those with WBC &gt;12,000 had significantly higher rates of 30-day adverse outcomes (Table ). By multivariate analyses, WBC &gt;12,000 was an independent predictor of 30-day mortality (HR [95% CI] = 2.51 [1.61–3.91], p30.001), MACE (1.82 [1.36, 2.44], p&lt;0.0001), and major bleeding (1.52 [1.16 –1.99], p=0.003). Conclusions: In patients presenting with STEMI undergoing primary PCI, an elevated WBC count identifies a high risk cohort with significantly higher mortality, MACE and major bleeding at 30-days. These results further support the pivotal role of inflammation in ACS/AMI.
Development of Patient-specific AAV Vectors After Neutralizing Antibody Selection for Enhanced Muscle Gene Transfer
Authors: Chengwen Li, Shuqing Wu, Blake Albright, Matthew Hirsch, Wuping Li, Yu-Shan Tseng, Mavis Agbandje-McKenna, Scott McPhee, Aravind Asokan, R Jude Samulski
Journal: Molecular Therapy (2015)

A major hindrance in gene therapy trials with adeno-associated virus (AAV) vectors is the presence of neutralizing antibodies (NAbs) that inhibit AAV transduction. In this study, we used directed evolution techniques in vitro and in mouse muscle to select novel NAb escape AAV chimeric capsid mutants in the presence of individual patient serum. AAV mutants isolated in vitro escaped broad patient-specific NAb activity but had poor transduction ability in vivo. AAV mutants isolated in vivo had enhanced NAb evasion from cognate serum and had high muscle transduction ability. More importantly, structural modeling identified a 100 amino acid motif from AAV6 in variable region (VR) III that confers this enhanced muscle tropism. In addition, a predominantly AAV8 capsid beta barrel template with a specific preference for AAV1/AAV9 in VR VII located at threefold symmetry axis facilitates NAb escape. Our data strongly support that chimeric AAV capsids composed of modular and nonoverlapping domains from various serotypes are capable of evading patient-specific NAbs and have enhanced muscle transduction. A major hindrance in gene therapy trials with adeno-associated virus (AAV) vectors is the presence of neutralizing antibodies (NAbs) that inhibit AAV transduction. In this study, we used directed evolution techniques in vitro and in mouse muscle to select novel NAb escape AAV chimeric capsid mutants in the presence of individual patient serum. AAV mutants isolated in vitro escaped broad patient-specific NAb activity but had poor transduction ability in vivo. AAV mutants isolated in vivo had enhanced NAb evasion from cognate serum and had high muscle transduction ability. More importantly, structural modeling identified a 100 amino acid motif from AAV6 in variable region (VR) III that confers this enhanced muscle tropism. In addition, a predominantly AAV8 capsid beta barrel template with a specific preference for AAV1/AAV9 in VR VII located at threefold symmetry axis facilitates NAb escape. Our data strongly support that chimeric AAV capsids composed of modular and nonoverlapping domains from various serotypes are capable of evading patient-specific NAbs and have enhanced muscle transduction.
Abstract 16332: A Novel Mouse Model of Hemorrhagic Arteriovenous Malformation in the Brain and Spinal Cord
Authors: Caitlin Allen, Dan Ouyang, Nathan Yanasak, Tsugio Seki
Journal: Circulation (2011)

Hemorrhage from neurological arteriovenous malformation (AVM) may cause severe neurological deficit or death. A limit in studying neurological AVM and its rupture has been the lack of appropriate m...
Abstract 16285: Advanced Glycation End Products Disrupts Calcium Homeostasis Leading to ER Stress and Cardiac Contractile Dysfunction in Diabetes
Authors: Yingmei Zhang, Sara A Babcock, Shiyan Li, Jun Ren
Journal: Circulation (2011)

Diabetes mellitus leads to accumulation of reactive oxygen species, oxidative stress and cardiac contratile dysfunction in the heart. Although several rationales have been speculated, the precise m...
Phase I trial of oral topotecan with intravenous carboplatin in patients with advanced cancer
Authors: J. R. Ackler, A. Desai, J. C. Leighton, W. J. Tester
Journal: Journal of Clinical Oncology (2004)

3184 Background: Topotecan is an active agent, approved for second line treatment of ovarian and small cell lung cancer. Its use has been limited by leukopenia and its schedule of drug administration requiring 5 daily intravenous infusions. Synergy and schedule dependence has been reported with platinum compounds in some preclinical models. We sought to develop an oral five-day regimen that could be safely administered with carboplatin. Methods: Patients eligible for this trial included those with advanced solid tumors who had disease progression on standard chemotherapy, ECOG performance status < 2, calculated creatinine clearance > 60, prior radiotherapy to less than 20% bone marrow, WBC > 3.5, platelet count > 100, and signed informed consent. The population studied had received 1–3 (median 2) prior chemotherapy regimens. A total of 12 patients received 24 cycles of therapy. Six patients in the first cohort received oral topotecan 1.0 mg/m2 daily x 5. The second cohort of six patients received the same schedule of oral topotecan at 1.4 mg/m2 daily x5. The initial three patients of both cohorts received carboplatin AUC 5 on day 1 and the second three patients of both cohorts received carboplatin AUC 5 on day 5. Results: Dose-limiting toxicity was reached in the second cohort with 3/6 patients experiencing grade 4 dose-limiting thrombocytopenia. All grade 3–4 toxicity (per patient) observed in these 12 patients included anemia (3), granulocytopenia (6), thrombocytopenia (6), diarrhea (1) and febrile neutropenia (1). No patient developed thrombocytopenic bleeding. No responses were observed. The median time to progression was 8 weeks in this population of pre-treated patients. Conclusion: The maximally tolerated dose of oral topotecan given on this schedule is 1.4 mg/m2 daily x 5 plus carboplatin AUC 5. The day of administration of carboplatin (day 1 vs. day 5) made little impact on toxicity. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Aventis Aventis
Factors associated with local, distant, overall recurrence in surgically-resected non-small cell lung cancer and the role of diabetes in local recurrence
Authors: J. M. Varlotto, J. C. Flickinger, L. N. Medford-Davis, M. M. DeCamp, A. Recht
Journal: Journal of Clinical Oncology (2008)

7572 Background: To assess surgical, histopathologic and patient-related factors associated with local, distant and overall recurrence in patients with Stages I-IIIA Non-Small Cell Cancer (NSCLC) who underwent a definitive surgical resection ± adjuvant chemotherapy. Methods: 336 Consecutive Patients who underwent a definitive Surgical Resection ± adjuvant chemotherapy for NSCLC from 2000–2004 were qualified for analysis if they did not receive any adjuvant/neo-adjuvant Radiotherapy, had at least three months of follow-up, and did not have a history of other cancers within 5 years of the diagnosis of their NSCLC. Univariate and Multi-variate analyses were performed to assess risk factors for local and distal recurrence. Recurrence rates at 2,3, and 5 years were calculated by the methods of Kaplan-Meier. Results: Median follow-up of all patients was 36.95 months. Local Failure rates at 2,3 and 5 years was 16, 25, and 46%. The most common sites of local recurrence were the ipsilateral lung (28.8%), ipsilateral mediastinum (20.2%), and the stump/staple line (14.4%). Multi-variate analysis revealed that local recurrence was significantly associated with Lymphatic/Vascular Invasion (LVI), and the presence of diabetes at diagnosis (independent of BMI). Distal Recurrence Rates were 14, 19, and 32% at 2,3, and 5 years. The most common sites of distal recurrence were the contralateral lung (27%), bone (20%), and the brain (19%). Multi-variate Analysis revealed that distal recurrence was significantly higher with patients requiring a pneumonectomy, having symptoms of coughing, and increasing TNM stage. Overall recurrence was significantly associated with LVI and increasing tumor diameter. Conclusions: Because some patients with small local recurrences may benefit from aggressive therapy, patient with surgically-resected lung cancer who have diabetes at diagnosis and the presence of LVI in their tumor specimen may benefit from close surveillance. Multi-variate Analysis for Local, Distal and Overall Recurrence Multivariate Local Recurrence P-value HRR PNI or LNI 0.000107 2.718881 Diabetes 0.00688 1.936824 Multivariate Distal Recurrence Pneumonectomy 0.004608 3.043912 Stage 0.00427 1.550505 Cough 0.012976 2.050708 Multivariate Any Recurrence PNI or LNI 0.001615 2.391313 Tumor Diameter 0.015026 1.126996 No significant financial relationships to disclose.
Abstract 16004: Crystal Structure of TBX5 DNA Binding Domain and NKX2.5 Homeodomain in Complex With ANF-252 Motif
Authors: Lagnajeet Pradhan, Sunil K Gopal, Sandhya Ramesh, Hideko Kasahara, Hyun-Joo Nam
Journal: Circulation (2011)

Background Heart morphogenesis is controlled by combinatorial interactions of core cardiac transcription factors such as TBX5 and NKX2.5. Mutations in TBX5 and NKX2.5 result in congenital heart dis...
Active c-Met signaling contributes to enhanced metastatic potential of nasopharyngeal carcinoma (NPC)
Authors: Vivian Lui, Elaine Wong, Daisy Yau, Chin Chan, Anthony Chan
Journal: Cancer Research (2007)

2078   Nasopharyngeal cancer (NPC) is highly prevalent in Southeast Asia. Although NPC is highly curable at an early stage, the mortality rate of recurrent and metastatic NPC remains high even with the most aggressive radiochemotherapy. The mechanism governing the high metastatic potential of NPC is largely unexplored. Previous clinical studies implicated that c-Met may be crucial for the malignant progression of NPC. In this study, we investigate the contribution of c-Met signaling to NPC tumorigenesis. c-Met protein is overexpressed in all NPC cell lines examined (CNE-1, CNE-2, HK1, HONE-1 and C666-1) when compared to normal epithelial control cell line, Het-1A (immortalized by SV40 large T antigen, from ATCC, USA). HGF, the ligand of c-Met, is expressed at detectable levels in NPC cells (high levels in HONE-1 and low levels in CNE-1) by RT-PCR. In two representative NPC cell lines, HONE-1 and CNE-2, HGF (20ng/ml) induced a rapid phosphorylation of c-Met (as early as 2 mins; by immunoprecipitation), and subsequent activation of MAPK (p-p42/44 MAPK) and STAT3 (p-STAT3-Tyr705). Sustained HGF-induced MAPK activation was observed up to 48 hrs. In both NPC cell lines, HGF induced a dose-dependent increase in cell proliferation at 48 hrs. HGF seems to be a stronger mitogen than EGF at equal concentration of 50ng/ml (by cell counting experiment at 48 hrs) in both cell lines. HGF enhanced HONE-1 proliferation by 128.8 ± 7.17 % and EGF by 48.11 ± 7.37 %, while in CNE-2, HGF enhanced cell growth by 44.06 ± 7.93 % and EGF by 28.05 ± 7.12 %, respectively. The effects of c-Met activation by HGF on NPC invasiveness and metastatic potential were then examined. HGF treatment induced a dose-dependent increase cell-cell dissociation (by cell scattering assay at 24 hrs) and cellular motility (by wound healing assay at 24 hrs) in HONE-1 and CNE-2. Moreover, specific inhibition of c-Met expression by a c-Met shRNA expression vector abrogated HONE-1 cell growth by 70% at 3 days after transfection when compared to control vector. The invasiveness (assayed by Matrigel Invasion assay) of c-Met shRNA transfected HONE-1 cells was significantly reduced by 46 % and 92 % (p=0.0017) in the absence of HGF and presence of HGF (20 ng/ml) respectively when compared with the control shRNA transfectant. Significant abrogation of HGF-induced cell scattering and migration (by wound healing assay at 24 hrs) was observed with the c-Met shRNA, but not the control shRNA transfectants. In summary, our results suggest that c-Met signaling contributes to the malignant phenotype of NPC.  Financial Support: Endowment Fund Research Grant for 2006/2007, United College, CUHK (Grant awarded to VWYL).
Psychological benefits of Spiritual Baptist "mourning," II: An empirical assessment
Authors: E E Griffith, G E Mahy, J L Young
Journal: American Journal of Psychiatry (1986)

Members of a West Indian Christian sect called the Spiritual Baptists participate in a "mourning" ritual that is characterized by praying, fasting, and the experiencing of dreams and visions while in isolation. Sixteen individuals who underwent mourning were evaluated with the SCL-90-R before and after the ritual. In general, the mourners showed significant improvement on the self-report scales.
Military approach to medical planning in humanitarian operations
Authors: Martin C M Bricknell, Tracey MacCormack
Journal: BMJ (2005)

Military medical forces may be the only medical services available in the immediate aftermath of conflict and are often required to coordinate the re-establishment of civilian services. UK military medical services have a long history of providing assistance in humanitarian emergencies.

Military medical planners apply a structured approach to determine the requirements for medical support to military operations. This “medical estimate” has two outputs. The first develops health promotion and preventive medicine advice and actions to help maintain the physical, psychological, and social health of the military force. The second output develops missions and tasks for the medical elements of the force.

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British Army ambulance in a refugee camp in Kosovo, 1999. Military medical forces may be the only medical services available in the immediate aftermath of conflict

In military medical planning, a planner is given a mission by headquarters. The planner is required to assess this mission to establish missions for his or her subordinates. If the mission is unclear the planner may seek further information from intelligence reports or reconnaissance. Thus, the critical task is interpretation of the mission in order to give subordinates instructions to fulfil the planner's interpretation of the problem.

Background information —At the start of an estimate it is important to assemble background information. This might include maps, situation reports for the local area, news reports, and information about prevalent diseases. Internet sites hosted by international aid organisations such as the United Nations, World Health Organization, US Centers for Disease Control, and the UK Health Protection Agency may contain useful information. Less formal sites such as ReliefWeb and Well Diggers Workstation contain much practical information.

View this table:

The five steps of the military medical estimate



An estimate follows five steps: mission analysis, evaluation of factors, consideration of courses of action, commander's decision, and development of the …

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