tbuckley/cabot-search huggingface dataset:
Institutional Rearing and Psychiatric Disorders in Romanian Preschool Children
Authors: Charles H. Zeanah, Helen L. Egger, Anna T. Smyke, Charles A. Nelson, Nathan A. Fox, Peter J. Marshall, Donald Guthrie
Journal: American Journal of Psychiatry (2009)

There is increasing interest in the relations between adverse early experiences and subsequent psychiatric disorders. Institutional rearing is considered an adverse caregiving environment, but few studies have systematically examined its effects. This study aimed to determine whether removing young children from institutional care and placing them with foster families would reduce psychiatric morbidity at 54 months of age.Young children living in institutions in Bucharest were enrolled when they were between 6 and 30 months of age. Following baseline assessment, 136 children were randomly assigned to care as usual (continued institutional care) or to removal and placement in foster care that was created as part of the study. Psychiatric disorders, symptoms, and comorbidity were examined by structured psychiatric interviews of caregivers of 52 children receiving care as usual and 59 children in foster care when the children were 54 months of age. Both groups were compared to 59 typically developing, never-institutionalized Romanian children recruited from pediatric clinics in Bucharest. Foster care was created and supported by social workers in Bucharest who received regular consultation from U.S. clinicians.Children with any history of institutional rearing had more psychiatric disorders than children without such a history (53.2% versus 22.0%). Children removed from institutions and placed in foster families were less likely to have internalizing disorders than children who continued with care as usual (22.0% versus 44.2%). Boys were more symptomatic than girls regardless of their caregiving environment and, unlike girls, had no reduction in total psychiatric symptoms following foster placement.Institutional rearing was associated with substantial psychiatric morbidity. Removing young children from institutions and placing them in families significantly reduced internalizing disorders, although girls were significantly more responsive to this intervention than boys.
Determinants of oesophageal 'alkaline' pH environment in controls and patients with gastro-oesophageal reflux disease.
Authors: S Singh, L A Bradley, J E Richter
Journal: Gut (1993)

The determinants of the oesophageal alkaline pH environment are poorly understood. Saliva (pH 6.4-7.8) may be a major contributor, although some argue the importance of refluxed alkaline duodenal contents. Acid and alkaline reflux parameters were studied over 2 days in 30 subjects (control, oesophagitis and Barrett's patients; 10 each) using glass pH electrodes. In phase 1, one pH electrode was placed 1 cm below the upper oesophageal sphincter to assess the influence of saliva and the other 5 cm above the lower oesophageal sphincter. Phase 2 was identical except that one pH probe was 5 cm below the lower oesophageal sphincter to record duodenogastric reflux. Patient groups spent, on average, 50 fold more time during the upright and supine periods at acidic pH than controls. Saliva was responsible for the percentage of time the pH > 7 and contributed significantly to the percentage of time the pH > 6 in both the proximal and distal oesophagus of control subjects, as shown by an absence of pH > 7 and a significant (p < 0.001) fourfold decrease in pH > 6 during sleep. A similar pattern was seen in the proximal oesophagus of both reflux groups. The reflux and Barrett's patients, however did not show a significant decrease in the percentage of time the pH > 6 at night in the distal oesophagus suggesting a relative increase in 'alkaline' exposure from another source. This was not because of duodenogastric reflux as the corresponding pH rises in the fundus of the stomach were non-existent. Although this was not studied specifically, it is believed to be a protective meachanism, the result of alkaline secretion produced by submucosal oesophageal glands.
Touch and Go: Decision-Making Mechanisms in Somatosensation
Authors: Ranulfo Romo, Emilio Salinas
Journal: Annual Review of Neuroscience (2001)

▪ Abstract A complex sequence of neural events unfolds between sensory receptor activation and motor activity. To understand the underlying decision-making mechanisms linking somatic sensation and action, we ask what components of the neural activity evoked by a stimulus are directly related to psychophysical performance, and how are they related. We find that single-neuron responses in primary and secondary somatosensory cortices account for the observed performance of monkeys in vibrotactile discrimination tasks, and that neuronal and behavioral responses covary in single trials. This sensory activity, which provides input to memory and decision-making mechanisms, is modulated by attention and behavioral context, and microstimulation experiments indicate that it may trigger normal perceptual experiences. Responses recorded in motor areas seem to reflect the output of decision-making operations, which suggests that the ability to make decisions occurs at the sensory-motor interface.
Phase I Dose-Escalation Study of Recombinant Human Apo2L/TRAIL, a Dual Proapoptotic Receptor Agonist, in Patients With Advanced Cancer
Authors: Roy S. Herbst, S. Gail Eckhardt, Razelle Kurzrock, Scot Ebbinghaus, Peter J. O'Dwyer, Michael S. Gordon, William Novotny, Meredith A. Goldwasser, Tanyifor M. Tohnya, Bert L. Lum, Avi Ashkenazi, Adrian M. Jubb, David S. Mendelson
Journal: Journal of Clinical Oncology (2010)

Purpose Apoptosis ligand 2/tumor necrosis factor–related apoptosis-inducing ligand (Apo2L/TRAIL)—a member of the tumor necrosis factor cytokine family—induces apoptosis by activating the extrinsic pathway through the proapoptotic death receptors DR4 and DR5. Recombinant human Apo2L/TRAIL (rhApo2L/TRAIL) has broad potential as a cancer therapy. To the best of our knowledge, this is the first in-human clinical trial to assess the safety, tolerability, pharmacokinetics, and antitumor activity of multiple intravenous doses of rhApo2L/TRAIL in patients with advanced cancer. Patients and Methods This phase I, open-label, dose-escalation study treated patients with advanced cancer with rhApo2L/TRAIL doses ranging from 0.5 to 30 mg/kg/d, with parallel dose escalation for patients without liver metastases and with normal liver function (cohort 1) and for patients with liver metastases and normal or mildly abnormal liver function (cohort 2). Doses were given daily for 5 days, with cycles repeating every 3 weeks. Assessments included adverse events (AEs), laboratory tests, pharmacokinetics, and imaging to evaluate antitumor activity. Results Seventy-one patients received a mean of 18.3 doses; seven patients completed all eight treatment cycles. The AE profile of rhApo2L/TRAIL was similar in cohorts 1 and 2. The most common AEs were fatigue (38%), nausea (28%), vomiting (23%), fever (23%), anemia (18%), and constipation (18%). Liver enzyme elevations were concurrent with progressive metastatic liver disease. Two patients with sarcoma (synovial and undifferentiated) experienced serious AEs associated with rapid tumor necrosis. Two patients with chondrosarcoma experienced durable partial responses to rhApo2L/TRAIL. Conclusion At the tested schedule and dose range, rhApo2L/TRAIL was safe and well tolerated. Dose escalation achieved peak rhApo2L/TRAIL serum concentrations equivalent to those associated with preclinical antitumor efficacy.
On the Pathogenesis of the Uremic State
Authors: Neal S. Bricker
Journal: New England Journal of Medicine (1972)

MY comments represent an effort to summarize some of the very recent observations that my colleagues and I have made regarding the impact of chronic progressive renal disease on the functional characteristics of the afflicted kidney and, in a broader sense, on the functional characteristics of the whole organism. The investigations that formed the background for the most recent chapter in a continuing search for information about renal disease arose entirely out of a clinical arena.The initial questions that we asked some years ago reflected uncertainty about many fundamental aspects of renal function in patients with renal disease. The . . .
Non-participation in sports injury research: why football players choose not to be involved: Table 1
Authors: R Braham, C Finch, P McCrory
Journal: British Journal of Sports Medicine (2004)

Objective: To ascertain the reasons behind players not participating in a sports safety research project. Methods: During the preseason, 10 Australian football clubs volunteered 23 teams to participate in a protective equipment randomised controlled trial, the Australian Football Injury Prevention Project (AFIPP). All players from these teams were invited to participate. Players who did not agree to participate in AFIPP were surveyed about their reasons for non-involvement. Results: 110 football players (response rate 63.6%) completed the non-responder survey and cited the two main reasons behind non-involvement in the project as “I did not know about the project” (39.4%) and “I was not at training when the research team visited” (36.5%). Conclusions and implications: Preseason may not be the best time for maximal player recruitment in community based sports safety research. Enhanced communication between researchers and players at community level football clubs during the recruitment phase is likely to improve response rates.
Diagnosing Insulin Resistance in the General Population
Authors: Kirsten A. McAuley, Sheila M. Williams, Jim I. Mann, Robert J. Walker, Nick J. Lewis-Barned, Lara A. Temple, Ashley W. Duncan
Journal: Diabetes Care (2001)

OBJECTIVE—Difficulties in measuring insulin sensitivity prevent the identification of insulin-resistant individuals in the general population. Therefore, we compared fasting insulin, homeostasis model assessment (HOMA), insulin-to-glucose ratio, Bennett index, and a score based on weighted combinations of fasting insulin, BMI, and fasting triglycerides with the euglycemic insulin clamp to determine the most appropriate method for assessing insulin resistance in the general population. RESEARCH DESIGN AND METHODS—Family history of diabetes, BMI, blood pressure, waist and hip circumference, fasting lipids, glucose, insulin, liver enzymes, and insulin sensitivity index (ISI) using the euglycemic insulin clamp were obtained for 178 normoglycemic individuals aged 25–68 years. Product-moment correlations were used to examine the association between ISI and various surrogate measurements of insulin sensitivity. Regression models were used to devise weights for each variable and to identify cutoff points for individual components of the score. A bootstrap procedure was used to identify the most useful predictors of ISI. RESULTS—Correlation coefficients between ISI and fasting insulin, HOMA, insulin-to-glucose ratio, and the Bennett index were similar in magnitude. The variables that best predicted insulin sensitivity were fasting insulin and fasting triglycerides. The use of a score based on \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \[Mffm{/}I{\,}{\,}{=}{\,}{\,}exp{[}2.63{\,}{\,}{-}{\,}{\,}0.28ln(insulin){\,}{\,}{-}{\,}{\,}0.31ln(TAG){]}\] \end{document}rather than the use of fasting insulin alone resulted in a higher sensitivity and a maintained specificity when predicting insulin sensitivity. CONCLUSIONS—A weighted combination of two routine laboratory measurements, i.e., fasting insulin and triglycerides, provides a simple means of screening for insulin resistance in the general population.
Improved Staging of Patients With Carcinoid and Islet Cell Tumors With <sup>18</sup>F-Dihydroxy-Phenyl-Alanine and <sup>11</sup>C-5-Hydroxy-Tryptophan Positron Emission Tomography
Authors: Klaas P. Koopmans, Oliver C. Neels, Ido P. Kema, Philip H. Elsinga, Wim J. Sluiter, Koen Vanghillewe, Adrienne H. Brouwers, Pieter L. Jager, Elisabeth G.E. de Vries
Journal: Journal of Clinical Oncology (2008)

To evaluate and compare diagnostic sensitivity of positron emission tomography (PET) scanning in carcinoid and islet cell tumor patients with a serotonin and a catecholamine precursor as tracers.Carcinoid (n = 24) or pancreatic islet cell tumor (n = 23) patients with at least one lesion on conventional imaging including somatostatin receptor scintigraphy (SRS) and computed tomography (CT) scan underwent (11)C-5-hydroxytryptophan ((11)C-5-HTP) PET and 6-[F-18]fluoro-L-dihydroxy-phenylalanine ((18)F-DOPA) PET. PET findings were compared with a composite reference standard derived from all available imaging along with clinical and cytologic/histologic information.In carcinoid tumor patients, per-patient analysis showed sensitivities for (11)C-5-HTP PET, (18)F-DOPA PET, SRS, and CT of 100%, 96%, 86%, 96%, respectively, and in islet cell tumors of 100%, 89%, 78%, 87%, respectively. In carcinoid patients, per-lesion analysis revealed sensitivities for (11)C-5-HTP PET, (11)C-5-HTP PET/CT, (18)F-DOPA PET, (18)F-DOPA PET/CT, SRS, SRS/CT, and CT alone of, respectively, 78%, 89%, 87%, 98%, 49%, 73%, and 63% and in islet cell tumors of 67%, 96%, 41%, 80%, 46%, 77%, and 68%, respectively. In all carcinoid patients (18)F-DOPA PET and (11)C-5-HTP PET detected more lesions than SRS (P < .001). (11)C-5-HTP PET was superior to (18)F-DOPA PET in islet cell tumors (P < .0001). In all cases, CT improved the sensitivity of the nuclear scans.(18)F-DOPA PET/CT is the optimal imaging modality for staging in carcinoid patients and (11)C-5-HTP PET/CT in islet cell tumor patients.
Integrative Analysis of 1q23.3 Copy-Number Gain in Metastatic Urothelial Carcinoma
Authors: Markus Riester, Lillian Werner, Joaquim Bellmunt, Shamini Selvarajah, Elizabeth A. Guancial, Barbara A. Weir, Edward C. Stack, Rachel S. Park, Robert O'Brien, Fabio A.B. Schutz, Toni K. Choueiri, Sabina Signoretti, Josep Lloreta, Luigi Marchionni, Enrique Gallardo, Federico Rojo, Denise I. Garcia, Yvonne Chekaluk, David J. Kwiatkowski, Bernard H. Bochner, William C. Hahn, Azra H. Ligon, Justine A. Barletta, Massimo Loda, David M. Berman, Philip W. Kantoff, Franziska Michor, Jonathan E. Rosenberg
Journal: Clinical Cancer Research (2014)

Metastatic urothelial carcinoma of the bladder is associated with multiple somatic copy-number alterations (SCNAs). We evaluated SCNAs to identify predictors of poor survival in patients with metastatic urothelial carcinoma treated with platinum-based chemotherapy.We obtained overall survival (OS) and array DNA copy-number data from patients with metastatic urothelial carcinoma in two cohorts. Associations between recurrent SCNAs and OS were determined by a Cox proportional hazard model adjusting for performance status and visceral disease. mRNA expression was evaluated for potential candidate genes by NanoString nCounter to identify transcripts from the region that are associated with copy-number gain. In addition, expression data from an independent cohort were used to identify candidate genes.Multiple areas of recurrent significant gains and losses were identified. Gain of 1q23.3 was independently associated with a shortened OS in both cohorts [adjusted HR, 2.96; 95% confidence interval (CI), 1.35-6.48; P = 0.01 and adjusted HR, 5.03; 95% CI, 1.43-17.73; P < 0.001]. The F11R, PFDN2, PPOX, USP21, and DEDD genes, all located on 1q23.3, were closely associated with poor outcome.1q23.3 copy-number gain displayed association with poor survival in two cohorts of metastatic urothelial carcinoma. The identification of the target of this copy-number gain is ongoing, and exploration of this finding in other disease states may be useful for the early identification of patients with poor-risk urothelial carcinoma. Prospective validation of the survival association is necessary to demonstrate clinical relevance.
Phosphotyrosines in the killer cell inhibitory receptor motif of NKB1 are required for negative signaling and for association with protein tyrosine phosphatase 1C.
Authors: A M Fry, L L Lanier, A Weiss
Journal: The Journal of Experimental Medicine (1996)

NKB1 is one member of a growing family of killer cell inhibitory receptors (KIR). It is expressed on natural killer (NK) cells and T cells, and has been shown to inhibit cytolytic functions of these cells upon interacting with its ligand, HLA-B (Bw4). We demonstrate here that the cytoplasmic region of NKB1 is capable of inhibiting T cell activation in Jurkat cells. The tyrosine phosphorylation of the NKB1 KIR consensus motif, YxxL(x)26 YxxL, induces an association with the protein tyrosine phosphatase 1C (PTP1C). Importantly, mutation of both tyrosines in the motif abolished the inhibitory functions of NKB1 and abrogated PTP1C association. Mutational analysis of the individual tyrosines suggest that the membrane proximal tyrosine may play a crucial role in mediating the inhibitory signal. These results demonstrate that KIR can not only inhibit cytolytic activity, but can also negatively regulate T cell receptor activation events that lead to downstream gene activation, and further supports a model that implicates PTP1C as a mediator in the KIR inhibitory signal.
Argon plasma coagulation for successful treatment of early gastric cancer with intramucosal invasion
Authors: T Sagawa
Journal: Gut (2003)

<b>Background:</b> In recent years, there has been an increasing number of cases of early gastric cancer (T1, NX) with intramucosal invasion, which are untreatable by surgical or endoscopic mucosal resection (EMR) because of their high risk. Currently, no adequate treatment is available for such patients. <b>Aim:</b> The main objective of this study was to evaluate whether argon plasma coagulation (APC) is an effective and safe modality for treating early gastric cancer untreatable by surgical resection or EMR. <b>Methods:</b> The study group comprised 20 men and seven women diagnosed with gastric cancer with intramucosal invasion who were considered poor candidates for surgical resection or EMR due to risk factors such as severe cardiac failure or thrombocytopenia. Irradiation conditions for APC treatment were determined using swine gastric mucosa. We used an argon gas flow of 2 l/min at a power setting of 60 W and a maximum irradiation time of 15 s/cm<sup>2</sup>. The follow up period of the 27 patients ranged from 18 to 49 months (median 30 months). <b>Results:</b> All lesions were irradiated easily, including areas anatomically difficult for EMR such as the gastric cardia or the posterior wall of the upper gastric body. In 26 of 27 patients (96%) there was no evidence of recurrence during the follow up period (median 30 months). One patient showed recurrence six months after the treatment but was successfully retreated. No serious complications were found in any of the 27 patients but three patients (11%) experienced a feeling of abdominal fullness. <b>Interpretation:</b> APC is a safe and effective modality for treatment of early gastric cancer with intramucosal invasion untreatable by surgical resection or EMR. However, further observations are necessary to determine the long term prognosis of patients undergoing this treatment.
Portal hypertensive biliopathy
Authors: R. K Dhiman, A. Behera, Y. K Chawla, J. B Dilawari, S. Suri
Journal: Gut (2006)

Extrahepatic portal venous obstruction (EHPVO) is a common cause of portal hypertension in the developing countries, and constitutes up to 40% of all patients with portal hypertension.1,2 EHPVO is a common cause of major upper-gastrointestinal bleeding among children.2–4 The most common presentation in children is well-tolerated variceal bleeding and splenomegaly. In adults, EHPVO is often recognised when evaluating for other disorders or with uncommon presentations such as jaundice, pruritus, acute cholecystitis-like syndrome, ascites and so on, resulting from prolonged portal hypertension.5–7 The portal vein in EHPVO is transformed into a cavernoma, which is a bunch of multiple collateral veins around the obstructed portion of portal vein (fig 1). Marked improvements in the management of variceal bleeding in patients with EHPVO have resulted in an improved survival, thus presenting with unusual symptoms in adulthood.



 Figure 1  
 Splenoportovenogram showing multiple collaterals (portal cavernoma) replacing the portal vein (arrows) in a patient with extrahepatic portal venous obstruction. The splenic vein is normal (arrowheads).



The reasons for EHPVO are obscure in approximately half of the patients. Omphalitis and intra-abdominal sepsis are the common causes in neonates and children. Adults develop EHPVO due to increased blood coagulability, local inflammation, intra-abdominal sepsis, myeloproliferative disorders, underlying cirrhosis, or tumours in the liver, bile ducts or pancreas.7,8,9,10

Gibson et al 11 first reported the relationship between EHPVO and jaundice in 1965. Since then, several cases of obstructive jaundice due to common bile duct (CBD) obstruction caused by cavernomatous transformation of portal vein (portal cavernoma) have been described. Williams et al 12 were the first to report cholangiographic changes caused by choledochal varices. We, for the first time, describe abnormalities on endoscopic retrograde cholangiography (ERC) in a prospective study.13 These abnormalities were similar to those of primary sclerosing cholangitis and …
Emerging Therapeutics for Alzheimer's Disease
Authors: Karen Chiang, Edward H. Koo
Journal: The Annual Review of Pharmacology and Toxicology (2014)

Despite decades of intense research, therapeutics for Alzheimer's disease (AD) are still limited to symptomatic treatments that possess only short-term efficacy. Recently, several large-scale Phase III trials targeting amyloid-β production or clearance have failed to show efficacy, leading to a reexamination of the amyloid hypothesis as well as highlighting the need to explore alternatives in both clinical testing strategies and drug discovery targets. In this review, we discuss therapeutics currently being tested in clinical trials and up-and-coming interventions that have shown promise in animal models, devoting attention to the mechanisms that may underlie their ability to influence disease progression and placing particular emphasis on tau therapeutics.