tbuckley/cabot-search huggingface dataset:
Monitoring marketing of infant formula feeds
Authors: M. Sachs
Journal: BMJ (2003)

Editor—Waterson and Tumwine assert that governments should accept promotion and protection of breast feeding as critical for improving child health.1 In May 2002 the World Health Assembly produced its strategy for infant and young child feeding.2 The World Health Organization's international code of marketing of breast milk substitutes3 and subsequent relevant assembly resolutions are integral to this strategy, which is intended as a model for all governments to adapt and adopt as national policy.

In the United Kingdom there is no indication that the government is considering this strategy or intends to commit to a comprehensive national policy, including the implied collection and evaluation of information.2 Currently only some provisions of the WHO code and World Health Assembly resolutions are enacted in UK legislation; no formal monitoring has been undertaken; legal mechanisms for enforcement have proved cumbersome. Since the United Kingdom performs poorly in terms of breastfeeding rates in comparison with other European countries there is no room for complacency (R Saadev, Department of Health conference on barriers to breast feeding, London, 2002).

If the United Kingdom were to commit to a national policy on feeding infants and young children it would help protect child health in the United Kingdom. In addition, if full collaboration of all concerned government agencies were implemented effectively, aid to low income countries could include capacity building so that countries such as Togo and Burkina Faso would have the means to monitor the protection of their children's health. Currently monitoring is all too often left to small non-governmental groups operating on shoestring budgets. Let us take heed of the warning from west Africa and act now in the United Kingdom to contribute nationally to global child health.4
Relief workers need professionalism
Authors: L. Dillner
Journal: BMJ (1995)

Relief workers are more affected by organisational issues and security problems than by witnessing suffering, says a report published by the Overseas Development Administration in London. The report, based on a questionnaire survey of 200 expatriate aid workers, says that recruitment to relief work is often casual, management in the field is poor, and workers are not always fully debriefed.

“The whole framework for intervention has changed, with more agencies now working in the middle of conflict zones,” says Jo Macrae, a research fellow at the Overseas Development Institute. “There were 135 non-governmental agencies working in Rwanda. Ten years ago aid workers would have been in refugee camps …
Correlation of statin use and duration with increased survival in hormone refractory prostate cancer
Authors: N. T. Rich, B. J. Smith, D. A. Vaena
Journal: Journal of Clinical Oncology (2006)

14617 Background: Prior studies associated statin use with prevention and reduced progression of prostate cancer. (Platz et al, 96 th AACR abst. 4374). However, the effects of statins in hormone refractory prostate cancer (HRPC) are unknown. We evaluated the impact of statins on survival of HRPC patients by comparing actual survival data with predicted survival using the Halabi nomogram (JCO 21:(7);1232). Methods: Using the Iowa City VA (ICVA) prescription database since 2001 along with chart review, we identified 28 consecutive patients who were prescribed statins when they had HRPC. Survival information, duration of statin use while HRPC, and Halabi nomogram variables were collected (Hb, PS, Alk Phos, Gleason, PSA). An LDH value of 90 U/L (low-normal at ICVA) was used for all patients, since LDH values were not available. Log-rank and and Cox regression analyses were performed. The outcome of interest was overall survival. Patients alive at last follow-up were censored. Statin use was treated as a time-dependent covariate in the regression analysis, and subject-specific predicted survival from the Halabi nomogram as another covariate. Results: 17 patients were alive and 11 had died. Median duration of follow-up for patients alive was 23 months. The observed vs. nomogram-predicted estimated median survivals were 36 vs. 17 months, respectively. Study patients significantly outlived their nomogram-predicted survival (p = 0.0004). Four patients had negative bone scans. 12 patients outlived their nomogram, 8 died before, and 8 were indeterminate (censored prior to their Halabi-predicted survival). Risk of death decreased with greater length of statin use (p = 0.02). When covariates for Halabi nomogram and statin use were both included in a multivariate regression model, neither was statistically significant, although similar point estimates for the relative risks were obtained. Conclusions: Statin use, and longer duration of use, significantly improved survival of HRPC patients in univariate analysis. The sample size limits the multivariate analysis. Evaluation of a time-dependent statin effect in HRPC could be considered in larger studies. No significant financial relationships to disclose.
Risk of secondary malignancy in patients with testicular cancer who have received radiation therapy.
Authors: D. Lewinshtein, C. R. Porter
Journal: Journal of Clinical Oncology (2010)

4537 Background: Patients with testicular cancer undergo therapeutic regimens that are known to have deleterious long-term effects. We hypothesized that these patients may have an increased baseline risk for secondary malignancies, and that radiotherapy may further increase their risk of developing certain cancers. We explored the rates of secondary bladder cancer, leukemia and lymphoma in testicular cancer patients. Methods: We retrospectively searched the SEER database for all patients diagnosed with primary testicular cancer between 1973 and 2006. We then calculated rates of secondary leukemia, lymphoma and bladder cancer via ICD-O-3 codes. Secondary malignancies were included only if they were diagnosed after the testicular cancer. We calculated secondary cancer rates in the overall cohort and in those patients that received radiotherapy. Results: Between 1973 and 2006, there were 20,300 patients diagnosed with a testicular cancer. The median age of diagnosis was 33 years. They were followed for a total of 285,077 person-years, and their median follow up was 13.0 years. Of all patients with testicular cancer, 8590 (43%) received some form of radiation therapy. Of all patients, 139 developed lymphoma or leukemia, and 99 developed bladder cancer. Of those patients who received radiotherapy, 76 developed lymphoma or leukemia, and 56 developed bladder cancer. The calculated rates of lymphoma-leukemia were 48.9 and 61.01 cases per 100, 000 persons per year, for all testicular cancer patients and those that received radiotherapy, respectively. These rates were 15.3% and 44% higher than national cancer institute published rates. The calculated rates of bladder cancer were 34.7 and 44.0 cases per 100, 000 persons per year, for all testicular cancer patients and those that received radiotherapy, respectively. These rates were 6.5% lower and 19% higher than national averages. Conclusions: In our analysis, patients with testicular cancer had an increased rate of leukemia and lymphoma, which was augmented by radiotherapy. Thus, patients should counseled accordingly as to the risks of radiotherapy, and should be closely followed for life given the potential development of secondary malignancy. No significant financial relationships to disclose.
Production of Adenocarcinomas of the Small Intestines of Wistar Rats Fed Panfuran-S Containing 3-Di(hydroxymethyl)amino-6-(5-nitro-2-furylethenyl)-1,2,4-triazine 2
Authors: Yoichi Konishi, Ayumi Denda, Seiichi Takahashi, Shoji Inui, Yoshinari Aoki
Journal: JNCI Journal of the National Cancer Institute (1978)

Panfuran-S in the diet produced a high incidence of invasive and metastatic adenocarcinomas of the duodenum and the jejunum in outbred Wistar rats. Depressed growth and incidence of cancer production were dose-dependent. Adenocarcinomas of the duodenum were present in 2 of 18 (11%) rats that received 1,750 ppm 3-di(hydroxymethyl)amino-6-(5-nitro-2-furylethenyl)-1,2,4-triazine (DHNT) in the diet and in 11 of 19 (58%) rats that received 3,500 ppm DHNT. Adenocarcinomas of the jejunum were present in 10 of 18 (56%) and 16 of 19 (84%) rats that received 1,750 and 3,500 ppm DHNT, respectively, for 35-37 weeks. The only other tumors observed were squamous cell papillomas of the forestomach. Histologically, most of the adenocarcinomas appeared tubular or papillary and were similar to adenocarcinomas in the small intestine of man and also to human intestinal-type adenocarcinoma of the stomach. This system provided a useful experimental model for the study of the pathogenesis of carcinoma of the small intestine.
Randomized phase II study of mogamulizumab (KW-0761) plus VCAP-AMP-VECP (mLSG15) versus mLSG15 alone for newly diagnosed aggressive adult T-cell leukemia-lymphoma (ATL).
Authors: Tatsuro Jo, Takashi Ishida, Shigeki Takemoto, Hitoshi Suzushima, KImiharu Uozumi, Kazuhito Yamamoto, Naokuni Uike, Yoshio Saburi, Kisato Nosaka, Atae Utsunomiya, Kensei Tobinai, Hiroshi Fujiwara, Kenji Ishitsuka, Shinichiro Yoshida, Naoya Taira, Yukiyoshi Moriuchi, Kazunori Imada, Toshihiro Miyamoto, Masao Tomonaga, Ryuzo Ueda
Journal: Journal of Clinical Oncology (2013)

8506 Background: Mogamulizumab (Moga), a defucosylated humanized anti-CCR4 antibody, was approved for the treatment of relapsed/refractory ATL in Japan in 2012. This multicenter, randomized, phase II trial was conducted to examine the efficacy of the combination of Moga with standard chemotherapy for untreated aggressive ATL. Methods: Previously untreated patients (pts) with CCR4-positive ATL were randomly assigned to receive mLSG15 plus Moga (arm A) or mLSG15 alone (arm B). The primary endpoint was CR rate (%CR), and secondary endpoints included ORR, PFS, OS and safety. Pts received 4 courses of mLSG15 regimen, with or without a total of 8 doses of Moga (1.0 mg/kg) once every 2 weeks. The planned sample size, 22 pts per arm, provided a probability of 80% that %CR in arm A would have larger %CR when true %CR for arm A is 15% better than that for arm B. Results: Of 54 pts randomized, 53 were treated (arm A: 29; arm B: 24). Male/female ratio was 53/47%, median age was 63 (37-81), and subtype was acute/lymphoma/unfavorable chronic, 70/25/6%. %CR and ORR in arms A and B was 52% (95%CI [CI]; 33, 71) vs. 33% (CI; 16, 55) and 86% (CI; 63, 96) vs. 75% (CI; 53, 90), respectively. The results in arm B were similar to the previously reported %CR of 40% and ORR of 72% with mLSG15 (Tsukasaki et al, JCO 2007). ORR according to the disease subtype, in arms A and B, was 55% vs. 29% for acute, 50% vs. 43% for lymphoma and 33% vs. 0% for unfavorable chronic. Median PFS was 259 days (CI; 197, -) for arm A and 192 days (CI; 147, -) for arm B. Median OS was not reached in both arms. The most common treatment-related AEs in each arm were neutropenia (100%, 96%), thrombocytopenia (100%, 96%), leukopenia (100%, 92%), lymphocytopenia (97%, 96%), anemia (97%, 92%) and febrile neutropenia (90%, 88%). In arm A, skin disorders were more frequent but manageable, and no serious skin disorder like Stevens-Johnson syndrome was observed. There was one treatment-related death, which was not related to Moga. Conclusions: The combination of Moga with mLSG15 was well tolerated and the study met its primary endpoint. These results suggest that Moga with mLSG15 is a rational treatment option for newly diagnosed aggressive ATL. Clinical trial information: NCT01173887.
Found in Translation: A Type 1 Diabetes Genetic Risk Score Applied to Clinical Diagnosis
Authors: Jose C. Florez
Journal: Diabetes Care (2016)

We are entering a new era in which the explosion of genomic and biological information across multiple developmental and metabolic states is poised to transform the practice of medicine (1). It is now possible to center scientific investigation in the key model organism, the human, and to deploy modern technologies to acquire an unprecedented trove of biological data at multiple time points in the life of an individual (2).

The genomic revolution illustrates how big data sets can begin to yield biological and clinical insight. Concurrent advances in genotyping and sequencing technologies, in our understanding of human genetic variation, and in the statistical methodologies needed to interpret genetic findings have all led to a meteoric expansion in genetic knowledge (3). Meta-analyses of genome-wide association studies (GWAS) and ongoing comprehensive sequencing experiments are yielding a plethora of genetic associations from an agnostic vantage point, which can open unsuspected windows into the pathophysiology of metabolic phenotypes, including type 1 (4) and type 2 (5,6) diabetes.

However, whether this emerging body of knowledge will deepen our understanding of health and disease and lead to improved outcomes in public health remains to be seen. A frequent criticism of large-scale genomic studies is that so far they have failed to deliver on the hyped hopes that the human genome would usher in personalized medicine. Given the empirical observation that most genetic effects for complex phenotypes are modest, skeptics rightly argue that their utility for individualized prediction has not been proven, and they jump to conclude that the substantial public investment in resources, effort, and human capital in this line of investigation has been a wash.

Geneticists may counter that skeptics seem to ignore how genetic studies have illuminated pathophysiological mechanisms that remained obscure, such as the seminal involvement of neuronal circuits in …
Pretreatment serum TIMP-1 levels and survival in advanced pancreatic cancer
Authors: R. Vargas, V. Shrivastava, K. Leitzel, S. M. Ali, W. Carney, P. Hamer, S. Brown-Shimer, R. Linnartz, B. Mietlowski, A. Lipton
Journal: Journal of Clinical Oncology (2009)

e15568 Background: Tissue inhibitor of metalloproteinase-1 (TIMP-1) has been shown to have diverse multifunctional roles in tumorigenesis such as inhibition of the catalytic activity of MMPs, growth promotion, inhibition of apoptosis and regulation of angiogenesis. Elevated TIMP-1 has been associated with an unfavorable prognosis in many cancers including breast, colorectal, gastric, head and neck, lung, and lymphoma. VEGF is also intimately associated with angiogenesis. Methods: This study determined serum TIMP-1 and VEGF levels in a phase III clinical trial of 157 patients with advanced pancreatic cancer. ELISAs for TIMP-1 and VEGF (Oncogene Science / Siemens HealthCare Diagnostics, Cambridge, MA) were employed to measure pretreatment serum TIMP-1 levels in 157 pancreatic cancer patients enrolled in a randomized, double-blind, placebo-controlled phase III trial. Statistical analysis was performed with TIMP-1 and VEGF on a continuous and cutpoint basis. Serum biomarker levels were then correlated with patient survival using Kaplan -Meier life table analysis. Results: Serum TIMP-1 levels in 157 pancreatic patients had a median of 409.9 ng/mL, and ranged from 144 to 1078 ng/mL. Patients with higher serum TIMP-1 had significantly shorter survival on a continuous basis (p = 0.001), on quartile analysis (p = 0.004), and on a dichotomous cutpoint analysis of upper 25 % vs lower 75 % (median survival 101 days vs. 197 days)(p&lt; 0.001). Serum VEGF level was not associated with survival on a continuous (p = 0.57) or cutpoint analysis (p= 0.93). Conclusions: Pancreatic cancer patients with higher serum TIMP-1 levels had significantly shorter overall survival. Serum TIMP-1 level should be evaluated as a predictive factor for response to novel treatment regimens. [Table: see text]
Mitochondrial DNA evolution in the genus Equus.
Authors: M George, O A Ryder
Journal: Molecular Biology and Evolution (1986)

Employing mitochondrial DNA (mtDNA) restriction-endonuclease maps as the basis of comparison, we have investigated the evolutionary affinities of the seven species generally recognized as the genus Equus. Individual species' cleavage maps contained an average of 60 cleavage sites for 16 enzymes, of which 29 were invariant for all species. Based on an average divergence rate of 2%/Myr, the variation between species supports a divergence of extant lineages from a common ancestor approximately 3.9 Myr before the present. Comparisons of cleavage maps between Equus przewalskii (Mongolian wild horse) and E. caballus (domestic horse) yielded estimates of nucleotide sequence divergence ranging from 0.27% to 0.41%. This range was due to intraspecific variation, which was noted only for E. caballus. For pairwise comparisons within this family, estimates of sequence divergence ranged from 0% (E. hemionus onager vs. E. h. kulan) to 7.8% (E. przewalskii vs. E. h. onager). Trees constructed according to the parsimony principle, on the basis of 31 phylogenetically informative restriction sites, indicate that the three extant zebra species represent a monophyletic group with E. grevyi and E. burchelli antiquorum diverging most recently. The phylogenetic relationships of E. africanus and E. hemionus remain enigmatic on the basis of the mtDNA analysis, although a recent divergence is unsupported.
Calling for ‘inguinal disruption’ to be the term of choice for disorders of the inguinal ring: connecting Manchester and Doha
Authors: Aali J Sheen, Saurabh Jamdar, Waqar Bhatti
Journal: British Journal of Sports Medicine (2015)

The Doha statement has been an enormous and challenging piece of work, bringing together world leaders in the field of groin-related injuries to try and best classify the possible cause(s) of groin-related pain.1 Doha does build on the recent searches in agreement with this topic, but with scrutiny of the entire groin. Manchester's was the first consensus statement attempting to define a popular nomenclature for groin pain specifically attributed to an exclusively inguinal pathology.2 The term ‘inguinal disruption’ has now been successfully introduced into the language of clinicians and physiotherapists.2

Could it be …
Phase II experience with MDX-1106 (Ono-4538), an anti-PD-1 monoclonal antibody, in patients with selected refractory or relapsed malignancies
Authors: J. R. Brahmer, S. L. Topalian, J. Powderly, I. Wollner, J. Picus, C. G. Drake, E. Stankevich, A. Korman, D. Pardoll, I. Lowy
Journal: Journal of Clinical Oncology (2009)

3018 Background: Programmed death-1 (PD-1), an inhibitory receptor expressed on activated T cells, may suppress antitumor immunity. This expansion cohort in a phase I/II trial of MDX-1106, a fully human IgG4 antibody blocking PD-1, sought to further evaluate the safety and activity of the 10 mg/kg dose. Other objectives included evaluation of pharmacokinetics (PK) and immunological effects. Methods: Patients (pts) with treatment refractory metastatic non-small cell lung cancer (NSCLC), renal cell carcinoma (RCC), colon cancer (CC), melanoma (MEL), or prostate cancer (CRPC), and no history of autoimmune disease received a single infusion of MDX-1106 at 10 mg/kg. Disease status was evaluated at week (wk) 8 by RECIST criteria. Pts with stable disease or lesional responses could receive additional MDX-1106 at wks 12 and 16. Those with PR/CR were observed without retreatment. Results: 21 pts (5 CC, 2 NSCLC, 8 MEL, 5 HRPC, 1 RCC) were treated from 10/07 to present, and 6 were retreated. No MDX-1106 related SAEs occurred. One pt developed arthritic symptoms requiring treatment, and 2 pts had asymptomatic TSH elevation. One pt with RCC had a PR after 3 doses, lasting 5+ months (mo). Lesional regressions (“mixed response”) were seen in 2 MEL pts; to date, one has received 7 doses of MDX-1106 over 15 mo without serious toxicity. Biopsy of a regressing MEL lymph node metastasis showed a moderately increased and selective CD8+ T cell infiltrate post treatment. The median serum t 1/2 of MDX-1106 was 20.6 days, which was roughly 50% longer than observed for lower doses. There was no evidence of immunogenicity based on HAHA development. Interestingly, in contrast to PK results, flow cytometric analysis demonstrated sustained occupancy of 60–80% PD-1 molecules on T cells for at least 3 mo following a single dose. Analyses of circulating lymphocyte subsets and tumor B7-H1 expression are in progress. Conclusions: Intermittent dosing of MDX-1106 at 10 mg/kg demonstrated clinical activity against RCC and MEL without serious toxicity. Therapy with MDX-1106 to enhance endogenous antitumor immunity, either alone or combined with other immunological therapies, warrants further study. [Table: see text]
Relationship Between Leukemia Antigens and Stimulation in Mixed Leukocyte Culture: Brief Communication2
Authors: Gerhard Opelz, Robert P. Gale, John D. McClelland
Journal: JNCI Journal of the National Cancer Institute (1977)

Journal Article Relationship Between Leukemia Antigens and Stimulation in Mixed Leukocyte Culture: Brief Communication Get access Gerhard Opelz, Gerhard Opelz Search for other works by this author on: Oxford Academic PubMed Google Scholar Robert P. Gale, Robert P. Gale Search for other works by this author on: Oxford Academic PubMed Google Scholar John D. McClelland John D. McClelland Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 59, Issue 1, July 1977, Pages 95–98, https://doi.org/10.1093/jnci/59.1.95 Published: 01 July 1977 Article history Received: 22 November 1976 Accepted: 25 January 1977 Published: 01 July 1977
Abstract 19569: Inhibition of Cardiac Actin-Myosin Interaction by Blebbistatin Delays Onset of Ventricular Fibrillation during Myocardial Ischemia
Authors: Amanda S Hatcher, Hugh Clements-Jewery
Journal: Circulation (2012)

Sudden cardiac death in the context of coronary heart disease is most commonly the result of the occurrence of ventricular fibrillation (VF) following a new episode of myocardial ischemia. The electrophysiological disturbances that create a substrate for the development of VF in myocardial ischemia can be traced back to depletion of cellular ATP resulting from ATP consumption outstripping supply. Reducing cardiac ATP consumption may thus delay or inhibit the development of VF in ischemia. Therefore, we determined the effect of blebbistatin, a selective inhibitor of contraction that will reduce ATP consumption via reducing cardiac work, on the incidence and time of onset of ventricular fibrillation (VF) in an established model of regional myocardial ischemia. Isolated male rat hearts (n=12 per group) were randomized to one of 4 groups: control (vehicle 0.01% v/v), 0.1µM blebbistatin, 1µM blebbistatin, or 10µM blebbistatin. The ECG and left ventricular developed pressure (LVDP) were recorded in each heart. Hearts were perfused with test solution for 15 min, after which regional myocardial ischemia was induced by tightening a snare occluder placed around the left main coronary artery. Ischemia was maintained for 30 min. As expected, prior to myocardial ischemia, blebbistatin reduced LVDP (p&gt;0.05 vs control), abolishing it at the 1µM and 10µM concentrations. Compared to control, the incidence of VF during ischemia was not affected at blebbistatin concentrations of 0.1µM and 1µM (83% and 92% respectively vs 83% in controls) and was reduced only as a trend with 10µM blebbistatin (67%; p&lt;0.05). However, there was a concentration-dependent prolongation in the mean time to onset of VF with blebbistatin, which was significantly longer than the mean time to VF onset in controls at a concentration of 10µM (1367±113s vs 924±80s; p&lt;0.05). This effect of blebbistatin was associated with a trend to increased ATP content in myocardial tissue samples taken from the ischemic zone as measured by luciferase luminescence assay. In conclusion, a reduction in cardiac work by inhibition of the cardiac contractile machinery can delay the onset of VF during myocardial ischemia, most likely as a consequence of delaying the depletion of myocardial ATP.