tbuckley/cabot-search huggingface dataset:
MEDICAL AND SOCIAL FACTORS IN CRIME
Authors: A Stearns
Journal: Annals of Internal Medicine (1943)

Article1 April 1943MEDICAL AND SOCIAL FACTORS IN CRIMEA. WARREN STEARNS, M.D.A. WARREN STEARNS, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-18-4-599 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptWhen a child is born his behavior is almost entirely on a physiological basis. He reacts to various stimuli on a reflex level and draws upon his heritage through past ages for motivation. In other words, his conduct is asocial. His parents begin the task of training forthwith, just as they would in the case of any other animal. This training at first has to do with the regulation of the various functions of the body and with teaching a certain amount of decorum. For a long time it has been recognized that children differ in their capacity to receive...Bibliography1. STEARNS AW: The evolution of punishment, Jr. Crim. Law, 1936, xxvii, 219-230. Google Scholar2. QUINCY J: Report in regard to House of Industry, 1821. Google Scholar3. House of Refuge, First Annual Report. 1826. Google Scholar4. MACONOCHIE A: Report. Google Scholar5. WINES FH: Punishment and reformation, 1895, Crowell, New York, 192-228. Google Scholar6. RUSH B: Medical inquiries and observations upon the diseases of the mind, 1812, Philadelphia, p. 357. Google Scholar7. WOODWARD S: Senate document No. 13—Fourth Annual Report of State Lunatic Asylum. 1836. Google Scholar8. SAMPSON MB: Rationale of crime and its appropriate treatment: being a treatise on criminal jurisprudence considered in relation to cerebral organization, 2nd London edition, 1846, Appleton, New York. Google Scholar9. Same as above. Google Scholar10. STEARNS AW: The personality of criminals, 1931, Beacon Press, Boston. Google Scholar11. GLUECK S: Five hundred criminal careers, 1930, Knopf, New York. Google Scholar12. STEARNS AW: The rôle of the physician in a competitive society, New England Jr. Med., 1941, ccxxiv, 879-890. CrossrefGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Boston, Massachusetts*Received for publication February 13, 1943. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 April 1943Volume 18, Issue 4Page: 599-605KeywordsBehaviorChildrenCrimeMotivationReflexes Issue Published: 1 April 1943 PDF downloadLoading ...
CSPG4 and B7-H3 as prognostic biomarkers in chordoma.
Authors: A. Schoenfeld, G. P. Nielsen, F. Hornicek, Z. Duan, S. Ferrone, J. H. Schwab
Journal: Journal of Clinical Oncology (2010)

10050 Background: Wide surgical margins have been shown to improve survival in chordoma while intralesional margins are associated with recurrence and a worse survival. Aside from margins, no other parameter has proven to be a useful prognostic marker. Since identification of patients with aggressive disease would contribute to optimize therapeutic strategies, this investigation has assessed the value of CSPG4 and B7-H3 as prognostic biomarkers in chordoma. To this end, their expression in primary lesions has been correlated with disease recurrence and patients' survival. Methods: Atissue microArray was constructed from 70 conventional chordoma tumors. Triplicate cores were taken and expression of CSPG4 and B7-H3 was evaluated by immunohistochemistry. Clinical and histologic outcomes and expression of CSPG4 and B7-H3 were compared using the two-tailed Fisher exact test. Cox proportional hazard regression analysis was used to evaluate risk factors for mortality based on expression while controlling for other variables including surgical margin. Results: Of the 70 patients investigated, 50 developed local and 10 developed distant recurrences. Twenty-six patients died of disease. Fifty-eight tumors were postive for B7-H3 and 41 were positive for CSPG4. Nine of the 10 primary tumors associated with metastases expressed CSPG4; CSPG4 expression in primary tumors of patients who developed metastases was significanly (p=0.04) higher than that of the patients who did not. Furthermore CSPG4 expression in primary tumors was associated significantly (76.9%, p=0.004) with a greater risk of dying of disease. The significant (p=0.01) association between CSPG4 and a worse survival was maintained after controlling for surgical margin; the association between CSPG4 and metastases trended toward significance (p=0.08) after controlling for margin. B7-H3 expression was associated with local recurrence, however the association did not reach statistical significance (p=0.09). B7-H3 expression was associated neither with metastases nor with survival. Conclusions: These results indicate that CSPG4 may be a useful prognostic biomarker in chordoma, since its expression was associated with metastases and dying from disease. No significant financial relationships to disclose.
Early response evaluation of sorafenib (SFB) therapy: Use of computed fluorodeoxiglucose positron emission tomography (PET-CT) in advanced hepatocellular carcinoma (HCC).
Authors: M. Lanzuela, R. A. Pazo Cid, J. Lao, J. Fuentes, L. Sarria, C. Horndler, MA Ubieto, T. Puertolas, V. Calderero, A. Anton
Journal: Journal of Clinical Oncology (2010)

e14567 Background: SFB, a multikinase inhibitor of both tumor proliferation and angiogenesis, is the only systemic treatment that increases overall survival in advanced HCC. Radiologic response assessment of HCC to SFB is difficult and RECIST criteria only demonstrates stable disease for most of the cases (Llovet et al N Eng J Med. 2008). The aim of this study is to probe that PET-CT is an early useful tool when evaluating HCC pts on SFB treatment. Methods: Advanced HCC patients (pts) are assessed before starting SFB treatment by PET-CT, diffusion weighted magnetic resonance (DW-MR) and conventional CT. If elevated standardized uptake value (SUV > 2.5) in any HCC lesion pts are reassessed by PET-CT and DW-MR three weeks after beginning SFB, administered at the usual 400mg/bid schedule. Conventional CT assesment is made every 8 weeks. Statistical design included an interim analyses when 20 of the 40 planned accrual pts have been included: study feasibility was granted if basal PET-CT positive scans were found in > 70% of HCC pts. PET-CT SUV response, conventional radiologic assessment, time to progression (TTP) and overall survival (OS) are evaluated. Results: 20 pts included since January 2009. Pts characteristics: male/female 12/8; median age 66.9 (range 59-75); Child-Pugh status A/B/C 8/12/0; cirrhosis ethiology: HBV/HCV/alcohol/other: 4/8/3/3; AFP mean levels 732.0 ng/mL (range 4.9-5338.0). All the 20 pts received at least 6 weeks of SFB. Basal PET-CT positive/negative 17/3 (85% positive); a second PET-CT was performed to the 17 positive pts 3 weeks after begining SFB (range 2-4 weeks) demonstrating SUV reduction in 75% of the pts., correlated with reduced diffusion by DW-MR and stable desease on CT. In PET-CT positive pts pre-SFB median basal SUV value was 4.3 (range 2.8-9.6) and on-SFB median SUV value was 2.2 (range 1.8-4.5). Those pts with > 20% reduction in SUV value compared to pts with increased/< 20% reduction SUV value had a longer median TTP (2.7 vs. 4.2 months) and better OS (5.6 vs 9.6 months). Conclusions: In advanced HCC pts on SFB treatment PET-CT early response assessment is feasible and might be a biomarker with predictive and prognostic value. No significant financial relationships to disclose.
Microfluidic device for circulating tumor cell sorting, characterization, and culture
Authors: A. Saliba, L. Saias, F. Bidard, C. Mathiot, V. Saada, F. Farace, P. Vielh, J. Pierga, J. Viovy
Journal: Journal of Clinical Oncology (2009)

11068 Background: Circulating tumor cell (CTC) analysis is a promising approach to further characterize the tumor biology and the metastatic process, but has immediate clinical applications such as early predictive markers of response to chemotherapy. However, the devices that are used currently for CTC detection have a poor sensitivity. Microfluidic techniques offer new exciting perspectives in the field of cell sorting for CTC analysis. Methods: We propose here a new microfluidic system and strategy allowing the sorting of cells, their study by confoncal fluorescent microscopy and/or their subsequent culture. The core of our system is a self-organized array of superparamagnetic particles in a microchannel, allowing for the formation of a perfectly periodic and robust array. The superparamagnetic particles are coated with specific antibodies against surface antigens, in order to capture cells according to specific biomarkers. This original cell-separation microchip was integrated into a fully automated platform combining state-of-the-art microfluidic technologies, microvalves and nanofluidic pneumatic pumps. Results: Using B and T lymphocytes mixtures as a model biological system, the capture yield was better than 90%, and the specificity better than 97%. Captured cells were fully viable and were cultured in situ in the magnetic array. In clinics, immunophenotyping of circulating malignant B cells was performed using fluorescent confocal microscopy, and was successfully compared to flow cytometry data for each sample. Results on breast cancer cells will be presented at the meeting. Conclusions: This new system is a promising approach for efficient CTC sorting, analysis and culture in a completely integrated manner. No significant financial relationships to disclose.
Assessment of serum concentrations of Dkk1 as potential biomarker for esophageal squamous cell carcinoma
Authors: C. Zer, X. Dong, K. Kernstine, L. Zhong
Journal: Journal of Clinical Oncology (2009)

e15675 Background: Esophageal squamous cell carcinoma (ESCC) is one of the most common fatal cancers worldwide due to the lack of an early disease screening strategy. Identification of diagnostic markers will greatly improve the morbid outcome. Dickkopf 1 (Dkk1) is a secreted antagonist of Wnt signaling pathway, an important pathway in tumorigenesis. The expressions of Dkk1 seem to be tumor-specific: reduced expressions have been seen in colorectal cancer, but elevated levels were reported for hepatoblastomas. In ESCC, the situation is less clear, for both elevation and reduction of Dkk1 were reported. The serum concentrations of Dkk1 have also been shown to be higher in ESCC patients’ sera in one study. In view of the varied outcome from Dkk1 tissue expressions and the scarce reports on Dkk1 serum concentration from ESCC patients, we therefore sought to determine the tissue expression and serum concentrations of Dkk1 as our first step to evaluate the potential of Dkk1 as a diagnostic marker for ESCC. Methods: The expression levels of Dkk1 in ten ESCC tumor and adjacent non-tumor tissues were examined by Western blot. Serum Dkk1 level of 168 samples were quantified in a double-blind fashion by ELISA (Dkk1 Duoset ELISA development kit from R &amp; D Systems, Minneapolis, MN). To ensure that the serum Dkk1 detection was not affected by autoantibodies against Dkk1 present in sera, we also measured serum Dkk1 autoantibody levels by ELISA with modifications to the ELISA kit. Results: Seven out of ten of the tumors showed elevated Dkk1 level, while only two out of ten of the control normal tissue showed elevation. Surprisingly, after decoding of our serum samples into 80 patients and 88 normal controls, we found that Dkk1 level was significantly lower in patient sera (2.99ng/ml) than the normal samples (5.32ng/ml) (p=0.0001; t-test). The measurements were not obscured by the presence of Dkk1 autoantibodies, as they were not different between patient and control samples. Conclusions: Contrary to previous published results, we found Dkk1 is suppressed in patient sera, and thus our result undermines the potential of serum Dkk1 level as a predictive marker for ESCC. Further investigations will be needed to explain the discrepancies between the studies. No significant financial relationships to disclose.
Phase I/II trial of vandetanib in children and adolescents with hereditary medullary thyroid carcinoma
Authors: E. Fox, B. C. Widemann, P. O. Whitcomb, A. Aikin, E. Dombi, M. Lodish, C. A. Stratakis, S. Steinberg, S. A. Wells, F. M. Balis
Journal: Journal of Clinical Oncology (2009)

10014 Background: Mutations in the RET protooncogenecause hereditary medullary thyroid carcinoma (MTC) including Multiple Endocrine Neoplasia (MEN) Type 2A, Type 2B and familial MTC. Vandetanib inhibits VEGFR, EGFR, and RET tyrosine kinases and is active in adults with hereditary MTC. Methods: We are conducting a trial of vandetanib in children and adolescents with RET mutations and MTC. Safety is evaluated at each dose level in adolescents (13–18 years) prior to enrolling children (5–12 years). In the absence of dose limiting toxicity (DLT), intrapatient dose escalation is permitted after cycle 2. To assess bone toxicity, growth plate volume is measured using MRI. Response is monitored using tumor measurements (RECIST), serum biomarkers, calcitonin (CTN), and carcinoembryonic antigen (CEA). Results: Five adolescents and 2 children were enrolled at the 100 mg/m 2 dose level, 3 adolescents were dose escalated to 150 mg/m 2 . Six have MEN2B (M918T RET mutation). Median (range) baseline CTN was 12,200 pg/mL (2,300–67,000) and CEA was 104 mcg/L (5–325). Dose limiting diarrhea was observed in 1/5 adolescents at the 100 mg/m 2 and 1/3 adolescents escalated to 150 mg/m 2 . No DLTs were observed in children receiving 100 mg/m 2 . Non-DLT included elevated TSH (n = 6), rash (n = 5), anorexia (n = 3), diarrhea (n = 2), hypertension (n = 1), and fatigue (n = 1). Median (range) percent change in growth plate volume during therapy was -18% (-44% to + 50%). All patients had linear growth during therapy. Serum CTN and CEA decreased by ≥ 50% in 6/7 and 2/7 patients, respectively. Tumor size decreased in 6/6 patients with M918T RET mutations; 2 achieved RECIST partial response after 6 and 12 cycles. Conclusions: Preliminary results suggest that vandetanib has activity in children and adolescents with MEN2B associated MTC. Vandetanib 100 mg/m 2 was well tolerated. Linear growth was not impaired. [Table: see text]
AB0139 Activation of Dickkopf-1 and Focal Adhesion Kinase Pathway by Tumor Necrosis Factor-Alpha Enhanced Migration of Fibroblast-Like Synoviocytes in Rheumatoid Arthritis
Authors: S.-K. Kim, J.-Y. Choe
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> The migration of fibroblast-like synoviocytes (FLS) has been recognized as a unique feature in rheumatoid arthritis (RA). <h3>Objectives</h3> This study investigated the role of dickkopf-1 (DKK-1) and integrin-related focal adhesion kinase (FAK) on the cell migration of fibroblast-like synoviocytes (FLS) through the regulation of β-catenin in RA. <h3>Methods</h3> The activation of migration were preformed by wound scratching assays. The expression of Wnt/β-catenin and FAK signaling molecules was determined by western blot. Expression of integrin αv, laminin, fibronectin, E-cadherin, integrins, MMP-8, and MMP-13 was measured by real-time quantitative RT-PCR. The DKK-1 morphology was observed by fluorescence microscopy. The inhibitory effects of TNF-α were employed by small interfering RNA transfection into cells. <h3>Results</h3> More enhanced DKK-1 and TNF-α expression in migrating RA FLS were noted than those in OA FLS and/or stationary FLS. Migrating FLS induced FAK, p-JNK, paxillin, and cdc42 expression, but attenuated cytosolic β-catenin expression. WAY-262611 markedly inhibited cell migration in RA FLS through accumulation of cytosolic β-catenin and suppression of FAK-related signaling pathway. TNF-α enhanced DKK-1, integrin αv, fibronectin, laminin, and MMP-13 expression, which were markedly reduced by WAY-262611 treated with FLS. Increased expression of integrin-related FAK and its downstream molecules such as paxillin, JNK, and cdc42 in migrating FLS was suppressed by blocking TNF-α using RLS trasnfected with siRNA TNF-α. TNF-α suppressed cytosolic β-catenin and E-cadherin expression in time-dependent manner. <h3>Conclusions</h3> This study demonstrated that enhanced expression of DKK-1 and activation of integrin-related FAK signal pathway stimulated by TNF-α induced dissociation of β-catenin and E-cadherin, then resulting in promotion of RA FLS migration. <h3>References</h3> Neumann E, et al. Trends Mol Med 2010;16:458-68. Müller-Ladner U, et al. Am J Pathol 1996;149:1607-15. Cadigan KM, et al. Genes Dev 1997;11:3286-305. Koch S, et al. Mol Biol Cell 2009;20:4816-25. Kuang HB, et al. Front Biosci 2009;14:2212-20. <h3>Disclosure of Interest</h3> None declared
Inflammation-Induced CCR7 Oligomers Form Scaffolds to Integrate Distinct Signaling Pathways for Efficient Cell Migration
Authors: Mark A. Hauser, Karin Schaeuble, Ilona Kindinger, Daniela Impellizzieri, Wolfgang A. Krueger, Christof R. Hauck, Onur Boyman, Daniel F. Legler
Journal: Immunity (2016)
Preoperative chemoradiotherapy regimen with capecitabine and bevacizumab in locally advanced rectal cancer: A feasibility study of the Dutch Colorectal Cancer Group (DCCG)
Authors: C. A. Marijnen, H. Rutten, H. de Wilt, M. E. Tesselaar, J. Nuyttens, J. Remmelzwaal, C. J. Punt, H. Martijn, G. A. Hospers, A. Cats
Journal: Journal of Clinical Oncology (2008)

15040 Background: Radiotherapy (RT) combined with 5FU and bevacizumab seems a promising combination for locally advanced rectal cancer, but little data are available regarding toxicity and surgical complications. This multicenter study tests the feasibility of the combination of RT, capecitabine and bevacizumab in rectal cancer patients. Method: 60 patients with a rectal adenocarcinoma with a threatened or involved circumferential resection margin (CRM) will be included. Treatment consists of radiotherapy (50 Gy/25), capecitabine 825 mg/m2 bid and bevacizumab 5 mg /m2 iv on day -14, 1, 15 and 29, with surgery 6–10 weeks thereafter. An interim analysis was scheduled after the inclusion of 15 patients with abdominoperineal resection (APR)/Hartmann procedures. In general, CTC toxicity criteria were used, for local skin toxicity RTOG criteria were used. Results: So far, 23 patients (12 cT3, 11 cT4 tumors) have been entered: 12 APR, 3 Hartmann procedures and 7 low anterior resections (LAR). One patient died before surgery. During chemoradiotherapy (CRT), 7 grade 3 toxicities (4 skin, 2 diarrhea, 1 tenesmi) and one grade 4 toxicity (anal mucositis) were reported. One patient developed an enteritis with diffuse uncontrollable bleeding at the end of the CRT. This patient died before rectal surgery. Two small bowel perforations occurred, with one occurring 70 days after the last administration of bevacizumab. A third patient had an asymptomatic rectal wall perforation at the site of the primary tumor. Surgical complications consisted of one perineal dehiscence, one rectovaginal fistula after a stapling failure and oneperoperative bleeding (5500 cc). Postoperatively, one patient developed a pulmonary embolism. The CRM was negative in 20/22 operated patients. Downstaging of the T-stage was observed in 18/21 patients. Of those, two patients had a complete pathological response, whereas 9 patients had a ypT0–2 tumor. Conclusions: These results indicate that the combination of radiotherapy, capecitabine and bevacizumab is very effective. The observed toxicity pattern warrants further investigation of the relationship between radiation-induced enteritis and small bowel complications. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Roche
The effects of indomethacin on the refractory period to hypertonic saline-induced bronchoconstriction
Authors: RJ Hawksworth, SP O'Hickey, TH Lee
Journal: European Respiratory Journal (1992)

The purpose of this study was to determine the effect of pretreatment with indomethacin on the refractory period to hypertonic saline-induced bronchoconstriction. In a double-blind, placebo-controlled, randomized trial nine asthmatic subjects underwent two hypertonic saline challenges, 60 min apart, on a control day and after premedication with indomethacin 50 mg or matching placebo, twice daily for three days. Premedication with indomethacin did not change airway responsiveness to the initial hypertonic saline challenge. The mean maximal % fall in specific airway conductance (sGaw) was 40.3, 44.1 and 47.6% on the control, placebo and indomethacin days, respectively. Subjects were significantly less responsive to the second hypertonic challenge as compared to the initial challenge on all three study days. There was a variable effect of indomethacin pretreatment on the refractory period. Five subjects lost their refractory period after indomethacin, when the variability of the test was taken into account. This suggests that there may be contributory mechanisms to the refractory period other than the release of protective prostanoid metabolites.
Genotype-phenotype correlations of amyotrophic lateral sclerosis
Authors: Hong-Fu Li, Zhi-Ying Wu
Journal: Translational Neurodegeneration (2016)

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease characterized by progressive neuronal loss and degeneration of upper motor neuron (UMN) and lower motor neuron (LMN). The clinical presentations of ALS are heterogeneous and there is no single test or procedure to establish the diagnosis of ALS. Most cases are diagnosed based on symptoms, physical signs, progression, EMG, and tests to exclude the overlapping conditions. Familial ALS represents about 5 ~ 10 % of ALS cases, whereas the vast majority of patients are sporadic. To date, more than 20 causative genes have been identified in hereditary ALS. Detecting the pathogenic mutations or risk variants for each ALS individual is challenging. However, ALS patients carrying some specific mutations or variant may exhibit subtly distinct clinical features. Unraveling the respective genotype-phenotype correlation has important implications for the genetic explanations. In this review, we will delineate the clinical features of ALS, outline the major ALS-related genes, and summarize the possible genotype-phenotype correlations of ALS.
Lung positron emission tomography with FDG in patients with haematological malignancies and acute respiratory failure
Authors: Marc Pineton De Chambrun, Virginie Lemiale, Élie Azoulay
Journal: European Respiratory Journal (2015)

Diagnostic strategy in haematology patients with pulmonary infiltrates relies on different approaches [1, 2]. Over the past decade, the use of 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) has been widely used to detect inflammatory and malignant processes, to evaluate the extent of a malignancy, and to ascertain response to therapy. Hot et al . [3] reported diagnostic contribution of FDG-PET in patient with invasive fungal infection. More recently, Veronesi et al . [4] reported PET findings in the diagnostic work-up of screening-detected lung nodules. PET-computed tomography (CT) was highly sensitive for the differential diagnosis of indeterminate nodules detected at baseline, nodules ≥15 mm and solid nodules [4]. However, FDG-PET has never been evaluated in unselected patients with acute respiratory failure that complicates haematological malignancies. Lung FDG-PET may help to identify aetiology of pulmonary infiltrates in immunocompromised patients <http://ow.ly/S24gC>