The democratic origins of the term "group analysis": Karl Mannheim's "third way" for psychoanalysis and social science.

It is well known that Foulkes acknowledged Karl Mannheim as the first to use the term ‘group analysis’. However, Mannheim’s work is otherwise not well known. This article examines the foundations of Mannheim’s sociological interest in groups using the Frankfurt School (1929–1933) as a start point through to the brief correspondence of 1945 between Mannheim and Foulkes (previously unpublished). It is argued that there is close conjunction between Mannheim’s and Foulkes’s revision of clinical psychoanalysis along sociological lines. Current renderings of the Frankfurt School tradition pay almost exclusive attention to the American connection (Herbert Marcuse, Eric Fromm, Theodor Adorno and Max Horkheimer) overlooking the contribution of the English connection through the work of Mannheim and Foulkes

The development of ICP-MS methods for the study of biomedical problems particularly those involving nucleic acids

Inductively coupled plasma mass spectrometry (ICP-MS) is a well established and versatile technique for the elemental analysis of a wide spectrum of samples. For a majority of the elements that can be analysed by ICP-MS limits of detection in the order of sub ng 1 1 levels can be attained. However, a number of these elements have problems associated with them that lead to a restriction of the limits of detection that can be achieved. Phosphorus and Sulphur are two such elements that exhibit poorer limits of detection, the improvement of which would be highly desirable to the ICPMS analyst. Six methods for the measurement of 31p and 32S isotopes have been developed with the aim of avoiding the spectroscopic interferences at the native m/z ratios of 31 and 32 respectively. These approaches have utilised a hexapole collision cell, a 'cold/cool plasma' and an experimental ICP torch bonnet. Via the collision cell and 'cold/cool plasma' approaches the isotopes of interest were either converted to different species for successful measurement at an alternative m/z ratio or interfering species were removed allowing measurement at the native m/z. Limits of detection achieved by these approaches were comparable with those quoted in the literature and by ICP-MS instrument manufacturers. The approach using the torch bonnet was not successful in attenuating spectroscopic interferences; however, it did show potential for continuing as an area of research. The development of these six methods is discussed in Chapter 2. As an application of the successful methods developed for the measurement Of 31p and 328 isotopes, DNA (and its associated components) was selected for study as this biomolecule is comprised of approximately IO % phosphorus. DNA in solution was successfully quantified by these methods and DNA components, studied during polymerase chain reaction processes and in single nucleotide polymorphisms, were qualified. The application of these methods to the study of DNA and its components is discussed in Chapter 3. As part of a collaboration between the Loughborough University Atomic Spectroscopy Research Group and the Cancer Biomarkers and Prevention Group at the University of Leicester, ICP-MS was employed in the investigation of the interactions between two Pt based anti-cancer drugs (cisplatin and oxaliplatin) and their biological target DNA. For this collaboration, DNA was the interest common to both groups. The interaction of each of these drugs with known quantities of DNA was measured by ICP-MS and binding constant data was calculated for use as the basis of a clinical test for drug efficacy in cancer patients. The binding constant data showed that the interaction between drug and target is particularly inefficient. This area of research is discussed in Chapter 4. The potential for ICP-MS interface modification was also explored. Two modified designs are discussed that may prove to be advantageous for the transport of ions between the atmospheric pressure conditions of the ICP ion source and the vacuum conditions of the mass spectrometer. One of these designs was successfully manufactured and produced positive data. Research into this design is being furthered by the Thermo Electron Corporation, the discussion of which is in Chapter 5. A further collaboration was established with both the Biomaterials-related Infection Group of the School of Medical and Surgical Sciences and the Polymer Group of the School of Mechanical, Materials and Manufacturing Engineering at the University of Nottingham. Here ICP-MS was employed in the measurement of silver leaching from a silver nano-particle impregnated polymer material that could be used in the production of catheters. Silver leaching from a catheter is potentially desirable due to its anti-microbial properties. The study of this leaching revealed that significant quantities of silver were being transferred from the polymer into surrounding human serum media over the period of seven days and beyond. For the most part this work was routine ICP-MS measurement, and did not involve research or development, so does not take part in the main body of this thesis. This work is discussed in Appendix 5

A Cooperative Federalism Approach to Shareholder Arbitration

Arbitration dominates private law across an ever-expanding range of fields. Its latest target, however, may not be a new field as much as a new form: mandatory arbitration provisions built into corporate charters and bylaws. Recent developments in corporate law coupled with signals from the Securities and Exchange Commission suggest that regulators may be newly receptive to shareholder arbitration. What they do next may have dramatic consequences for whether and how corporate and securities laws are enforced. The debate about the merits of arbitration is well worn, but its application to shareholder claims opens the door to a different set of responses. In particular, the overlapping authority of federal and state actors with respect to corporate law calls for approaches that sound in cooperative federalism. Yet cooperative-federalist approaches have been absent from recent debates about shareholder arbitration. This Essay explains why cooperative federalism is a natural fit for addressing these issues. Moreover, we marshal specific examples of cooperative solutions in this area that could help frame federal-state coordination going forward. Such a cooperative response would avoid unnecessary federal-state conflict and allow policymakers to approach shareholder arbitration with expertise, accountability, and mutual respect

Should the grading of colorectal adenocarcinoma include microsatellite instability status?

Adenocarcinomas of the colon and rectum are graded using a 2-tiered system into histologic low-grade and high-grade tumors based on the proportion of gland formation. The current grading system does not apply to subtypes of carcinomas associated with a high frequency of microsatellite instability (MSI), such as mucinous and medullary carcinomas. We investigated the combined effect of histologic grade and MSI status on survival for 738 patients with colorectal carcinoma (48% female; mean age at diagnosis 68.2 years). The proportion of high-grade adenocarcinoma was 18%. MSI was observed in 59 adenocarcinomas (9%), with higher frequency in high-grade tumors compared with low-grade tumors (20% versus 6%; P < .001). Using Cox regression models, adjusting for sex and age at diagnosis and stratifying by the American Joint Committee on Cancer stage, microsatellite stable (MSS) high-grade tumors were associated with increased hazard of all-cause and colorectal cancer specific mortality: hazard ratio 2.09 (95% confidence interval [CI], 1.58-2.77) and 2.54 (95% CI, 1.86-3.47), respectively, both P < .001. A new grading system separating adenocarcinoma into low grade (all histologic low grade and MSI high grade) and high grade (MSS histologic high grade) gave a lower Akaike information criterion value when compared with the current grading system and thus represented a better model fit to stratify patients according to survival. We found that patients with a high-grade adenocarcinoma had significantly shorter survival than patients with low-grade adenocarcinoma only if the tumor was MSS, suggesting that the grading of colorectal adenocarcinoma with high-grade histologic features should be made according to the MSI status of the tumor. (C) 2014 Elsevier Inc. All rights reserved

Colorectal cancer linkage on chromosomes 4q21, 8q13, 12q24, and 15q22

A substantial proportion of familial colorectal cancer (CRC) is not a consequence of known susceptibility loci, such as mismatch repair (MMR) genes, supporting the existence of additional loci. To identify novel CRC loci, we conducted a genome-wide linkage scan in 356 white families with no evidence of defective MMR (i.e., no loss of tumor expression of MMR proteins, no microsatellite instability (MSI)-high tumors, or no evidence of linkage to MMR genes). Families were ascertained via the Colon Cancer Family Registry multi-site NCI-supported consortium (Colon CFR), the City of Hope Comprehensive Cancer Center, and Memorial University of Newfoundland. A total of 1,612 individuals (average 5.0 per family including 2.2 affected) were genotyped using genome-wide single nucleotide polymorphism linkage arrays; parametric and non-parametric linkage analysis used MERLIN in a priori-defined family groups. Five lod scores greater than 3.0 were observed assuming heterogeneity. The greatest were among families with mean age of diagnosis less than 50 years at 4q21.1 (dominant HLOD = 4.51, α = 0.84, 145.40 cM, rs10518142) and among all families at 12q24.32 (dominant HLOD = 3.60, α = 0.48, 285.15 cM, rs952093). Among families with four or more affected individuals and among clinic-based families, a common peak was observed at 15q22.31 (101.40 cM, rs1477798; dominant HLOD = 3.07, α = 0.29; dominant HLOD = 3.03, α = 0.32, respectively). Analysis of families with only two affected individuals yielded a peak at 8q13.2 (recessive HLOD = 3.02, α = 0.51, 132.52 cM, rs1319036). These previously unreported linkage peaks demonstrate the continued utility of family-based data in complex traits and suggest that new CRC risk alleles remain to be elucidated. © 2012 Cicek et al

A Mechanism-Based Approach to the Identification of Age–Period–Cohort Models

This article offers a new approach to the identification of age-period-cohort (APC) models that builds on Pearl's work on nonparametric causal models, in particular his front-door criterion for the identification of causal effects. The goal is to specify the mechanisms through which the age, period, and cohort variables affect the outcome and in doing so identify the model. This approach allows for a broader set of identification strategies than has typically been considered in the literature and, in many circumstances, goodness of fit tests are possible. The authors illustrate the utility of the approach by developing an APC model for political alienation.Sociolog

Risk of colorectal cancer for carriers of mutations in MUTYH, with and without a family history of cancer

We studied 2332 individuals with monoallelic mutations in MUTYH among 9504 relatives of 264 colorectal cancer (CRC) cases with a MUTYH mutation. We estimated CRC risks through 70 years of age of 7.2% for male carriers of monoallelic mutations (95% confidence interval [CI], 4.6%-11.3%) and 5.6% for female carriers of monoallelic mutations (95% CI, 3.6%-8.8%), irrespective of family history. For monoallelic MUTYH mutation carriers with a first-degree relative with CRC diagnosed by 50 years of age who does not have the MUTYH mutation, risks of CRC were 12.5% for men (95% CI, 8.6%-17.7%) and 10% for women (95% CI, 6.7%-14.4%). Risks of CRC for carriers of monoallelic mutations in MUTYH with a first-degree relative with CRC are sufficiently high to warrant more intensive screening than for the general population

AD51B in Familial Breast Cancer

Common variation on 14q24.1, close to RAD51B, has been associated with breast cancer: rs999737 and rs2588809 with the risk of female breast cancer and rs1314913 with the risk of male breast cancer. The aim of this study was to investigate the role of RAD51B variants in breast cancer predisposition, particularly in the context of familial breast cancer in Finland. We sequenced the coding region of RAD51B in 168 Finnish breast cancer patients from the Helsinki region for identification of possible recurrent founder mutations. In addition, we studied the known rs999737, rs2588809, and rs1314913 SNPs and RAD51B haplotypes in 44,791 breast cancer cases and 43,583 controls from 40 studies participating in the Breast Cancer Association Consortium (BCAC) that were genotyped on a custom chip (iCOGS). We identified one putatively pathogenic missense mutation c.541C&gt;T among the Finnish cancer patients and subsequently genotyped the mutation in additional breast cancer cases (n = 5259) and population controls (n = 3586) from Finland and Belarus. No significant association with breast cancer risk was seen in the meta-analysis of the Finnish datasets or in the large BCAC dataset. The association with previously identified risk variants rs999737, rs2588809, and rs1314913 was replicated among all breast cancer cases and also among familial cases in the BCAC dataset. The most significant association was observed for the haplotype carrying the risk-alleles of all the three SNPs both among all cases (odds ratio (OR): 1.15, 95% confidence interval (CI): 1.11–1.19, P = 8.88 x 10−16) and among familial cases (OR: 1.24, 95% CI: 1.16–1.32, P = 6.19 x 10−11), compared to the haplotype with the respective protective alleles. Our results suggest that loss-of-function mutations in RAD51B are rare, but common variation at the RAD51B region is significantly associated with familial breast cancer risk

A simple measure with complex determinants: investigation of the correlates of self-rated health in older men and women from three continents

Self-rated health is commonly employed in research studies that seek to assess the health status of older individuals. Perceptions of health are, however, influenced by individual and societal level factors that may differ within and between countries. This study investigates levels of self-rated health (SRH) and correlates of SRH among older adults in Australia, United States of America (USA), Japan and South Korea. We conclude that when examining correlates of SRH, the similarities are greater than the differences between countries. There are however differences in levels of SRH which are not fully accounted for by the health correlates. Broad generalizations about styles of responding are not helpful for understanding these differences, which appear to be country- and possibly cohort-specific. When using SRH to characterize the health status of older people, it is important to consider earlier life experiences of cohorts as well as national and individual factors in later life. Further research is required to understand the complex societal influences on perceptions of health.The Australian data on which this research is based were drawn from several Australian longitudinal studies including: the Australian Longitudinal Study of Ageing (ALSA), the Australian Longitudinal Study of Women’s Health (ALSWH) and the Personality And Total Health Through Life Study (PATH). These studies were pooled and harmonized for the Dynamic Analyses to Optimize Ageing (DYNOPTA) project. DYNOPTA was funded by a National Health and Medical Research Council (NHMRC) grant (# 410215)

Restoring brain function after stroke - bridging the gap between animals and humans

Stroke is the leading cause of complex adult disability in the world. Recovery from stroke is often incomplete, which leaves many people dependent on others for their care. The improvement of long-term outcomes should, therefore, be a clinical and research priority. As a result of advances in our understanding of the biological mechanisms involved in recovery and repair after stroke, therapeutic opportunities to promote recovery through manipulation of poststroke plasticity have never been greater. This work has almost exclusively been carried out in preclinical animal models of stroke with little translation into human studies. The challenge ahead is to develop a mechanistic understanding of recovery from stroke in humans. Advances in neuroimaging techniques now enable us to reconcile behavioural accounts of recovery with molecular and cellular changes. Consequently, clinical trials can be designed in a stratified manner that takes into account when an intervention should be delivered and who is most likely to benefit. This approach is expected to lead to a substantial change in how restorative therapeutic strategies are delivered in patients after stroke