Lynch syndrome-associated breast cancers: clinicopathologic characteristics of a case series from the colon cancer family registry

Purpose: The recognition of breast cancer as a spectrum tumor in Lynch syndrome remains controversial. The aim of this study was to explore features of breast cancers arising in Lynch syndrome families. Experimental Design: This observational study involved 107 cases of breast cancer identified from the Colorectal Cancer Family Registry (Colon CFR) from 90 families in which (a) both breast and colon cancer co-occurred, (b) families met either modified Amsterdam criteria, or had at least one early-onset (<50 years) colorectal cancer, and (c) breast tissue was available within the biospecimen repository for mismatch repair (MMR) testing. Eligibility criteria for enrollment in the Colon CFR are available online. Breast cancers were reviewed by one pathologist. Tumor sections were stained for MLH1, PMS2, MSH2, and MSH6, and underwent microsatellite instability testing. Results: Breast cancer arose in 35 mutation carriers, and of these, 18 (51%) showed immunohistochemical absence of MMR protein corresponding to the MMR gene mutation segregating the family. MMR-deficient breast cancers were more likely to be poorly differentiated (P = 0.005) with a high mitotic index (P = 0.002), steroid hormone receptor–negative (estrogen receptor, P = 0.031; progesterone receptor, P = 0.022), and to have peritumoral lymphocytes (P = 0.015), confluent necrosis (P = 0.002), and growth in solid sheets (P < 0.001) similar to their colorectal counterparts. No difference in age of onset was noted between the MMR-deficient and MMR-intact groups. Conclusions: MMR deficiency was identified in 51% of breast cancers arising in known mutation carriers. Breast cancer therefore may represent a valid tissue option for the detection of MMR deficiency in which spectrum tumors are lacking

The effect of injury diagnosis on expected Postconcussion Syndrome (PCS) symptom reporting and illness perception

Objective: To determine if systematic variation of diagnostic terminology (i.e. concussion, minor head injury [MHI], mild traumatic brain injury [mTBI]) following a standardized injury description produced different expected symptoms and illness perceptions. We hypothesized that worse outcomes would be expected of mTBI, compared to other diagnoses, and that MHI would be perceived as worse than concussion. Method:108 volunteers were randomly allocated to conditions in which they read a vignette describing a motor vehicle accident-related mTBI followed by: a diagnosis of mTBI (n=27), MHI (n=24), concussion (n=31); or, no diagnosis (n=26). All groups rated: a) event ‘undesirability’; b) illness perception, and; c) expected Postconcussion Syndrome (PCS) and Posttraumatic Stress Disorder (PTSD) symptoms six months post injury. Results: On average, more PCS symptomatology was expected following mTBI compared to other diagnoses, but this difference was not statistically significant. There was a statistically significant group effect on undesirability (mTBI>concussion & MHI), PTSD symptomatology (mTBI & no diagnosis>concussion), and negative illness perception (mTBI & no diagnosis>concussion). Conclusion: In general, diagnostic terminology did not affect anticipated PCS symptoms six months post injury, but other outcomes were affected. Given that these diagnostic terms are used interchangeably, this study suggests that changing terminology can influence known contributors to poor mTBI outcome.

A comparison of new and existing mild traumatic brain injury vignettes : recommendations for research into post-concussion syndrome

OBJECTIVE: To review and compare the mild traumatic brain injury (mTBI) vignettes used in postconcussion syndrome (PCS) research, and to develop 3 new vignettes. METHOD: The new vignettes were devised using World Health Organization (WHO) mTBI diagnostic criteria [1]. Each vignette depicted a very mild (VM), mild (M), or severe (S) brain injury. Expert review (N = 27) and readability analysis was used to validate the new vignettes and compare them to 5 existing vignettes. RESULTS: The response rate was 44%. The M vignette and existing vignettes were rated as depicting a mTBI; however, the fit-to-criteria of these vignettes differed significantly. The fit-to-criteria of the M vignette was as good as that of 3 existing vignettes and significantly better than 2 other vignettes. As expected, the VM and S vignettes were a poor fit-to-criteria. CONCLUSIONS: These new vignettes will assist PCS researchers to test the limits of important etiology factors by varying the severity of depicted injuries.

Irritable bowel syndrome : the role of gut neuroendocrine peptides

Irritable bowel syndrome (IBS) is a common chronic disorder with a prevalence ranging from 5 to 10 % of the world's population. This condition is characterised by abdominal discomfort or pain, altered bowel habits, and often bloating and abdominal distension. IBS reduces quality of life in the same degree of impairment as major chronic diseases such as congestive heart failure and diabetes and the economic burden on the health care system and society is high. Abnormalities have been reported in the neuroendocrine peptides/amines of the stomach, small- and large intestine in patients with IBS. These abnormalities would cause disturbances in digestion, gastrointestinal motility and visceral hypersensitivity, which have been reported in patients with IBS. These abnormalities seem to contribute to the symptom development and appear to play a central role in the pathogenesis of IBS. Neuroendocrine peptides/amines are potential tools in the treatment and diagnosis of IBS. In particular, the cell density of duodenal chromogranin A expressing cells appears to be a good histopathological marker for the diagnosis of IBS with high sensitivity and specificity.

Quality of life in chronic fatigue syndrome

Whilst the debilitating fatigue experienced in patients suffering from Chronic Fatigue Syndrome (CFS) results in a subjective marked impairment in functioning, little research has investigated the impact of this disorder on quality of life. Forty-seven subjects with a confirmed diagnosis of CFS and 30 healthy controls were compared using the Sickness Impact Profile (SIP). A subgroup of subjects were interviewed regarding the impact CFS has had on their social and family relationships, work and recreational activities. Results from both the SIP and the interview revealed that CFS subjects had significantly impaired quality of life, especially in areas of social functioning. These findings highlight the importance of addressing the social isolation and loss of role functioning experienced by CFS sufferers.

The classic white formal shirt : a powerful emblem of social change

The classic white formal shirt is a widely and readily familiar object with considerable historical cultural significance to diverse social groups, and is therefore deserving of iconic status. For more than two hundred years, this singular item of apparel has been able to define and represent status, wealth, gender shifts and fashion norms. This garment, which has historically been relinquished to undergarment status, deserves an escalation of standing. The classic white formal shirt, for both men and women, can be used as a mirror to map considerable social change and the diversity of influence can be traced through many examples, including: Beau Brummell’s dandy status with his legendry white shirting; the Gibson Girl with her decorated white shirt style blouse defining ideals of female beauty; IBM business employees in the 1920s marketing trustworthiness through the uniformity of white shirts; the fictional advertising creation of the Arrow Collar Man, with his rigid white shirt, promoting American masculine ideals; and the iconic 1980s Hugo Boss style crisp white dress shirt symbolising power. The origins of the influence of the white shirt can be best traced in the Victorian era where it was an important symbol of wealth and class distinction and a powerful emblem of sobriety and uniformity for men. The pure white colour fulfilled masculine ideals of resolute austerity and the shirt, through its constancy, epitomised conformity and dependability. For women, the white cloth of the ‘shirt-waist’ from this period was also linked to ideals of cleanliness and purity and was seen as an iconic symbol of the new independent working class woman. This paper will propose that the classic white formal shirt, for both men and women, has been a powerful marker of social shifts in Western society and this underrated item of apparel, with limited scholarly writing, is worthy of iconic status. The discussion will trace the historical development of both the men’s and women’s white shirt, each with their own unique history, and in doing so highlight the considerable historical cultural significance associated with the white formal shirt. Discussed first will be the men’s white formal shirt.

Sunlight and other determinants of circulating 25-hydroxyvitamin D levels in black and white participants in a nationwide U.S. study

Circulating 25-hydroxyvitamin D (25(OH)D), a marker for vitamin D status, is associated with bone health and possibly cancers and other diseases; yet, the determinants of 25(OH)D status, particularly ultraviolet radiation (UVR) exposure, are poorly understood. Determinants of 25(OH)D were analyzed in a subcohort of 1,500 participants of the US Radiologic Technologists (USRT) Study that included whites (n 842), blacks (n 646), and people of other races/ethnicities (n 12). Participants were recruited monthly (20082009) across age, sex, race, and ambient UVR level groups. Questionnaires addressing UVR and other exposures were generally completed within 9 days of blood collection. The relation between potential determinants and 25(OH)D levels was examined through regression analysis in a random two-thirds sample and validated in the remaining one third. In the regression model for the full study population, age, race, body mass index, some seasons, hours outdoors being physically active, and vitamin D supplement use were associated with 25(OH)D levels. In whites, generally, the same factors were explanatory. In blacks, only age and vitamin D supplement use predicted 25(OH)D concentrations. In the full population, determinants accounted for 25 of circulating 25(OH)D variability, with similar correlations for subgroups. Despite detailed data on UVR and other factors near the time of blood collection, the ability to explain 25(OH)D was modest.

Benefiting white noise in developing feedforward active noise control systems

In many applications of active noise control (ANC), an online secondary path modelling method using a white noise as a training signal is required to ensure convergence of the system. The modelling accuracy and the convergence rate increase when a white noise with larger variance is used, however larger the variance increases the residual noise, which decreases performance of the system. The proposed algorithm uses the advantages of the white noise with larger variance to model the secondary path, but the injection is stopped at the optimum point to increase performance of the system. In this approach, instead of continuous injection of the white noise, a sudden change in secondary path during the operation makes the algorithm to reactivate injection of the white noise to adjust the secondary path estimation. Comparative simulation results shown in this paper indicate effectiveness of the proposed method.

Reining in equine metabolic syndrome : a gluttony of challenges

We humans are complicated creatures. Despite remarkable intellect, a fearsome ability to push boundaries and superior survival mechanisms, we are at times our own worst enemy. Metabolic syndrome continues to be a premier health problem in developed, and now increasingly in undeveloped, nations. It is spreading across the planet like an infectious disease and is costing us millions. Metabolic disease remains an important focus both for medical research and for governments desperate to ease the burden on already over-taxed health systems. Unlike some previous worldwide health epidemics, obesity-related diseases will require more than a single, silver bullet. A simple vaccine or treatment cannot overcome a lack of education, awareness and in some cases sheer determination; the human element of these diseases. Undeniably, these ‘human elements’ also complicate our ability, as veterinarians, to effectively manage the growing incidence of equine obesity and metabolic disease...

Changes in Knee Biomechanics After a Hip-Abductor Strengthening Protocol for Runners With Patellofemoral Pain Syndrome

Context: Very few authors have investigated the relationship between hip-abductor muscle strength and frontal-plane knee mechanics during running. Objective: To investigate this relationship using a 3-week hip-abductor muscle-strengthening program to identify changes in strength, pain, and biomechanics in runners with patellofemoral pain syndrome (PFPS). Design: Cohort study. Setting: University-based clinical research laboratory. Patients or Other Participants: Fifteen individuals (5 men, 10 women) with PFPS and 10 individuals without PFPS (4 men, 6 women) participated. Intervention(s): The patients with PFPS completed a 3-week hip-abductor strengthening protocol; control participants did not. Main Outcome Measure(s): The dependent variables of interest were maximal isometric hip-abductor muscle strength, 2-dimensional peak knee genu valgum angle, and stride-to-stride knee-joint variability. All measures were recorded at baseline and 3 weeks later. Between-groups differences were compared using repeated-measures analyses of variance. Results: At baseline, the PFPS group exhibited reduced strength, no difference in peak genu valgum angle, and increased stride-to-stride knee-joint variability compared with the control group. After the 3-week protocol, the PFPS group demonstrated increased strength, less pain, no change in peak genu valgum angle, and reduced stride-to-stride knee-joint variability compared with baseline. Conclusions: A 3-week hip-abductor muscle-strengthening protocol was effective in increasing muscle strength and decreasing pain and stride-to-stride knee-joint variability in individuals with PFPS. However, concomitant changes in peak knee genu valgum angle were not observed.

Stockholm Syndrome : architecture, politics and the human body

The exchange between the body and architecture walks a fine line between violence and pleasure. It is through the body that the subject engages with the architectural act, not via thought or reason, but through action. The materiality of architecture is the often the catalyst for some intense association; the wall that defines gender or class, the double bolted door that incarcerates, the enclosed privacy of the bedroom to the love affair. Architecture is the physical manifestation of Lefebvre’s inscribed space. It enacts the social and political systems through bodily occupation. Architecture, when tested by the occupation of bodies, anchors ideology in both space and time. The architect’s script can be powerful when rehearsed honestly to the building’s intentions and just as beautiful when rebuked by the act of protest or unfaithful occupation. This research examines this fine line of violence and pleasure in architecture through performance, in the work of Bryony Lavin’s play Stockholm and Revolving Door by Allora & Calzadilla as part of the recent Kaldor Public Art Projects exhibition 13 Rooms in Sydney. The research is underpinned by the work of Architect and theorist, Bernard Tschumi in his two essays, Violence of Architecture and The Pleasure of Architecture. Studying architecture through the lens of performance shifts the focus of examination from pure thought to the body; because architecture is occupied through the body and not the mind.

Book Review [White Bound: Nationalists, Antiracists, and the Shared Meanings of Race, by MW Hughey]

Dr Kathy A. Mills provides a critical synthesis and review of the new book by Matthew W. Hughey entitle: White Bound: Nationalists, Antiractists, and the Shared Meanings of Race, published by Standford University Press in 2012. A sample of Dr Mills' review reads: "The author positions race squarely at the center to challenge the shared assumptions of white supremacist logic on both sides of the debate. The clever thesis blurs the boundaries between “good whites” and “bad whites”, rendering the white reader intellectually stimulated, but existentially unchanged – White Bound – as the author ponders: “Perhaps we have met the enemy, and he [it] is us” (p.193)...The unanswered question that remains is: How do we resist the various “shades” of white supremacy to pursue counter-hegemonic practices?"

Prolegomenon to the study of the concepts of maturity and maturity model : from Black Horse to White Knight?

This paper takes its root in a trivial observation: management approaches are unable to provide relevant guidelines to cope with uncertainty, and trust of our modern worlds. Thus, managers are looking for reducing uncertainty through information’s supported decision-making, sustained by ex-ante rationalization. They strive to achieve best possible solution, stability, predictability, and control of “future”. Hence, they turn to a plethora of “prescriptive panaceas”, and “management fads” to bring simple solutions through best practices. However, these solutions are ineffective. They address only one part of a system (e.g. an organization) instead of the whole. They miss the interactions and interdependencies with other parts leading to “suboptimization”. Further classical cause-effects investigations and researches are not very helpful to this regard. Where do we go from there? In this conversation, we want to challenge the assumptions supporting the traditional management approaches and shed some lights on the problem of management discourse fad using the concept of maturity and maturity models in the context of temporary organizations as support for reflexion. Global economy is characterized by use and development of standards and compliance to standards as a practice is said to enable better decision-making by managers in uncertainty, control complexity, and higher performance. Amongst the plethora of standards, organizational maturity and maturity models hold a specific place due to general belief in organizational performance as dependent variable of (business) processes continuous improvement, grounded on a kind of evolutionary metaphor. Our intention is neither to offer a new “evidence based management fad” for practitioners, nor to suggest research gap to scholars. Rather, we want to open an assumption-challenging conversation with regards to main stream approaches (neo-classical economics and organization theory), turning “our eyes away from the blinding light of eternal certitude towards the refracted world of turbid finitude” (Long, 2002, p. 44) generating what Bernstein has named “Cartesian Anxiety” (Bernstein, 1983, p. 18), and revisit the conceptualization of maturity and maturity models. We rely on conventions theory and a systemic-discursive perspective. These two lenses have both information & communication and self-producing systems as common threads. Furthermore the narrative approach is well suited to explore complex way of thinking about organizational phenomena as complex systems. This approach is relevant with our object of curiosity, i.e. the concept of maturity and maturity models, as maturity models (as standards) are discourses and systems of regulations. The main contribution of this conversation is that we suggest moving from a neo-classical “theory of the game” aiming at making the complex world simpler in playing the game, to a “theory of the rules of the game”, aiming at influencing and challenging the rules of the game constitutive of maturity models – conventions, governing systems – making compatible individual calculation and social context, and possible the coordination of relationships and cooperation between agents with or potentially divergent interests and values. A second contribution is the reconceptualization of maturity as structural coupling between conventions, rather than as an independent variable leading to organizational performance.

SHOX gene is expressed in vertebral body growth plates in idiopathic and congenital scoliosis : implications for the etiology of scoliosis in Turner Syndrome

Reduced SHOX gene expression has been demonstrated to be associated with all skeletal abnormalities in Turner syndrome, other than scoliosis (and kyphosis). There is evidence to suggest that Turner syndrome scoliosis is clinically and radiologically similar to idiopathic scoliosis, although the phenotypes are dissimilar. This pilot gene expression study used relative quantitative real-time PCR (qRT-PCR) of the SHOX (short stature on X) gene to determine whether it is expressed in vertebral body growth plates in idiopathic and congenital scoliosis. After vertebral growth plate dissection, tissue was examined histologically and RNA was extracted and its integrity was assessed using a Bio-Spec Mini, NanoDrop ND-1000 spectrophotometer and standard denaturing gel electrophoresis. Following cDNA synthesis, gene-specific optimization in a Corbett RotorGene 6000 real-time cycler was followed by qRT-PCR of vertebral tissue. Histological examination of vertebral samples confirmed that only growth plate was analyzed for gene expression. Cycling and melt curves were resolved in triplicate for all samples. SHOX abundance was demonstrated in congenital and idiopathic scoliosis vertebral body growth plates. SHOX expression was 11-fold greater in idiopathic compared to congenital (n = 3) scoliosis (p = 0.027). This study confirmed that SHOX was expressed in vertebral body growth plates, which implies that its expression may also be associated with the scoliosis (and kyphosis) of Turner syndrome. SHOX expression is reduced in Turner syndrome (short stature). In this study, increased SHOX expression was demonstrated in idiopathic scoliosis (tall stature) and congenital scoliosis.

The null allele of GSTM1 does not affect susceptibility to solar keratoses in the Australian white population

Solar keratoses (SKs) are induced by exposure to UV radiation and are capable of undergoing transformation to squamous cell carcinoma (SCC).1 The two main factors influencing the occurrence of SK are the sensitivity of the skin to sunlight and the total duration of solar exposure. These factors are responsible for the high incidence of SK in Australia. Although the influence of genetic factors is not defined, there is evidence that the gene encoding the enzyme, glutathione S-transferase, may be implicated in cancer predisposition and therefore SK. Glutathione S-transferase Mu-1 (GSTM1) is an isoenzyme involved in the detoxification of carcinogens. The GSTM1 protein is completely absent in approximately 50% of white persons. This absence is caused by a homozygous gene deletion on chromosome 1p resulting in a null genotype.2 Katoh3 showed that the frequency of the GSTM1 null genotype was significantly higher in 85 patients with urothelial cancer (61.2%; p < 0.05), suggesting that the null genotype may increase cancer susceptibility. This finding was supported by Lafuente et al.4 who found evidence that persons who lack the GSTM1 gene have approximately twice the chance of experiencing malignant melanoma. Further research in the United Kingdom found that patients with two or more skin tumors of different types, basal cell carcinoma (BCC) and SCC, had a significantly higher frequency of GSTM1 null genotypes than controls (71%; p = 0.033). However the GSTM1 genotype in patients with only SCC was not excessive in this population.5 Persons residing in northern Australia have the highest incidence of nonmelanoma skin cancer (SCC and BCC) in the world6 and receive far greater solar exposure than persons residing in the United Kingdom. It is possible that the GSTM1 null genotype may affect susceptibility to SK, which may act as SCC precursors, in Australians exposed to these high levels of solar radiation.