Sentinel node biopsy should be supplemented by axillary sampling in patients with small breast cancers

Axillary clearance provides important prognostic information but is associated with significant morbidity. Sentinel node biopsy can provide staging .141 patients with node negative early breast cancers-tumour size less than 1.5 cm measured clinically or by imaging had guided axillary sampling (sentinel lymph node biopsy in combination with axillary sampling). Four node axillary sampling improved the detection rate of axillary node metastases by 13.6% as compared to blue dye sentinel node biopsy alone. Positive sampled nodes strongly indicated the likelihood of further metastatic being revealed by axillary dissection (67%). Negative sampled nodes in combination with a positive sentinel node biopsy were associated with a much lower rate of further nodal involvement in the axillary clearance (8%).     

H2O2 is required for UVB-induced EGF receptor and downstream signaling pathway activation

Ultraviolet radiation (UVR)-induced receptor phosphorylation is increasingly recognized as a widely occurring phenomenon. However, the mechanisms, mediators, and sequence of events involved in this process remain ill-defined. We have recently shown that exposure of human keratinocytes to physiologic doses of ultraviolet B radiation (UVB) activates epidermal growth factor receptor (EGFR)/extracellular-regulated kinase 1 and 2 (ERK1/2), and p38 signaling pathways via reactive oxygen species. Here we demonstrate that UVB exposure increased intra- and extracellular H₂O₂ production rapidly in a time-dependent manner. An EGFR-specific monoclonal antibody abrogated EGFR autophosphorylation and markedly decreased the phosphorylation of ERK1/2 whereas p38 activation was unaffected. Overexpression of catalase strongly inhibited UVB-induced EGFR/ERK1/2 pathway activation. These findings establish the sequence of events after UVB irradiation: (i) H₂O₂ generation, (ii) EGFR phosphorylation, and (iii) ERK activation. Our results identify UVB-induced H₂O₂ as a second messenger that is required for EGFR and dependent downstream signaling pathways activation.     

Kathu Townlands: A High Density Earlier Stone Age Locality in the Interior of South Africa

Kathu Townlands is a high density Earlier Stone Age locality in the Northern Cape Province, South Africa. Here we present the first detailed information on this locality based on analysis of a sample of lithic material from excavations by P. Beaumont and field observations made in the course of fieldwork in 2013. The results confirm the remarkably high artefact density at Kathu Townlands and do not provide evidence consistent with high energy transport as a mechanism of site formation, suggesting that Kathu Townlands was the site of intensive exploitation of highly siliceous outcroppings of banded iron formation. The results presented here provide a first step towards understanding this complex locality and point to the need for further research and the importance of preserving this locality in the face of intensive and rapid development.     

Cytogenetic studies in Eigenmannia virescens (Sternopygidae, Gymnotiformes) and new inferences on the origin of sex chromosomes in the Eigenmannia genus

Background

Previous studies suggested that multiple domestication events in South and South-East Asia (Yunnan and surrounding areas) and India have led to the genesis of modern domestic chickens. Ha Giang province is a northern Vietnamese region, where local chickens, such as the H'mong breed, and wild junglefowl coexist. The assumption was made that hybridisation between wild junglefowl and Ha Giang chickens may have occurred and led to the high genetic diversity previously observed. The objectives of this study were i) to clarify the genetic structure of the chicken population within the Ha Giang province and ii) to give evidence of admixture with G. gallus. A large survey of the molecular polymorphism for 18 microsatellite markers was conducted on 1082 chickens from 30 communes of the Ha Giang province (HG chickens). This dataset was combined with a previous dataset of Asian breeds, commercial lines and samples of Red junglefowl from Thailand and Vietnam (Ha Noï). Measurements of genetic diversity were estimated both within-population and between populations, and a step-by-step Bayesian approach was performed on the global data set.

Results

The highest value for expected heterozygosity (> 0.60) was found in HG chickens and in the wild junglefowl populations from Thailand. HG chickens exhibited the highest allelic richness (mean A = 2.9). No significant genetic subdivisions of the chicken population within the Ha Giang province were found. As compared to other breeds, HG chickens clustered with wild populations. Furthermore, the neighbornet tree and the Bayesian clustering analysis showed that chickens from 4 communes were closely related to the wild ones and showed an admixture pattern.

Conclusion

In the absence of any population structuring within the province, the H'mong chicken, identified from its black phenotype, shared a common gene pool with other chickens from the Ha Giang population. The large number of alleles shared exclusively between Ha Giang chickens and junglefowl, as well as the results of a Bayesian clustering analysis, suggest that gene flow has been taking place from junglefowl to Ha Giang chickens.     

Association of practice size and pay-for-performance incentives with the quality of diabetes management in primary care

Background:

Not enough is known about the association between practice size and clinical outcomes in primary care. We examined this association between 1997 and 2005, in addition to the impact of the Quality and Outcomes Framework, a pay-for-performance incentive scheme introduced in the United Kingdom in 2004, on diabetes management.

Methods:

We conducted a retrospective open-cohort study using data from the General Practice Research Database. We enrolled 422 general practices providing care for 154 945 patients with diabetes. Our primary outcome measures were the achievement of national treatment targets for blood pressure, glycated hemoglobin (HbA_1c) levels and total cholesterol.

Results:

We saw improvements in the recording of process of care measures, prescribing and achieving intermediate outcomes in all practice sizes during the study period. We saw improvement in reaching national targets after the introduction of the Quality and Outcomes Framework. These improvements significantly exceeded the underlying trends in all practice sizes for achieving targets for cholesterol level and blood pressure, but not for HbA_1c level. In 1997 and 2005, there were no significant differences between the smallest and largest practices in achieving targets for blood pressure (1997 odds ratio [OR] 0.98, 95% confidence interval [CI] 0.82 to 1.16; 2005 OR 0.92, 95% CI 0.80 to 1.06 in 2005), cholesterol level (1997 OR 0.94, 95% CI 0.76 to 1.16; 2005 OR 1.1, 95% CI 0.97 to 1.40) and glycated hemoglobin level (1997 OR 0.79, 95% CI 0.55 to 1.14; 2005 OR 1.05, 95% CI 0.93 to 1.19).

Interpretation:

We found no evidence that size of practice is associated with the quality of diabetes management in primary care. Pay-for-performance programs appear to benefit both large and small practices to a similar extent.There is a well-established body of literature showing positive associations between volume of patients and clinical outcomes in health care, which has been documented by a systematic review.¹ However, this association has usually been examined in a limited number of discrete procedures, and most studies have involved hospital-based services rather than primary care settings.^2–5Improving our understanding of the association between volume of patients and outcomes in primary care is important for several reasons. First, most contacts with health systems occur in primary care settings, and optimizing the delivery of these services has the potential to improve the health of the population.⁶ Second, over the past decade, primary care has assumed greater responsibility for managing the growing burden of chronic disease.^7,8 Larger providers may be better resourced, through the employment of additional support staff and greater use of information technology, to deliver the systematic, structured care necessary for the effective management of chronic disease.^6,9 Third, larger providers may have been more responsive to nonfinancial and financial incentives, including pay for performance, implemented by payers aimed at improving the quality of care.^7,10 Fourth, in many countries, primary care is based around a predominance of small practices.^6,11,12 In 2006, 53% of practices in England and Wales had three or fewer family physicians.¹¹ In the same year in the United States, 30.3% of family physicians were in solo practice; 9.4% were in two-physician practices.¹²Despite the limited data available, concerns have been raised about the standards of care delivered by smaller family practices.¹³ In the United Kingdom and Canada, this has resulted in an explicit policy objective of encouraging smaller practices to amalgamate.^13,14Our study examines the associations between the size of practice and the quality of diabetes management in UK primary care settings between 1997 and 2005. We tested the hypotheses that patients attending larger family practices receive better care for diabetes and that the quality gap between larger and smaller practices has increased over the past decade. We also hypothesized that larger practices derived more benefit from the Quality and Outcomes Framework, a major pay-for-performance program in primary care introduced in 2004.