Postoperative radiotherapy in women with early operable breast cancer (Scottish Breast Conservation Trial): 30-year update of a randomised, controlled, phase 3 trial.

Background: Breast-conserving surgery, adjuvant systemic therapy, and radiotherapy are the standard of care for most women with early breast cancer. There are few reports of clinical outcomes beyond the first decade of follow-up of randomised trials comparing breast-conserving surgery with or without radiotherapy. We present a 30-year update of the Scottish Breast Conservation Trial.

Evaluation of Decentralized Verifiable Credentials to Authenticate Authorized Trading Partners and Verify Drug Provenance.

Summary: In 2013, the Drug Supply Chain Security Act (DSCSA) was signed into law to address the growing threat of counterfeit drugs and to ensure prescription drugs remain safe and effective for patients. As part of this law, US pharmaceutical supply chain stakeholders are required to confirm the authorized status of trading partners for transactions and information disclosures, even when there is no prior business relationship. While larger Authorized Trading Partners (ATPs) have connectivity solutions in place, newer and smaller ATPs have not traditionally participated, including tens of thousands of dispensers.

Diagnostic accuracy of core biopsy in patients presenting with axillary lymphadenopathy and suspected non-breast malignancy.

Introduction: Excision biopsy has been the investigation of choice for patients presenting with pathological axillary lymphadenopathy without a breast abnormality. Core biopsy of nodes can provide sufficient tissue for diagnosis and has advantages in terms of morbidity and speed of diagnosis. This study evaluates the diagnostic accuracy of core biopsy in patients presenting with axillary lymphadenopathy.

Ready-to-use nanopore platform for the detection of any DNA/RNA oligo at attomole range using an Osmium tagged complementary probe.

Nanopores can serve as single molecule sensors. We exploited the MinION, a portable nanopore device from Oxford Nanopore Technologies, and repurposed it to detect any DNA/RNA oligo (target) in a complex mixture by conducting voltage-driven ion-channel measurements. The detection and quantitation of the target is enabled by the use of a unique complementary probe.

A catalogue of biochemically diverse CRISPR-Cas9 orthologs.

Bacterial Cas9 nucleases from type II CRISPR-Cas antiviral defence systems have been repurposed as genome editing tools. Although these proteins are found in many microbes, only a handful of variants are used for these applications. Here, we use bioinformatic and biochemical analyses to explore this largely uncharacterized diversity.

Therminator DNA Polymerase: Modified Nucleotides and Unnatural Substrates.

A variant of 9°N DNA polymerase [Genbank ID (AAA88769.1)] with three mutations (D141A, E143A, A485L) and commercialized under the name "Therminator DNA polymerase" has the ability to incorporate a variety of modified nucleotide classes. This Review focuses on how Therminator DNA Polymerase has enabled new technologies in synthetic biology and DNA sequencing.

Cash on delivery: Results of a randomized experiment to promote maternal health care in Kenya.

We conducted a randomized controlled experiment to test whether vouchers, cash transfers, and SMS messages were effective in boosting facility delivery rates among poor, pregnant women in rural Kenya. We find a strong effect of the full vouchers and the conditional cash transfers: 48% of women with access to both interventions delivered in a health facility, while only 36% of those with neither did. Amongst women who did not receive a cash transfer, we find that a small copayment dramatically reduced voucher effectiveness, suggesting a discontinuous impact of cost-sharing on the demand for health services.

The Stressed Executive: Sources and Predictors of Stress Among Participants in an Executive Health Program.

Background: Stress is highly prevalent in the U.S. society, especially in executives, and is a well-documented risk factor for a wide range of medical disorders.

Effect of community health clubs on child diarrhoea in western Rwanda: cluster-randomised controlled trial.

Background: Community health clubs are multi-session village-level gatherings led by trained facilitators and designed to promote healthy behaviours mainly related to water, sanitation, and hygiene. They have been implemented in several African and Asian countries but have never been evaluated rigorously. We aimed to evaluate the effect of two versions of the community health club model on child health and nutrition outcomes.

The long-run poverty and gender impacts of mobile money.

Mobile money, a service that allows monetary value to be stored on a mobile phone and sent to other users via text messages, has been adopted by the vast majority of Kenyan households. We estimate that access to the Kenyan mobile money system M-PESA increased per capita consumption levels and lifted 194,000 households, or 2% of Kenyan households, out of poverty. The impacts, which are more pronounced for female-headed households, appear to be driven by changes in financial behavior-in particular, increased financial resilience and saving-and labor market outcomes, such as occupational choice, especially for women, who moved out of agriculture and into business.

Nottingham Prognostic Index Plus: Validation of a clinical decision making tool in breast cancer in an independent series.

The Nottingham Prognostic Index Plus (NPI+) is a clinical decision making tool in breast cancer (BC) that aims to provide improved patient outcome stratification superior to the traditional NPI. This study aimed to validate the NPI+ in an independent series of BC. Eight hundred and eighty five primary early stage BC cases from Edinburgh were semi-quantitatively assessed for 10 biomarkers [Estrogen Receptor (ER), Progesterone Receptor (PgR), cytokeratin (CK) 5/6, CK7/8, epidermal growth factor receptor (EGFR), HER2, HER3, HER4, p53, and Mucin 1] using immunohistochemistry and classified into biological classes by fuzzy logic-derived algorithms previously developed in the Nottingham series.

Child diarrhoea and nutritional status in rural Rwanda: a cross-sectional study to explore contributing environmental and demographic factors.

Objective: To explore associations of environmental and demographic factors with diarrhoea and nutritional status among children in Rusizi district, Rwanda.

Methods: We obtained cross-sectional data from 8847 households in May-August 2013 from a baseline survey conducted for an evaluation of an integrated health intervention. We collected data on diarrhoea, water quality, and environmental and demographic factors from households with children <5, and anthropometry from children <2.

Pooled long-term outcomes from two randomized trials of axillary node sampling with axillary radiotherapy versus axillary node clearance in patients with operable node-positive breast cancer.

Background: The aim was to determine long-term overall, breast cancer-specific and metastasis-free survival as well as axillary relapse rate from a pooled analysis of two randomized trials in women with operable breast cancer. These trials compared axillary node sampling (ANS), combined with axillary radiotherapy (AXRT) if the sampled nodes were involved, with axillary node clearance (ANC).

Methods: Data from two clinical trials at the Edinburgh Breast Unit that randomized patients between 1980 and 1995 were pooled.

Results of a large-scale randomized behavior change intervention on road safety in Kenya.

Road accidents kill 1.3 million people each year, most in the developing world. We test the efficacy of evocative messages, delivered on stickers placed inside Kenyan matatus, or minibuses, in reducing road accidents.

FKBPL: a marker of good prognosis in breast cancer.

FK506-binding protein-like (FKBPL) has established roles as an anti-tumor protein, with a therapeutic peptide based on this protein, ALM201, shortly entering phase I/II clinical trials. Here, we evaluated FKBPL's prognostic ability in primary breast cancer tissue, represented on tissue microarrays (TMA) from 3277 women recruited into five independent retrospective studies, using immunohistochemistry (IHC). In a meta-analysis, FKBPL levels were a significant predictor of BCSS; low FKBPL levels indicated poorer breast cancer specific survival (BCSS) (hazard ratio (HR) = 1.

Impact of intermittent preventive treatment in pregnancy with azithromycin-containing regimens on maternal nasopharyngeal carriage and antibiotic sensitivity of Streptococcus pneumoniae, Haemophilus influenzae, and Staphylococcus aureus: a cross-sectional survey at delivery.

Sulfadoxine-pyrimethamine (SP) plus azithromycin (AZ) (SPAZ) has the potential for intermittent preventive treatment of malaria in pregnancy (IPTp), but its use could increase circulation of antibiotic-resistant bacteria associated with severe pediatric infections. We evaluated the effect of monthly SPAZ-IPTp compared to a single course of SP plus chloroquine (SPCQ) on maternal nasopharyngeal carriage and antibiotic susceptibility of Streptococcus pneumoniae, Haemophilus influenzae, and Staphylococcus aureus at delivery among 854 women participating in a randomized controlled trial in Papua New Guinea. Serotyping was performed, and antibiotic susceptibility was evaluated by disk diffusion and Etest.

Breast-conserving surgery with or without irradiation in women aged 65 years or older with early breast cancer (PRIME II): a randomised controlled trial.

Background: For most older women with early breast cancer, standard treatment after breast-conserving surgery is adjuvant whole-breast radiotherapy and adjuvant endocrine treatment. We aimed to assess the effect omission of whole-breast radiotherapy would have on local control in older women at low risk of local recurrence at 5 years.

Methods: Between April 16, 2003, and Dec 22, 2009, 1326 women aged 65 years or older with early breast cancer judged low-risk (ie, hormone receptor-positive, axillary node-negative, T1-T2 up to 3 cm at the longest dimension, and clear margins; grade 3 tumour histology or lymphovascular invasion, but not both, were permitted), who had had breast-conserving surgery and were receiving adjuvant endocrine treatment, were recruited into a phase 3 randomised controlled trial at 76 centres in four countries.

Time dependence of biomarkers: non-proportional effects of immunohistochemical panels predicting relapse risk in early breast cancer.

Background: We investigated the impact of follow-up duration to determine whether two immunohistochemical prognostic panels, IHC4 and Mammostrat, provide information on the risk of early or late distant recurrence using the Edinburgh Breast Conservation Series and the Tamoxifen vs Exemestane Adjuvant Multinational (TEAM) trial.

Methods: The multivariable fractional polynomial time (MFPT) algorithm was used to determine which variables had possible non-proportional effects. The performance of the scores was assessed at various lengths of follow-up and Cox regression modelling was performed over the intervals of 0-5 years and >5 years.

A Morbidity Screening Tool for identifying fatigue, pain, upper limb dysfunction and lymphedema after breast cancer treatment: a validity study.

Purpose: This study aimed to investigate validity of a newly developed Morbidity Screening Tool (MST) to screen for fatigue, pain, swelling (lymphedema) and arm function after breast cancer treatment.

Methods: A cross-sectional study included women attending reviews after completing treatment (surgery, chemotherapy and radiotherapy), without recurrence, who could read English. They completed the MST and comparator questionnaires: Disability of the Arm, Shoulder and Hand questionnaire (DASH), Chronic Pain Grade Questionnaire (CPGQ), Lymphedema and Breast Cancer Questionnaire (LBCQ) and Functional Assessment of Cancer Therapy questionnaire with subscales for fatigue (FACT F) and breast cancer (FACT B + 4).

Comparison of breast cancer-related lymphedema (upper limb swelling) prevalence estimated using objective and subjective criteria and relationship with quality of life.

This study aimed to investigate lymphedema prevalence using three different measurement/diagnostic criterion combinations and explore the relationship between lymphedema and quality of life for each, to provide evaluation of rehabilitation. Cross-sectional data from 617 women attending review appointments after completing surgery, chemotherapy, and radiotherapy included the Morbidity Screening Tool (MST; criterion: yes to lymphedema); Lymphedema and Breast Cancer Questionnaire (LBCQ; criterion: yes to heaviness and/or swelling); percentage limb volume difference (perometer: %LVD; criterion: 10%+ difference); and the Functional Assessment of Cancer Therapy breast cancer-specific quality of life tool (FACT B+4). Perometry measurements were conducted in a clinic room.

GSK3β and cyclin D1 expression predicts outcome in early breast cancer patients.

Glycogen synthase kinase 3β (GSK3β) is phosphorylated and inactivated by the phosphoinositide 3 kinase PI3K/Akt pathway. Activation of Akt phosphorylates GSK3β preventing phosphorylation of cyclin D1 which leads to accumulation and nuclear localisation of cyclin D1, activation of CDK4/6 and cell cycle progression. The CCND1 gene found at chromosome 11q13 has been shown to be amplified in approximately 15 % of breast cancers.