A Modest Addendum to the English Sediment Core Meta-Database

Compilations of previous studies provide researchers with a source of valuable secondary data for re-analysis, an access route to identify relevant literature and an opportunity to systematically evaluate the research which is conducted and published. Recently Suggitt et al. (2015 Veg Hist Archbot 24, 743–747) presented a valuable compilation of core records for England. Here we present an extended version of this English Sediment Core Meta-database which includes data for 100 additional cores and improves the consistency of presentation. Despite these additions there are clearly large gaps remaining. Maximising the value of such meta-databases requires a community effort and we hope that this contribution will be a first step towards achieving this

Randomized phase II study of stereotactic body radiotherapy and interleukin-2 versus interleukin-2 in patients with metastatic melanoma.

BACKGROUND: A pilot study of stereotactic body radiation therapy (SBRT) followed by high-dose interleukin-2 (IL-2) showed a higher than anticipated objective response rate (ORR) among patients with metastatic melanoma (MM). We performed a prospective randomized study to determine if the ORR of SBRT + IL-2 was greater than IL-2 monotherapy in patients with advanced melanoma. METHODS: Patients with MM who had adequate physiological reserve for IL-2 and at least one site suitable for SBRT were eligible. There was a 1:1 randomization to SBRT + IL-2 or IL-2 monotherapy. Patients received one or two doses of SBRT (20 Gy per fraction) with the last dose administered 3 days before starting the first cycle of IL-2. IL-2 (600,000 IU per kg via intravenous bolus infusion) was given every 8 hours for a maximum of 14 doses with a second cycle after a 2-week rest. Responding patients received up to six IL-2 cycles. Patients assigned to IL-2 monotherapy who exhibited progression of melanoma after cycle 2 were allowed to crossover and receive SBRT and additional IL-2. Response Evaluation Criteria in Solid Tumors 1.1 criteria were applied to non-irradiated lesions for response assessment. RESULTS: 44 patients were included in the analysis. The ORR in the SBRT + IL-2 group was 54%: 21% complete response (CR), 33% partial response (PR), 21% stable disease (SD) and 25% progressive disease (PD). The ORR in patients receiving IL-2 monotherapy was 35%: 15% CR, 20% PR, 25% SD and 40% PD. Seven patients assigned to IL-2 subsequently received SBRT + IL-2. One CR and two PRs were observed in the crossover group. There was no difference in progression-free or overall survival (OS). At 5 years the OS was 26% in the SBRT + IL-2 group and 25% in the IL-2 monotherapy group. The disease control rate (DCR) was higher in the SBRT + IL-2 group (75% vs 60%, p=0.34). CONCLUSIONS: SBRT + IL-2 induced more objective responses with a higher DCR compared to IL-2 monotherapy in MM. IL-2 monotherapy resulted in a significantly higher ORR than anticipated. Some patients in the crossover group also achieved objective responses. TRIAL REGISTRATION NUMBER: NCT01416831

Improving Medicines use in People with Polypharmacy in Primary Care (IMPPP): Protocol for a multicentre cluster randomised trial comparing a complex intervention for medication optimization against usual care.

IntroductionPolypharmacy is increasingly common, and associated with undesirable consequences. Polypharmacy management necessitates balancing therapeutic benefits and risks, and varying clinical and patient priorities. Current guidance for managing polypharmacy is not supported by high quality evidence. The aim of the Improving Medicines use in People with Polypharmacy in Primary Care (IMPPP) trial is to evaluate the effectiveness of an intervention to optimise medication use for patients with polypharmacy in a general practice setting.MethodsThis trial will use a multicentre, open-label, cluster-randomised controlled approach, with two parallel groups. Practices will be randomised to a complex intervention comprising structured medication review (including interprofessional GP/pharmacist treatment planning and patient-facing review) supported by performance feedback, financial incentivisation, clinician training and clinical informatics (intervention), or usual care (control). Patients with polypharmacy and triggering potentially inappropriate prescribing (PIP) indicators will be recruited in each practice using a computerised search of health records. 37 practices will recruit 50 patients, and review them over a 26-week intervention delivery period. The primary outcome is the mean number of PIP indicators triggered per patient at 26 weeks follow-up, determined objectively from coded GP electronic health records. Secondary outcomes will include patient reported outcome measures, and health and care service use. The main intention-to-treat analysis will use linear mixed effects regression to compare number of PIP indicators triggered at 26 weeks post-review between groups, adjusted for baseline (pre-randomisation) values. A nested process evaluation will explore implementation of the intervention in primary care.Ethics and disseminationThe protocol and associated study materials have been approved by the Wales REC 6, NHS Research Ethics Committee (REC reference 19/WA/0090), host institution and Health Research Authority. Research outputs will be published in peer-reviewed journals and relevant conferences, and additionally disseminated to patients and the public, clinicians, commissioners and policy makers.Isrctn registration90146150 (28/03/2019)

Breast Cancer Screening Recommendations: A Review for Primary Care Nurse Practitioners

The incidence of breast cancer has declined in recent years, however, it remains a significant health problem in the United States. The reduction in incidence may be attributed to both a decrease in combination hormone therapy due to increased breast cancer risk and an increase in the use of screening mammography. Controversy in the guidelines continues regarding the frequency of screening mammography, the use of clinical breast examination and the value of breast self examination. This paper provides nurse practitioners with information to assist them in making recommendations for breast cancer screening to patients

Surface Enhanced Raman Spectroscopy Detection of Neurotransmitters

Current in vivo methods for analyzing neurochemicals include invasive procedures, such as drilling a hole through the skull. Common in vitro methods of neurotransmitter detection through analysis of biofluids require considerable time to gather and process data. Therefore, there is a need for the development of a detection method that is non-invasive, selective, rapid, and label free. Surface enhanced Raman spectroscopy (SERS) would be advantageous for the detection of local concentrations of neurotransmitters in non-invasively collected biofluids. This method of Raman spectroscopy provides enhanced signals through the adsorption of low concentration analytes to gold nanoparticles, which creates an oscillating electric field called the localized surface plasmon resonance (LSPR). In the Sharma lab, we focus on the development of biosensors for early disease detection through the use of gold nanoparticles to achieve SERS detection of five major neurochemicals. In order to optimize enhancement, we vary the acidity of the nanoparticle solution. SERS allows for a highly selective detection method that provides rapid sample analysis. We present the development of our detection method along with results on the SERS detection of five major neurotransmitters in the micromolar to nanomolar range

Testing the effectiveness of interactive training on sexual harassment and assault in field science [Registered Report Stage 1 protocol]

Abstract:   Fieldwork is a critical tool for scientific research, particularly in applied disciplines. Yet fieldwork is often unsafe, particularly for members of historically marginalized groups and those whose presence in scientific spaces threatens traditional hierarchies of power, authority, and legitimacy. Research is needed to identify interventions that prevent sexual harassment and assault from occurring in the first place. We will conduct a quasi-experiment assessing the impacts of a 90-minute interactive training on field-based staff in a United States state government agency. We hypothesize that the knowledge-based interventions, social modeling, and mastery experiences included in the training will increase participants’ sexual harassment and assault prevention knowledge, self-efficacy, behavioral intention, and behavior after the training compared to a control group of their peers. Results will confirm or refute the utility of a peer-led interactive intervention for improving workplace culture and safety in scientific settings. </p

Improving Medicines use in People with Polypharmacy in Primary Care (IMPPP)

Polypharmacy is increasingly common, and is associated with undesirable consequences. Polypharmacy management necessitates balancing therapeutic benefits and risks, and varying clinical and patient priorities. Current guidance for managing polypharmacy is not supported by high quality evidence. The aim of the Improving Medicines use in People with Polypharmacy in Primary Care (IMPPP) trial is to evaluate the effectiveness of an intervention to optimise medication use for patients with polypharmacy in a general practice setting

Neoantigen T-Cell Receptor Gene Therapy in Pancreatic Cancer.

A patient with progressive metastatic pancreatic cancer was treated with a single infusion of 16.2×109 autologous T cells that had been genetically engineered to clonally express two allogeneic HLA-C*08:02-restricted T-cell receptors (TCRs) targeting mutant KRAS G12D expressed by the tumors. The patient had regression of visceral metastases (overall partial response of 72% according to the Response Evaluation Criteria in Solid Tumors, version 1.1); the response was ongoing at 6 months. The engineered T cells constituted more than 2% of all the circulating peripheral-blood T cells 6 months after the cell transfer. In this patient, TCR gene therapy targeting the KRAS G12D driver mutation mediated the objective regression of metastatic pancreatic cancer. (Funded by the Providence Portland Medical Foundation.)