The Exemption Status of the Bona Fide Pledgee of Unregistered Securities Under the Securities Act of 1933

The number of connections of photovoltaic (PV) to distribution network is increasing. Very few PV connection guidelines that distribution system operators (DSOs) can refer to have been found. This paper deals with network planning guidelines for distribution networks with PV. The paper aims to identify planning rules that are relatively easy to implement.QC 20140625</p

Sentinel lymph node biopsies in early stage oral and oropharyngeal carcinoma : a retrospective single-centre experience

The aim of this retrospective study was to analyse a consecutive series of patients with oral and oropharyngeal carcinoma who had had sentinel lymph node biopsy (SLNB) at our hospital during 2008-2017. A total of 70 patients with clinically and radiologically confirmed primary oral (n = 67) or oropharyngeal (n = 3) carcinoma, with no signs of metastatic lymph nodes preoperatively (clinically N0) were included. Patients' clinical and personal data, characteristics of the tumours, sentinel lymph node (SLN) status and outcomes were recorded. Eight patients had invaded SLN. Two patients with clear sentinel lymph node biopsies had recurrences in the cervical lymph nodes with no new primary tumour as origin. The negative predictive value (NPV) and sensitivity for SLNB were 97% and 80%, respectively. The depth of invasion was an individual predictor for cervical lymph node metastasis (p = 0.043). Single photo emission computed tomography (SPECT) detected fewer SLN in patients with invaded lymph nodes than in patients with clear lymph nodes (p = 0.018). Our data support the use of SLNB as a minimally invasive method for staging the cervical lymph nodes among patients with cN0 oral and oropharyngeal carcinoma. Our results further confirm that greater depth of invasion is associated with cervical lymph node metastases. (c) 2020 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.Peer reviewe

Adolescents' and young adults' experiences of childhood cancer: descriptions of daily life 5 years after diagnosis

Background: Survivors of childhood cancer are a growing population in society. These young people have a high risk of developing chronic health problems with a potential strong impact on their lives. How a childhood cancer experience affects survivors in adolescence has only been studied to a limited extent, and an increased understanding of this young group is needed to improve follow-up care. Objective: The aim was to gain a deeper understanding of how childhood cancer affects the lives of survivors by exploring adolescents' and young adults' views of what it is like living with this experience. Methods: Fifty-nine people 11-22 years old were interviewed a median of five years after diagnosis (response rate 66%). Data was collected through telephone interviews and analysed with qualitative content analysis. Results: Three groups of informants were identified according to their descriptions of influence on daily life: ‘Feeling like anyone else’ (the informants who described that the cancer experience had almost no influence on current life) (49%), ‘Feeling almost like others’(those who described some influence) (44%) and ‘Feeling different’ (those describing a great influence on current life) (7%). Conclusions: Most of the adolescents and young adults appear to get along well, although many informants described that life was affected to some extent by having had cancer. Implications for Practice: Necessary follow-up care that can identify those young survivors of childhood cancer having trouble with daily life and offer them support to strengthen their resources in managing difficulties in relation to having had cancer

Heterogeneity in Blood Pressure Response to 4 Antihypertensive Drugs: A Randomized Clinical Trial

Importance: Hypertension is the leading risk factor for premature death worldwide. Multiple blood pressure-lowering therapies are available but the potential for maximizing benefit by personalized targeting of drug classes is unknown. Objective: To investigate and quantify the potential for targeting specific drugs to specific individuals to maximize blood pressure effects. Design, Setting, and Participants: A randomized, double-blind, repeated crossover trial in men and women with grade 1 hypertension at low risk for cardiovascular events at an outpatient research clinic in Sweden. Mixed-effects models were used to assess the extent to which individuals responded better to one treatment than another and to estimate the additional blood pressure lowering achievable by personalized treatment. Interventions: Each participant was scheduled for treatment in random order with 4 different classes of blood pressure-lowering drugs (lisinopril [angiotensin-converting enzyme inhibitor], candesartan [angiotensin-receptor blocker], hydrochlorothiazide [thiazide], and amlodipine [calcium channel blocker]), with repeated treatments for 2 classes. Main Outcomes and Measures: Ambulatory daytime systolic blood pressure, measured at the end of each treatment period. Results: There were 1468 completed treatment periods (median length, 56 days) recorded in 270 of the 280 randomized participants (54% men; mean age, 64 years). The blood pressure response to different treatments varied considerably between individuals (P <.001), specifically for the choices of lisinopril vs hydrochlorothiazide, lisinopril vs amlodipine, candesartan vs hydrochlorothiazide, and candesartan vs amlodipine. Large differences were excluded for the choices of lisinopril vs candesartan and hydrochlorothiazide vs amlodipine. On average, personalized treatment had the potential to provide an additional 4.4 mm Hg-lower systolic blood pressure. Conclusions and Relevance: These data reveal substantial heterogeneity in blood pressure response to drug therapy for hypertension, findings that may have implications for personalized therapy. Trial Registration: ClinicalTrials.gov Identifier: NCT02774460

Toll-like receptor 2 and Toll-like receptor 4 predict favorable prognosis in local pancreatic cancer

Toll-like receptors play an essential role in our innate immune system and are a focus of interest in contemporary cancer research. Thus far, Toll-like receptors have shown promising prognostic value in carcinomas of the oral cavity, colon, and ovaries, but the prognostic role of Toll-like receptors in pancreatic ductal adenocarcinoma has not been established. We set out to investigate whether Toll-like receptor expression could serve in prognostic evaluation in pancreatic ductal adenocarcinoma, as well. Our study comprised 154 consecutive stage I?III pancreatic ductal adenocarcinoma patients surgically treated at Helsinki University Hospital between 2002 and 2011. Patients who received neoadjuvant therapy were excluded. Tissue microarrays and immunohistochemistry allowed assessment of the expression of Toll-like receptor 2 and Toll-like receptor 4 in pancreatic ductal adenocarcinoma tissue, and we matched staining results against clinicopathological parameters using Fisher?s test. For survival analysis, we used the Kaplan?Meier method and the log-rank test, and the Cox regression proportional hazard model for univariate and multivariate analyses. The hazard ratios were calculated for disease-specific overall survival. Strong Toll-like receptor 2 expression was observable in 51 (34%) patients and strong Toll-like receptor 4 in 50 (33%) patients. Overall, neither marker showed any direct coeffect on survival. However, strong Toll-like receptor 2 expression predicted better survival when tumor size was less than 30?mm (hazard ratio?=?0.30; 95% confidence interval?=?0.13?0.69; p?=?0.005), and strong Toll-like receptor 4 expression predicted better survival in patients with lymph-node-negative disease (hazard ratio?=?0.21; 95% confidence interval?=?0.07?0.65; p?=?0.006). In conclusion, we found strong Toll-like receptor 2 and Toll-like receptor 4 expressions to be independent factors of better prognosis in pancreatic ductal adenocarcinoma patients with stage I?II disease.Peer reviewe

Growth Differentiation Factor 15 at 1 Month After an Acute Coronary Syndrome Is Associated With Increased Risk of Major Bleeding.

BACKGROUND: Growth differentiation factor-15 (GDF-15) is related to major bleeding when measured at initial presentation in patients with acute coronary syndromes (ACSs) treated with dual antiplatelet therapy. It is unknown whether follow-up measurements provide additional information. The objective of this study was to investigate whether GDF-15 measured 1 month after an ACS provides additional information beyond the baseline levels with regard to the risk of major bleeding. METHODS AND RESULTS: GDF-15 was measured at baseline and at 1 month after an ACS in 4049 patients included in the PLATelet inhibition and patient Outcomes (PLATO) trial. The association between 1-month GDF-15 level and non-coronary artery bypass grafting surgery-related major bleeding was assessed by a multivariable Cox model, adjusting for baseline GDF-15, age, anemia, impaired renal function, history of gastrointestinal bleeding, and sex. Elevated GDF-15 (>1800 ng/L) at 1 month was associated with an increased risk of non-coronary artery bypass grafting-related major bleeding (3.9% versus 1.2%; hazard ratio, 3.38; 95% CI, 1.89-6.06), independent of baseline GDF-15. Patients who had elevated GDF-15 levels at baseline and subsequent nonelevated GDF-15 at 1 month had a similar risk as patients who had nonelevated levels at both measurements. CONCLUSIONS: GDF-15 at 1 month after an ACS is related to the risk of bleeding during DAPT and provides additional information on the bleeding risk beyond baseline GDF-15 levels. GDF-15 levels may therefore be useful as part of decision support concerning long-term antithrombotic treatment in patients post-ACS. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00391872