Increasing integration of distributed energy resources (DER) in the electrical network has led distribution network operators to unprecedented challenges. This issue is compounded by the lack of monitoring infrastructure on the low voltage (LV) side of distribution networks at residential and utility sides. Non-intrusive load monitoring (NILM) methods provide an opportunity to add value to conventional electric measurements and to increase the observability of LV networks for the implementation of active management network techniques and intelligent control of DER. This work proposes a novel implementation of NILM methods for the identification of DER electrical signatures from aggregated measurements taken at the LV side of a distribution transformer. The implementation evaluates three machine learning algorithms such as k Nearest Neighbours (kNN), random forest and a multilayer perceptron under 100 scenarios of DER integration. A year of minutely reported values of electric current, voltage, active power, and reactive power are used to train and test the proposed model. The <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">$F_{1}$ </tex-math></inline-formula> scores achieved of 73% and 93% for Electrical Vehicles (EV) and rooftop photovoltaic (PV) respectively and processing times below <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">$314~\mu \text{s}$ </tex-math></inline-formula> on an Intel Core i7-8700 machine. These results confirm the relevance of the NILM method based on low frequency electric measurements from the real-time identification of DER.

BackgroundBevacizumab is an antiangiogenic recombinant humanized monoclonal antibody that inhibits tumor growth. FKB238, a bevacizumab biosimilar, has analytical pharmacokinetic and safety profiles similar to those of bevacizumab.ObjectiveThis phase III trial (NCT02810457) compared the efficacy and safety of FKB238 with that of bevacizumab in patients with advanced/recurrent non-squamous non-small-cell lung cancer (non-sq-NSCLC).MethodsThis global, multicenter, double-blind, parallel, randomized, comparative clinical trial enrolled and randomized patients with advanced/recurrent non-sq-NSCLC to receive intravenous infusions of either FKB238 15 mg/kg or bevacizumab 15 mg/kg. All patients received intravenous infusions of paclitaxel 200 mg/m2 and carboplatin (area under the curve 6.0) immediately prior to investigational products for 4–6 cycles. FKB238 and bevacizumab were administered on day 1 of each 21-day cycle until objective progressive disease by RECIST version 1.1 or other discontinuation criteria were met. The primary efficacy endpoint was overall response rate (ORR), including complete and partial response and based on blinded independent central review assessment. Other efficacy determinations included progression-free survival (PFS), overall survival (OS), and immunogenicity. Adverse events and severity were reported.ResultsThe ORR for the intent-to-treat (ITT) population (N = 731) was 51.6% in the FKB238 arm (N = 364) and 53.7% in the bevacizumab arm (N = 367). The FKB238:bevacizumab ORR ratio (ITT population) was 0.96 (90% confidence interval [CI] 0.86–1.08), and the difference in ORR (per-protocol set) between FKB238 and bevacizumab was − 0.02 (95% CI − 0.09 to 0.06). Both CIs fell within the prespecified equivalence margins. Estimated median PFS was 7.72 and 7.62 months in the FKB238 and bevacizumab arms, respectively (hazard ratio 0.97; 95% CI 0.82–1.16). Treatment-emergent adverse events (TEAEs) were reported for 94.2% and 95.1% of patients in the FKB238 and bevacizumab arms, respectively. Grade 3 or higher TEAEs were reported for 53.6% and 55.5% of patients in the FKB238 and bevacizumab arms, respectively. Serious TEAEs were reported for 25.1% and 26.0% of patients treated with FKB238 and bevacizumab, respectively.ConclusionsEfficacy equivalence was demonstrated between the two drugs, and safety profiles were similar. There were no meaningful differences in efficacy and safety between FKB238 or bevacizumab in patients with non-sq-NSCLC.Trial registration numberNCT02810457.

In recent years, payers, care purchasers and manufacturers have shown increasing interest in value-based arrangements (VBAs) for pharmaceutical products. However, critics claim VBAs do not meaningfully contribute to controlling cost or ensuring value of medicines. Through this research, we explored the impact of VBAs in the US, and whether broader implementation could bring additional economic benefit to the health system, patients, and caregivers beyond direct reductions in medicine cost.

e21728 Background: Bevacizumab (bev) is a recombinant humanized monoclonal antibody that binds selectively to VEGF-A and prevents it from interacting with its receptors, thereby inhibiting formation of new tumor vasculature to block tumor growth. FKB238, a bev biosimilar, has similar pharmacokinetic and safety profiles to originator bev (o-bev). This phase 3 trial (NCT02810457) compared the efficacy and safety of FKB238 with o-bev in patients with advanced/recurrent non-squamous non-small cell lung cancer (NS-NSCLC). Methods: This global, multicenter, double-blind, parallel, randomized, comparative clinical trial enrolled and randomized 731 patients with advanced/recurrent NS-NSCLC to receive 15 mg/kg intravenous (IV) infusion of either FKB238 (N = 364) or o-bev (N = 367). All patients received IV infusions of paclitaxel (200 mg/m2) and carboplatin (AUC 6.0) immediately prior to investigational drugs for 4-6 cycles. FKB238 and o-bev were administered on day 1 of each 21-day cycle until objective progressive disease or other discontinuation criteria were met. Results: The objective response rate (ORR) based on blinded independent central review assessment for the intent-to-treat population was 51.6% and 53.7% for patients in the FKB238 and o-bev arms, respectively. The FKB238/o-bev ORR ratio was 0.96 (90% CI: 0.86 to 1.08) and the 90% CI fell within the pre-specified equivalence margin. The estimated proportion of patients alive and progression free at 12 months was 25.0% in the FKB238 arm vs 25.3% in the o-bev arm (HR of 0.97, 95% CI 0.82-1.16). The estimated median progression-free survival was 7.72 months in the FKB238 arm and 7.62 months in the o-bev arm. TEAEs were reported for 94.2% (FKB238) and 95.1% (o-bev) of patients. TEAEs ≥ grade 3 were reported for 53.6% (FKB238) and 55.5% (o-bev) of patients. SAEs were reported for 25.1% and 26.0% of patients treated with FKB238 and o-bev, respectively. Conclusions: There were no meaningful differences in efficacy and safety between FKB238 or o-bev in patients with NS-NSCLC. ORR efficacy equivalence was demonstrated, and the safety profiles of both drugs were similar. Clinical trial information: NCT02810457.

This chapter describes a number of unique characteristics of working with families who own a business together using long term systemic family therapy approaches. I describe those families who are united by family and business links and the complexities and paradoxes that the dual attachment and relationships create for those families and the trusted advisors who work with them. The work involved with families in business requires the longer term view. The relationship between a trusted advisor and the family develops gradually over time in order to allow addressing the root of the problem rather than a “quick fix”. Addressing the longer term needs of a family business require a deep understanding of the profile of individual family members and their interrelationships; the specific needs of the business and its own developmental stage and an awareness of the financial strains of the business on the family and vice versa. In this chapter I describe some of the more salient characteristics and ways of working with families in business together; the complexities they face when they reflect on the dual aspect of their relationships; the misconceptions related to trust; the paradoxes related to meeting deep personal needs at different levels (physical, emotional, spiritual); the demands in the relationship with their business, (some demands are more tangible than others) and the intertwined life long commitment that being a member of a family and business brings.

The research aims to find out whether the responses of bloggers and public relations practitioners have any implication for the practice of public relations, and, whether blogging is an ethical tool to the public relations industry. This research studies the extent of the blogola (paid-post) practice and help understand why organizations still insist on practicing blogola despite the risk of negative public relations. The research also explores the ethical challenge encountered by the public relations industry in the digital age. The researchers evaluate whether new ethical guidelines are needed to resolve the issue of blogola. The researchers adopted the qualitative methodology, namely, the in-depth interview method. The informants are gathered using the convenience sampling, and, fifteen informants were extensively interviewed; being public relations practitioners, bloggers and consumers in Mauritius. The findings suggested that blogs are effective public relations tools to attract customers and boost sales. Deepening into the relationships between bloggers and public relations practitioners concluded that a friendly relationship is good for easy communication and for diversity of blog content. Concerning the ethical dilemma surrounding blogs and public relations, almost all informants agreed that paying bloggers for writing good reviews for the brand is not a violation, provided, the blogger is sincere and transparent about it. As long as the blogger reveals that he or she was compensated in any sort, it is tolerable. The question of new ethical guidelines is a must since social media has completely changed the way public relations work. Keywords: Public relations, bloggers, professional ethics, blogola, public relations practices.

ABSTRACTBackground: Market access stakeholders consider the adoption of Managed Entry Agreements (MEAs), however a clearly described methodology to quantify their implementation burden is not available in the public domain.Objective: To quantify the cost of implementing a performance-based MEA at the hospital level.Methods: The analysis involved a hypothetical one-off therapy targeting Acute Lymphoblastic Leukaemia. Data collection from five NHS Hospital Trusts in England captured costs by task, job band, personnel time and capital investment. We compared the administrative burden of the standard of care (SoC) to that of adopting the therapy with or without an MEA over 10 years.Findings: The 10-year cost for the activities required to support hospital payments for the target patient population in England varied as follows: for the SoC was £447,353, compared to £1,117,024 for the novel therapy with MEA, and £245,317 without MEA.Conclusions: The higher cost associated with the SoC compared to the novel therapy without an MEA, arises from the higher frequency of infusions requiring payments and the associated mandatory data capturing requirements for oncology therapies. The novel therapy with MEA presents the greatest burden due to increased frequency of monitoring in year one to compensate for the greater uncertainty in clinical data and to inform the performance-based reimbursement.

BJU InternationalVolume 113, Issue 4 p. 654-655 Translational Science What next for phosphodiesterase inhibitor failures? Michael G. Wyllie, Corresponding Author Michael G. Wyllie Plethora Solutions Ltd London, London, UK Correspondence: Michael G. Wyllie, Plethora Solutions Ltd, Stratton House, 3 Marshalls Close, Shenington, Oxford OX15 6ND, UK. e-mail: m.wyllie@globalpharma.co.ukSearch for more papers by this author Michael G. Wyllie, Corresponding Author Michael G. Wyllie Plethora Solutions Ltd London, London, UK Correspondence: Michael G. Wyllie, Plethora Solutions Ltd, Stratton House, 3 Marshalls Close, Shenington, Oxford OX15 6ND, UK. e-mail: m.wyllie@globalpharma.co.ukSearch for more papers by this author First published: 21 January 2014 https://doi.org/10.1111/bju.12636Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article. Volume113, Issue4April 2014Pages 654-655 RelatedInformation

What's known on the subject? and What does the study add? It is now accepted that both biological and psychological factors are important in the aetiology of premature ejaculation (PE). Of particular interest is the correlation between ejaculatory latency and penile sensory thresholds. Men with PE appear to have a heightened sensory response to penile stimulation and also generally exhibit other abnormal reflex pathways within the ejaculatory process, suggesting a link between penile hypersensitivity and PE. Considering these sensory differences, drugs that selectively produce some degree of penile desensitization or act within the afferent-efferent reflex could delay ejaculatory latency without adversely affecting the sensation of ejaculation. This review evaluates published clinical trial data for local anaesthetics used off-label in PE as well as novel topical agents in development. New analyses of the phase III data are presented for topical eutectic mixture for PE (TEMPE, also known as PSD502, Plethora Solutions Plc., London), a proprietary formulation of lidocaine and prilocaine in a metered-dose aerosol delivery system. • To review the published clinical trial data for local anaesthetics used off-label in premature ejaculation (PE), as well as novel topical agents in development. • To evaluate the safety and efficacy of topical eutectic mixture for PE (TEMPE) in subjects with PE and their sexual partners using all available phase III data. • Topical treatments can be applied as needed and systemic side-effects are unlikely. However, existing off-label topical treatments for PE have several disadvantages: they can be messy, interfere with spontaneity, and could cause numbness in the man or his partner. • Several novel topical agents are in development for the treatment of PE. TEMPE appears to be closest to approval. • TEMPE, applied 5 min before sexual intercourse (539 subjects) resulted in an increase in the geometric mean intra-vaginal ejaculatory time (IELT) from a baseline of 0.58 min to 3.17 min during 3 months of double-blind treatment; a 3.3-fold delay in ejaculation compared with placebo (P < 0.001). • IELT continued to increase further with continued use of TEMPE throughout the double-blind and open-label phases. • Treatment with TEMPE also resulted in marked improvements in subjective measures, e.g. ejaculatory control, sexual satisfaction and distress, with little or no evidence of systemic side-effects and minimal desensitization of the genitalia in subjects or their sexual partners. • The use of a topical agent could be an acceptable first-line option for PE, given the favourable risk/benefit ratio of these products. • Topical aerosol application of TEMPE may provide safe, effective, on-demand treatment for PE.

What's known on the subject? and What does the study add? Striant® SR is the only available buccal delivery system for testosterone replacement therapy. Previous pharmacokinetic studies have shown that Striant SR effectively produces physiological serum testosterone levels in hypogonadal men. Efficacy and safety data from previously unpublished studies over 2 years of continuous use indicate that Striant SR is effective long term in maintaining serum testosterone within a physiological range, is well tolerated and has a high level of patient acceptance. Striant® sustained-release (SR) is a mucoadhesive buccal tablet (30 mg testosterone, The Urology Company) that adheres to the gum surface in the mouth providing controlled- and sustained-release of testosterone over a 12-h dosing period, offering a unique and rational method of testosterone delivery. Striant SR is indicated for testosterone-replacement therapy (TRT) for male hypogonadism when testosterone deficiency has been confirmed by clinical features and biochemical tests. Pharmacokinetic studies have shown that testosterone is released from Striant SR in a manner similar to the normal daily rhythm of endogenous testosterone secretion, with serum levels rising rapidly after insertion and peak levels reached by the second 12-hourly dose with no accumulation over time. In clinical trials involving hypogonadal men receiving Striant SR for up to 2 years, mean serum testosterone levels have always remained within the normal range. Striant SR is well tolerated, with gum-related disorders (such as irritation, inflammation and gingivitis) and taste perversion being the most commonly reported adverse events, reported by 5.6-16.3% and 3.0-4.1% of patients, respectively. Once patients have become accustomed to it, Striant SR has a high level of patient acceptance. In a long-term study, 90% of patients rated the twice-daily dosing as acceptable, just under half preferred it to other forms of TRT that they have used and 96% found it to be cosmetically acceptable. There is no clinically significant risk of testosterone transfer from Striant SR, as any testosterone that may be present in the saliva when swallowed is subject to extensive first-pass hepatic metabolism. It is pertinent to note that the saliva of eugonadal men contains similar levels of endogenous testosterone. Buccal delivery is particularly suitable where easy and rapid reversal of treatment might be required (such as in late-onset hypogonadism) and where there is a need to avoid the potential for transfer of testosterone to women and young children.