2016 Annual Impact Investor Survey

The sixth edition of the Annual Impact Investor Survey is based on an analysis of the activities of 158 of the world's leading impact investing organizations, including fund managers, foundations, banks, development finance institutions, family offices, pension funds, and insurance companies. The survey provides detailed insight into investor perceptions and a number of key market variables such as types of investors, the number and size of investments made, target returns, attitudes towards liquidity and responsible exits, and impact measurement practices. This "State of the Market" analysis explores how investments continue to be made across different geographies, a range of sectors, and multiple asset classes, signaling continued market growth and an increasing interest in impact investing opportunities. J.P. Morgan is an anchor sponsor of the 2016 survey. The study was also produced with support from the U.K. Government through the Department for International Development's Impact Programme

Advances in breast cancer treatment and prevention: preclinical studies on aromatase inhibitors and new selective estrogen receptor modulators (SERMs).

Intensive basic and clinical research over the past 20 years has yielded crucial molecular understanding into how estrogen and the estrogen receptor act to regulate breast cancer and has led to the development of more effective, less toxic, and safer hormonal therapy agents for breast cancer management and prevention. Selective potent aromatase inhibitors are now challenging the hitherto gold standard of hormonal therapy, the selective estrogen-receptor modulator tamoxifen. Furthermore, new selective estrogen-receptor modulators such as arzoxifene, currently under clinical development, offer the possibility of selecting one with a more ideal pharmacological profile for treatment and prevention of breast cancer. Two recent studies in preclinical model systems that evaluate mechanisms of action of these new drugs and suggestions about their optimal clinical use are discussed

Annual Impact Investor Survey 2016

The sixth edition of the Annual Impact Investor Survey is based on an analysis of the activities of 158 of the world's leading impact investing organizations, including fund managers, foundations, banks, development finance institutions, family offices, pension funds, and insurance companies.The survey provides detailed insight into investor perceptions and a number of key market variables such as types of investors, the number and size of investments made, target returns, attitudes towards liquidity and responsible exits, and impact measurement practices. This "State of the Market" analysis explores how investments continue to be made across different geographies, a range of sectors, and multiple asset classes, signaling continued market growth and an increasing interest in impact investing opportunities.J.P. Morgan is an anchor sponsor of the 2016 survey. The study was also produced with support from the U.K. Government through the Department for International Development's Impact Programme

Indication Alerts Intercept Drug Name Confusion Errors during Computerized Entry of Medication Orders

Background: Confusion between similar drug names is a common cause of potentially harmful medication errors. Interventions to prevent these errors at the point of prescribing have had limited success. The purpose of this study is to measure whether indication alerts at the time of computerized physician order entry (CPOE) can intercept drug name confusion errors. Methods and Findings: A retrospective observational study of alerts provided to prescribers in a public, tertiary hospital and ambulatory practice with medication orders placed using CPOE. Consecutive patients seen from April 2006 through February 2012 were eligible if a clinician received an indication alert during ordering. A total of 54,499 unique patients were included. The computerized decision support system prompted prescribers to enter indications when certain medications were ordered without a coded indication in the electronic problem list. Alerts required prescribers either to ignore them by clicking OK, to place a problem in the problem list, or to cancel the order. Main outcome was the proportion of indication alerts resulting in the interception of drug name confusion errors. Error interception was determined using an algorithm to identify instances in which an alert triggered, the initial medication order was not completed, and the same prescriber ordered a similar-sounding medication on the same patient within 5 minutes. Similarity was defined using standard text similarity measures. Two clinicians performed chart review of all cases to determine whether the first, non-completed medication order had a documented or non-documented, plausible indication for use. If either reviewer found a plausible indication, the case was not considered an error. We analyzed 127,458 alerts and identified 176 intercepted drug name confusion errors, an interception rate of 0.14±.01%. Conclusions: Indication alerts intercepted 1.4 drug name confusion errors per 1000 alerts. Institutions with CPOE should consider using indication prompts to intercept drug name confusion errors

Sub-100 nm gold nanomatryoshkas improve photo-thermal therapy efficacy in large and highly aggressive triple negative breast tumors

There is an unmet need for efficient near-infrared photothermal transducers for the treatment of highly aggressive cancers and large tumors where the penetration of light can be substantially reduced, and the intra-tumoral nanoparticle transport is restricted due to the presence of hypoxic or necrotic regions. We report the performance advantages obtained by sub 100 nm gold nanomatryushkas, comprising concentric gold–silica–gold layers compared to conventional ~ 150 nm silica core gold nanoshells for photothermal therapy of triple negative breast cancer. We demonstrate that a 33% reduction in silica–core–gold-shell nanoparticle size, while retaining near-infrared plasmon resonance, and keeping the nanoparticle surface charge constant, results in a four to five fold tumor accumulation of nanoparticles following equal dose of injected gold for both sizes. The survival time of mice bearing large (> 1000 mm3) and highly aggressive triple negative breast tumors is doubled for the nanomatryushka treatment group under identical photo-thermal therapy conditions. The higher absorption cross-section of a nanomatryoshka results in a higher efficiency of photonic to thermal energy conversion and coupled with 4–5 × accumulation within large tumors results in superior therapy efficacy

Self-perception and perceived parental perception in adolescent girls with anorexia nervosa

Negative self-perception is associated with poor outcomes in adults with anorexia nervosa (AN). Our study aimed to assess the association between the self-perception of female adolescents with AN and how these adolescents perceive the attitudes of their parents toward them on the severity and short-term outcome of their illness. For this purpose, we assessed 30 adolescent girls hospitalized with AN and 30 female controls. Self-perception and perceived parental attitudes were assessed using the Structural Analysis of Social Behavior (SASB), according to which self-perception is formed via close relations with significant others in early life. Patients with AN responded to the SASB and to questionnaires assessing eating disorder (ED) symptomatology and emotional distress at both admission and discharge. Controls were similarly assessed once. We found that patients with AN showed a more negative self-perception than controls. Negative self-perception was associated with negative perceptions of the mothers’ attitudes toward the girls. There was no between-group difference in the perceived perception of the fathers’ attitude to the girls. Self-perception and perceived parental attitudes were associated with the severity of ED symptoms and emotional distress. Finally, an improvement was found in self-perception and perceived maternal attitudes toward the girl from admission to discharge, alongside a decrease in the severity of ED symptoms and emotional distress. Self-perception at admission was associated with ED pathology and emotional distress at discharge. These findings suggest that self-perception and perceived parental attitudes toward the adolescent with AN may be associated with the severity of the illness and its short-term outcome

β1 integrin mediates an alternative survival pathway in breast cancer cells resistant to lapatinib

Abstract Introduction The overexpression of human epidermal growth factor receptor (HER)-2 in 20% of human breast cancers and its association with aggressive growth has led to widespread use of HER2-targeted therapies, such as trastuzumab (T) and lapatinib (L). Despite the success of these drugs, their efficacy is limited in patients whose tumors demonstrate de novo or acquired resistance to treatment. The β1 integrin resides on the membrane of the breast cancer cell, activating several elements of breast tumor progression including proliferation and survival. Methods We developed a panel of HER2-overexpressing cell lines resistant to L, T, and the potent LT combination through long-term exposure and validated these models in 3D culture. Parental and L/T/LT-resistant cells were subject to HER2 and β1 integrin inhibitors in 3D and monitored for 12 days, followed by quantification of colony number. Parallel experiments were conducted where cells were either stained for Ki-67 and Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) or harvested for protein and analyzed by immunoblot. Results were subjected to statistical testing using analysis of variance and linear contrasts, followed by adjustment with the Sidak method. Results Using multiple cell lines including BT474 and HCC1954, we reveal that in L and LT resistance, where phosphorylation of EGFR/HER1, HER2, and HER3 are strongly inhibited, kinases downstream of β1 integrin--including focal adhesion kinase (FAK) and Src--are up-regulated. Blockade of β1 by the antibody AIIB2 abrogates this up-regulation and functionally achieves significant growth inhibition of L and LT resistant cells in 3D, without dramatically affecting the parental cells. SiRNA against β1 as well as pharmacologic inhibition of FAK achieve the same growth inhibitory effect. In contrast, trastuzumab-resistant cells, which retain high levels of phosphorylated EGFR/HER1, HER2, and HER3, are only modestly growth-inhibited by AIIB2. Conclusions Our data suggest that HER2 activity, which is suppressed in resistance involving L but not T alone, dictates whether β1 mediates an alternative pathway driving resistance. Our findings justify clinical studies investigating the inhibition of β1 or its downstream signaling moieties as strategies to overcome acquired L and LT resistance

Bringing Molecular Tools into Environmental Resource Management: Untangling the Molecules to Policy Pathway

New advances in molecular biology can be invaluable tools in resource management, but they are best incorporated through a collaborative process with managers who understand the most pressing questions, practical limitations, and political constraints

Correlation between Quantitative PCR and Culture-Based Methods for Measuring Enterococcus spp. over Various Temporal Scales at Three California Marine Beaches

ABSTRACT Several studies have examined how fecal indicator bacteria (FIB) measurements compare between quantitative PCR (qPCR) and the culture methods it is intended to replace. Here, we extend those studies by examining the stability of that relationship within a beach, as affected by time of day and seasonal variations in source. Enterococcus spp. were quantified at three southern California beaches in the morning and afternoon using two qPCR assays, membrane filtration, and defined-substrate testing. While qPCR and culture-based measurements were consistently and significantly correlated, strength of the correlation varied both among and within beaches. Correlations were higher in the morning (0.45 < ρ < 0.74 [ P < 0.002]) than in the afternoon (0.18 < ρ < 0.45 [ P < 0.021]) and higher when the fecal contamination was concentrated (0.38 < ρ < 0.83 [ P < 0.001]) than when it was diffuse (0.19 < ρ < 0.34 [ P < 0.003]). The ratios of culture-based and qPCR results (CFU or most probable number [MPN] per calibrator cell equivalents [CCE]) also varied spatially and temporally. Ratios ranged between 0.04 and 0.85 CFU or MPN per CCE and were lowest at the beach affected by diffuse pollution. Patterns in the ratios over the course of the day were dissimilar across beaches, increasing with time at one beach and decreasing at another. The spatial and temporal variability we observed indicate that the empirical relationship between culture-based and qPCR results is not universal, even within a beach