Search

We aimed to determine the utility of FET PET in the management of indeterminate CNS lesions found on MRI. We performed a retrospective analysis of patients with FET PET at a single tertiary institution from 2011 to 2015. FET PET images were processed using usual methods and measurements taken including SUVmax, TBRmax, and analysis of dynamic series where available (Kipeak, Vdpeak, as well as tumor:background ratio for these variables). Correlation studies were performed using ANOVA between cohorts of high-grade histology, low-grade histology, and benign histology/stable on observation. Thirty-five patients were included, of whom 34 were suitable for analysis with median follow-up of 5 months. The positive predictive value of FET PET in this cohort was 83.3%. FET SUVmax differentiated between patients with high-grade (mean SUV 3.38, 95% CI 2.21-4.55), low-grade (1.88, 95% CI 1.33-2.43) and benign/observation (1.42, 95% CI 1.13-1.71) cohorts (p = 0.0003). Similarly, tumour to brain ratio was significant (p 0.0001). Kipeak distinguished between high grade and observation cohorts (p = 0.036), as did KiTBR (p = 0.025). Vd peak was not significantly different in these two cohorts (p = 0.057) but Vd TBR was (p = 0.041). In conclusion, FET PET demonstrated a high positive predictive value for glioma in patients with indeterminate brain lesions on MRI. The combination of negative FET and negative FDG PET scans may predict an indolent clinical course. Confirmatory trials are needed to establish the potential value of FET PET in guiding surgical management in this cohort.

This study documents that individual investors increase buy-initiated trades prior to ex-dividend days and increase sell-initiated trades after the ex-day. Institutions supply liquidity to individual investors by increasing their use of sell limit orders in the cum-dividend period and increasing their usage of buy limit orders in the ex-dividend period. Stocks that experience higher net purchases from individual investors operating through discount brokers in the cum-dividend period have lower ex-day returns in the order of 25 basis points. This difference is as large as 44 basis points for high yield securities. This contrasts with the average excess ex-day return of 24 basis points. The results indicate that individual investors play an influential role in ex-dividend pricing.

Using a sample of equity funds in China, we explore for the first time mutual funds that impose discretionary inflow restrictions (gates) on investors. Contrary to managers’ claim, we find no clear evidence that inflow gates protect investor interests. Despite their superior past performance, inflow-restricted funds’ subsequent returns decline dramatically. In addition, funds tilt toward a riskier investment strategy and deliver a negative risk-adjusted return when the gate is in place. Our analyses further reveal that, after announcing purchase limits on fund assets, funds attract extra flows and more retail investors. This is consistent with the scarcity principle in marketing. Overall, we suggest that leaving the fund gate ajar to investors appears to be more of a marketing ploy than a form of investor protection.

Superannuation fees have come under public scrutiny in recent years with the belief they are too high. We examine the determinants of fees and their relationship with fund performance. Superannuation funds with higher investment fees have higher allocations to asset classes that are riskier and are more expensive to manage. For-profit retail funds charge both higher investment fees and administration fees than other funds. Funds with higher investment fees do not generate higher returns than the least expensive funds. These findings suggest that superannuation members may not earn higher after-fee risk-adjusted returns by holding funds with higher fees.

We present the design and measured performance of a new carbon fiber strut design that is used in a cryogenically cooled truss for the Simons Observatory small aperture telescope. The truss consists of two aluminum 6061 rings separated by 24 struts. Each strut consists of a central carbon fiber tube fitted with two aluminum end caps. We tested the performance of the strut and truss by (i) cryogenically cycling and destructively pull-testing strut samples, (ii) non-destructively pull-testing the final truss, and (iii) measuring the thermal conductivity of the carbon fiber tubes. We found that the strut strength is limited by the mounting fasteners and the strut end caps, not the epoxy adhesive or the carbon fiber tube. This result is consistent with our numerical predictions. Our thermal measurements suggest that the conductive heat load through the struts (from 4 to 1 K) will be less than 1 mW. This strut design may be a promising candidate for use in other cryogenic support structures.

Using daily hedonic housing price index for five Australian capital cities, we document a negative relationship between prior COVID-19 cases and daily housing returns. Specifically, the daily housing return drops by 0.35 basis points or 1.26 percentage points annually for every doubling of newly confirmed COVID-19 cases in a state. We also examine the effect of government lockdown orders on housing returns and find insignificant results. These findings are robust under alternative pandemic proxies such as total active COVID-19 cases and other model specifications. Overall, our paper contributes to the literature on the geographic spread of pandemics and real estate prices.

Background Glioblastoma is an uncommon but highly aggressive type of brain tumour. Significant gains have been achieved in the molecular understanding and the pathogenesis of glioblastomas, however clinical improvements are difficult to obtain for many reasons. The current standard of care involves maximal safe surgical resection followed by chemoradiation and then adjuvant chemotherapy European Organisation for Research and Treatment of Cancer and the NCIC Clinical Trials Group (EORTC-NCIC) protocol with a median survival of 14.6 months. Successive phase III international randomised controlled studies have failed to significantly demonstrate survival advantage with newer drugs. Epidermal growth factor receptor (EGFR) is observed to be aberrant in 30% to 60% of glioblastomas. The receptor aberrancy is driven by abnormal gene amplification, receptor mutation, or both, in particular the extracellular vIII domain. EGFR abnormalities are common in solid tumours, and the advent of anti-EGFR therapies in non-small cell lung cancer and colorectal adenocarcinomas have greatly improved clinical outcomes. Anti-EGFR therapies have been investigated amongst glioblastomas, however questions remain about its ongoing role in glioblastoma management. This review aimed to report on the available evidence to date and perform a systematic analysis on the risks and benefits of use of anti-EGFR therapies in glioblastomas. Objectives To evaluate the efficacy and harms of anti-EGFR therapies for glioblastoma in adults. Search methods We searched CENTRAL, MEDLINE, Embase, EBM Reviews databases, with supplementary handsearches to identify all available and relevant studies to 20 April 2020. Selection criteria All randomised controlled trials (RCTs) using anti-EGFR therapies in adults with glioblastoma were eligible for inclusion. Anti-EGFR therapies included tyrosine kinase inhibitors, monoclonal antibodies, or vaccines. The comparison included investigational product added to standard of care versus standard of care or placebo, or investigational product against standard of care or placebo. Data collection and analysis The authorship team screened the search results and recorded the extracted data for analysis. We used standard Cochrane methodology to performed quantitative meta-analysis if two or more studies had appropriate and available data. Otherwise, we conducted a qualitative and descriptive analysis. We used the GRADE system to rate the certainty of the evidence. The analysis was performed along the two clinical settings: first-line (after surgery) and recurrent disease (after failure of first line treatment). Where information was available, we documented overall survival, progression-free survival, adverse events, and quality of life data from eligible studies. Main results The combined searches initially identified 912 records (after removal of duplicates), and further screening resulted in 19 records for full consideration. We identified nine eligible studies for inclusion in the review. There were three first-line studies and six recurrent studies. Five studies used tyrosine kinase inhibitors (TKIs); two studies used monoclonal antibodies; and two studies used targeted vaccines. More recent studies presented greater detail in the conduct of their studies and thus had a lower risk of bias. We observed no evidence benefit in overall survival with the use of anti-EGFR therapy in the first-line or recurrent setting (hazard ratio (HR) 0.89, 95% confidence interval (CI) 0.76 to 1.04; 3 RCTs, 1000 participants, moderate-certainty evidence; and HR 0.79, 95% CI 0.51 to 1.21, 4 RCTs, 489 participants, low-certainty evidence, respectively). All the interventions were generally well tolerated with low-certainty evidence for lymphopenia (odds ratio (OR) 0.97, 95% CI 0.19 to 4.81; 4 RCTs, 1146 participants), neutropenia (OR 1.29, 95% CI 0.82 to 2.03; 4 RCTs, 1146 participants), and thrombocytopenia (OR 3.69, 95% CI 0.51 to 26.51; 4 RCTs, 1146 participants). A notable toxicity relates to ABT-414, where significant ocular issues were detected. The addition of anti-EGFR therapy showed no evidence of an increase in progression-free survival (PFS) in the first-line setting (HR 0.94, 95% CI 0.81 to 1.10; 2 RCTs, 894 participants, low-certainty evidence). In the recurrent setting, there was an increase in PFS with the use of anti-EGFR therapy (HR 0.75, 95% CI 0.58 to 0.96, 3 RCTs, 275 participants, low-certainty evidence). The available quality of life assessment data showed that anti-EGFR therapies were neither detrimental or beneficial when compared to standard care (not estimable). Authors' conclusions In summary, there is no evidence of a demonstrable overall survival benefit with the addition of anti-EGFR therapy in first-line and recurrent glioblastomas. Newer drugs that are specially designed for glioblastoma targets may raise the possibility of success in this population, but data are lacking at present. Future studies should be more selective in pursuing people displaying specific EGFR targets.

Bacterial resistance to antibiotics is a growing problem that is projected to cause more deaths than cancer in 2050. Consequently, novel antibiotics are urgently needed. Since more than half of the available antibiotics target the bacterial ribosomes, proteins that are involved in protein synthesis are thus prime targets for the development of novel antibiotics. However, experimental identification of these potential antibiotic target proteins can be labor-intensive and challenging, as these proteins are likely to be poorly characterized and specific to few bacteria. In order to identify these novel proteins, we established a Large-Scale Transcriptomic Analysis Pipeline in Crowd (LSTrAP-Crowd), where 285 individuals processed 26 terabytes of RNA-sequencing data of the 17 most notorious bacterial pathogens. In total, the crowd processed 26,269 RNA-seq experiments and used the data to construct gene co-expression networks, which were used to identify more than a hundred uncharacterized genes that were transcriptionally associated with protein synthesis. We provide the identity of these genes together with the processed gene expression data. The data can be used to identify other vulnerabilities or bacteria, while our approach demonstrates how the processing of gene expression data can be easily crowdsourced.

Governments utilize home ownership schemes for the dual purpose of alleviating housing affordability and stimulating housing construction. This paper studies how the housing market responds to assistance policies by exploiting a natural experiment in Sydney, Australia, where buyers of new homes priced up to $600,000 were eligible for government subsidies between July 2010 and June 2012. We find this policy causes large distortions to the sales volume, price level, as well as area size of home transactions. Specifically, we find a large bunching just below the threshold price of $600,000, over 8 times of counterfactual density. This large bunching is from both buyers moving down the price range as well as new entrants attracted to the market by the policy. We also find new homes just below the threshold are associated with an overpricing of about $3,000, offsetting up to 56% of the received benefit. Further, we find homes are about 25% smaller in size than comparable homes in prior periods. Last, we document a wealth effect generated by these housing subsidies, where neighborhoods that receive more housing subsidies increase their new car purchases. Overall, our study sheds light on the effectiveness and externalities of housing stimulus in the form of subsidies to improve homeownership.

The COVID-19 pandemic has triggered an unprecedented crisis in the tourism industry. We study the impact of COVID-19 on global Airbnb booking activity regarding three factors: the initial Wuhan lockdown, local COVID-19 cases, and local lockdowns. Using reviews and cancellations as proxies for Airbnb bookings, we find that local lockdowns result in a 57.8% fall in global booking activities, with an 8.8% fall after the Wuhan lockdown. Every doubling of newly infected cases is associated with a 4.16% fall in bookings. The sensitivity of bookings to COVID-19 decreases with geographic distance to Wuhan, and increases with government stringency of lockdown policies as well as human mobility within a market. Using London, United Kingdom as a case study, we find private rooms experience over 20% more cancellations than entire homes, consistent with host fears of infection. On the supply side, we find stable listings volume and lower booking price. Hosts charge an infection risk premium of 5.2% for letting private rooms relative to entire homes.We also document hosts adopt a dynamic pricing strategy where dates in the near future have deeper discounts than those in more distant future, and professional hosts adjust prices to local COVID-19 cases more aggressively than non-professionals. Our study provides insights for hosts and policymakers to formulate recovery plans in a post COVID-19 economy.

BACKGROUND: Liquid biopsy for plasma circulating tumor DNA (ctDNA) next-generation sequencing (NGS) is commercially available and increasingly adopted in clinical practice despite a paucity of prospective data to support its use. METHODS: Patients with advanced lung cancers who had no known oncogenic driver or developed resistance to current targeted therapy (n = 210) underwent plasma NGS, targeting 21 genes. A subset of patients had concurrent tissue NGS testing using a 468-gene panel (n = 106). Oncogenic driver detection, test turnaround time (TAT), concordance, and treatment response guided by plasma NGS were measured. All statistical tests were two-sided. RESULTS: Somatic mutations were detected in 64.3% (135/210) of patients. ctDNA detection was lower in patients who were on systemic therapy at the time of plasma collection compared with those who were not (30/70, 42.9% vs 105/140, 75.0%; OR = 0.26, 95% CI = 0.1 to 0.5, P

Inflammation and coagulation are two intertwined pathways with evolutionary ties being traced back to the hemocyte, a single cell type in invertebrates that has functions in both the inflammatory and coagulation pathways. These systems have functioned together throughout evolution to provide a solid defence against infection, damaged cells and irritants. While these systems work in harmony the majority of the time, they can also become dysregulated or corrupted by tumours, enhancing tumour proliferation, invasion, dissemination and survival. This review aims to give a brief overview of how these systems work in harmony and how dysregulation of these systems aids in the development and progression of cancer, using glioma as an example.

© 2017 Elsevier B.V. Bitcoin is defined as digital money within a decentralized peer-to-peer payment network. It is a hybrid between fiat currency and commodity currency without intrinsic value and independent of any government or monetary authority. This paper analyses the question of whether Bitcoin is a medium of exchange or an asset and more specifically, what is its current usage and what usage will prevail in the future given its characteristics. We analyse the statistical properties of Bitcoin and find that it is uncorrelated with traditional asset classes such as stocks, bonds and commodities both in normal times and in periods of financial turmoil. The analysis of transaction data of Bitcoin accounts shows that Bitcoins are mainly used as a speculative investment and not as an alternative currency and medium of exchange.

In a seminal study, Elton and Gruber (1970) argue that ex-dividend day pricing can be used to infer the marginal tax rates of shareholders. If this view is correct, managers of individual firms would be provided with information of relevance to major financing and distribution decisions. We examine ex-dividend day pricing for individual firms and ask whether their CFOs could use the history of a firm’s ex-dividend price-drop to dividend ratios to infer reasonable estimates of their shareholders’ marginal tax rates. We use TAQ data for 1,124 US firms that have at least 30 ex-dividend days during a sample period from August 1993 to October 2012. Our results show that ex-dividend day pricing is so noisy as to prohibit sensible estimates of shareholders’ marginal tax rates. In addition, the results indicate that drop-off ratios generally lie within transaction cost boundaries, consistent with a limits to arbitrage transactions’ cost explanation provided by Kalay (1982).

Objectives: This study aimed to describe the longitudinal thromboembolism (TE) risk relative to the natural history of disease and clinical course of ROS1 rearranged non-small cell lung cancer (NSCLC). Materials and Methods Cases of ROS1-rearranged NSCLC from six Australian hospitals were pooled and evaluated for incidence, timing, predictors and outcomes of venous or arterial TE, as well as objective response rate (ORR) to active therapy and overall survival (OS). Results Of 42 patients recruited, 20 (48%) experienced TE; one (2%) arterial, 13 (31%) a pulmonary emboli (PE), and 12 (29%) a deep vein thrombosis. Among those with TE, six (30%) experienced multiple events, three as concurrent and three as recurrent diagnoses. The cumulative incidence of TE over time, adjusted for death as a competing risk factor, approached 50%. TE occurred prior to, during and post the peri-diagnostic period and occurred irrespective of treatment strategy. A thrombophilia was identified in n = 3/10 (30%) cases screened: in two factor V Leiden and in one anti-thrombin III (ATIII) deficiency. Median OS was 21.3 months in those with TE vs. 28.8 months in those without; hazard ratio 1.16 (95%CI 0.43–3.15). Respective ORR to first-line therapy with TE was 50% vs. 44% without TE in the chemotherapy arm and 67% vs. 50% in the targeted therapy arm. Conclusion In the rare cancer subtype, ROS1, these real-world data demonstrate sustained TE risk beyond the diagnostic period irrespective of therapeutic strategy. High incidence of PE, concurrent TE, and recurrent TE warrant validation in larger cohorts. Consideration of primary thromboprophylaxis in ROS1 populations is recommended.

Background To compare outcomes of high-risk human papilloma virus-related oropharyngeal squamous cell carcinoma (HPV OPSCC) treated with modern radiation treatment (RT) and daily image-guidance, staged with the 7th versus the 8th Edition (Ed) Union for International Cancer Control (UICC)/American Joint Committee on Cancer (AJCC) TNM staging systems. Methods All eligible patients with HPV OPSCC treated definitively over a 10-year period (2007–2016) at a single institution were included. Protocols consisting of either RT or chemo-radiation (CRT) (weekly cisplatin or cetuximab) +/− neoadjuvant chemotherapy for those with bulky disease were used. All patients were Fluorine-18-deoxyglucose positron emission tomography (FDG-PET) staged at baseline and at intervals for up to 2 years post-treatment. Patients received parotid-sparing intensity modulated or volumetric modulated arc therapy with simultaneous integrated boost to either 70Gy in 35 fractions or 66Gy in 30 fractions. The overall survival (OS) was determined for each stage using the 7th Ed and subsequently with the updated 8th Ed staging system. Results One hundred fifty-three patients were analysed. Patient stage groupings varied between the 7th and 8th Eds respectively; Stage I (0.7% vs 64.7%), Stage II (8.5% vs 22.2%), stage III (21.6% vs 12.4%) and stage IV (69.3% vs 0.7%). In the 7th Ed, the 5 year probability of OS for stages I to III was 90%, versus stage IV 85.5%. There was no statistically significant difference between the staging groups (p = 0.85). In the 8th Ed there was a statistically significant difference in 5 year OS for stage I and stage II disease (96.9% vs 77.1% respectively; p

This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: To evaluate the efficacy and harms of anti‐ therapies for glioblastoma.

This paper examines how sentiment affects homebuyers’ housing transaction decisions with a focus on auction sales. Utilizing housing transaction data in Sydney from 2000 to 2014, we find that transaction prices are significantly higher for auction sales compared with private sales, consistent with the notion of a “winner’s curse.” Four sentiment proxies, including three weather-based sentiment proxies and a survey-based sentiment index, are used to derive novel measures of sentiment, revealing that higher sentiment is associated with higher transaction prices, particularly for auction sales. Moreover, sentiment boosts sale prices particularly when the housing market is in boom; however, investors are not more prone to sentiment bias than are owner-occupiers. Sentiment exhibits an asymmetric effect in that low sentiment dampens price to a greater extent compared with the price-boosting effect of high sentiment. Our result is robust to using national sport events as sentiment shocks, selection bias, and participation constraints. Potential mechanisms include present-biased preferences and sentiment-related projection bias. Overall, our evidence sheds light on the role of sentiment in housing market decisions. This paper was accepted by Tyler Shumway, finance.

Institutional brokerage rates have been in decline. We investigate whether this reduction has coincided with a fall in benefits provided by brokers to institutional asset managers. We use trade packages from both active and passive equity funds from 1995 to 2001 and active equity funds from 2002 to 2010. We find that later period active funds recoup a combined 1.75 basis point benefit (from price impact cost recovery and short-term alpha) per basis point of brokerage cost. Later period active investors saw improved trade price impact and shorter-term alpha net benefits, relative to earlier period active investors. These results are robust after controlling for trade characteristics and cross-sectional variation over time. Our findings suggest that brokers innovate to provide valuable services in the subsequent, lower brokerage environment.

An effective portfolio disclosure regime must balance both its costs and benefits across the entire financial services industry. This study examines a number of disclosure regimes with respect to accuracy and susceptibility to copycat behaviour in an environment absent of mandatory disclosure. We find that periodic portfolio disclosure tends to underestimate true excess performance as well as idiosyncratic risk in top-quartile fund managers, with longer inter-reporting intervals tending to result in greater differences. Copycat funds following the disclosed holdings of top-tier managers significantly underperform, while copycats following bottom-tier managers significantly outperform. Our findings suggest that periodic reporting at monthly intervals or longer would not affect fund alpha generation.

Background: Targeted therapies [interferon (IFN), vascular endothelial growth factor (VEGF) inhibitors, and somatostatin analogs (SSA)] have become an integral part of the neuroendocrine tumor (NET) treatment paradigm. We systematically reviewed the available literature to assess the overall beneficial and negative effects of targeted therapy on progression-free survival (PFS), overall survival (OS), response rate (RR), and toxicity. Methods: Randomized controlled trials (RCT) were identified from MEDLINE, Embase, other major databases, and an electronic search of major conferences. Abstract review, quality assessment, and data abstraction were performed independently by 2 investigators. Meta-analyses were conducted using the generic inverse variance method with a random-effects model, with studies pooled according to drug class and/or control arm for clinical homogeneity. Results: Fifteen RCT [SSA, n = 2; mammalian target of rapamycin (mTOR)/VEGF inhibitors, n = 4; IFN, n = 3; targeted therapy added to everolimus, n = 2, and other, n = 4] investigating 2,790 patients were included. Overall, targeted agents improved PFS (HR 0.54; 95% CI 0.40-0.73) but not OS (HR 0.86; 95% CI 0.72-1.01). SSA improved PFS (HR 0.41; 95% CI 0.29-0.58) but not OS (HR 1.00; 95% CI 0.58-1.74). mTOR/VEGF inhibitors improved PFS (HR 0.48; 95% CI 0.32-0.72) but not OS (HR 0.82; 95% CI 0.58-1.17). Targeted therapies added to everolimus or IFN did not improve either PFS or OS. The RR overall was improved (OR 2.85; 95% CI 1.77-4.59) but toxicity was increased (meta-analysis not performed). Conclusions: The addition of targeted therapies improves PFS but not OS in NET. The evidence is strongest for VEGF inhibitors and SSA. There is an ongoing need for well-designed RCT to inform the optimal use of targeted therapies in NET.

Adrenocortical carcinoma is a rare cancer, with estimate population incidence of 0.7–2.0 cases per 1 million each year. It also carries poor prognosis with estimated 5-year survival of less than 15% of those with metastatic disease and has a poor response to cytotoxic treatment. A randomized controlled trial published in 2012 by Fassnacht et al. demonstrated improved progression-free survival with first-line etoposide-doxirubicin-cisplatin-mitotane (EDP-M) compared to first-line streptozocin–mitotane in patients with stage III–IV disease. We report a case of a 25-year-old female diagnosed with adrenocortical carcinoma with liver and lung metastases treated with adjuvant EDP-M chemotherapy. During her treatment, the patient experienced ongoing significant liver-associated burden of disease, which prompted a trial of trans-hepatic arterial chemoembolization with doxorubicin and mitomycin. The patient subsequently experienced complete remission of disease at 18 months with no fludeoxyglucose (FDG) avid lesions on PET/CT.

We unite investment by speculators and tech-savvy investors with a heterogeneous agent model. While speculators seek to profit from extrapolating the price trends, tech-savvy investors trade based on the prospective value of Bitcoin, which is a function of factors that capture the market demand and technical supply of Bitcoin. Estimating the structural model, we find the coexistence of speculators and tech-savvy investors in the Bitcoin market. We further show that, regardless of the market states, tech-savvy investors consistently buy (sell) Bitcoin when its price goes below (above) the prospective value. However, speculators follow a momentum trading strategy in the high-market-volatility regime and switch to a contrarian strategy in the low-market-volatility regime. Our finding suggests that a significant fraction of tech-savvy investors value the potential of Bitcoin as an innovative technology. Incorporating heterogeneous investors yields better in-sample estimation efficiency and out-of-sample forecasting precision than models that consider only speculators or tech-savvy investors.

Quad-copters are the premier platform for data collection tasks, yet their ability to collect data in indoor narrow spaces is severely compromised due to their huge size when carrying heavy sensors. In this letter, we study a bi-copter UAV configuration that has similar levels of versatility and improves the compactness or efficiency at the same time. Such an arrangement allows for the preservation of propeller size, meaning that we can effectively reduce the horizontal width of the UAV while still maintains the same payload capacity. Furthermore, pitch, roll and yaw control can also be achieved through mechanically simple means as well, increasing reliability and precision. We also found that the Gemini platform is the most power-efficient yet practical solution for indoor applications among all the twelve common UAV configurations. This letter will detail the entire process of creating the platform from picking the ideal propeller through aerodynamic analysis, system design, optimization, implementation, control, and real flight tests that demonstrate its ability to function seamlessly.

Background: Studies suggest an increasing occur rence of atypical femoral fractures with the use of bisphosphonates. Objective: T o examine whether the use of bisphosphonates increases the risk for atypical fractures. Design: S ystematic review and meta-analysis. Data Sources: Literature searc h of MEDLINE, Embase and Cochrane CENTRAL (1948–June 2013). Review Methods: Selection criteria: (i) randomized controlled trial or an observational study, (ii) evaluated bisphosphonate therapy versus no treatment and (iii) reported an incidence of subtrochanteric or diaphyseal fracture individually, or a composite of both. Two independent investigators completed study selection, data extraction and validity assessment. The Cochrane Risk of Bias Tool was used to assess the quality of included studies. Results: T en (n = 658 497) studies were included in the meta-analysis whic h demonstrated a statistically significant increased risk of subtrochanteric or diaphyseal fracture with bisphosphonate use [adjusted odds ratios (AOR) = 1.99, 95% confidence intervals (CI)= 1.28–3.10] with I 2 = 84.3% (95% CI = 73.5%–89.5%) and Egger P = 0.01. Subtrochanteric fractures showed an AOR = 2.71 (95% CI = 1.86–3.95) with I 2 = 83.6% (95% CI = 64.3%–90.3%) and Egger’s P = 2.29. Diaphyseal fractures had an AOR = 2.06 (95% CI = 1.70–2.50), I 2 = 29.7% (95% CI = 0%–73.7%) and Egger’s P = 1.22. Conclusion: R esults suggest there is an increased risk for atypical fractures associated with bisphosphonates and raises awareness to the potential complications related with bisphosphonates. These findings warrant the comprehensive evaluation of patients before initiating bisphosphonate therapy and highlights the need for additional medical decision analyses in future studies to compare the benefit over potential harms of bisphosphonate therapy.

Purpose: Evidence-based practice (EBP) is an essential component of good quality, patient-centered health care. This requires practitioners to acquire EBP skills and knowledge during undergraduate and continuing education. Evidence-based practice education exists in a range of health care disciplines, including optometry. Evidence-based practice education, however, depends on relevant skills and knowledge in educators. Courses and workshops exist for the development of EBP teaching skills in some areas of health care but not in optometry. Here, we describe a pilot workshop designed to enhance the teaching of EBP and to investigate the perspectives of optometric educators on EBP including their attitudes and perceived barriers to EBP and its teaching.\ud \ud Methods: Twenty-seven optometric educators including 8 facilitators participated. Of these, 14 were academics (including the 8 facilitators) and 13 were practitioners. Evidence-based practice attitudes were assessed using the Evidence-Based Practice Attitude Scale-50 with appropriate modifications for optometry. Workshop design incorporated strategies to trigger discussion among participants. A nominal group technique was used to identify, prioritize, and reach consensus on barriers to EBP.\ud \ud Results: Although some participants expressed reservations about EBP, a common understanding of the contemporary definition of EBP emerged in educators. Thirty-five barriers to EBP were identified; “time” was selected in the top five barriers by most participants and attracted the highest total score, well above any other barrier (negative attitude to EBP, volume of evidence, integration with clinical practice, and lack of lifelong learning mind-set). Attitudes toward EBP were generally positive and negatively correlated with age and time since graduation, respectively.\ud \ud Conclusions: A group of optometrists and academics new to implementing education in EBP displayed positive attitudes to EBP but considered that its application and teaching could be significantly hindered by a lack of time to access and appraise the large volume of available research evidence in the field of eye care.

Cardiac tamponade complicating malignant pericardial effusion from non-small cell lung cancer (NSCLC) is generally associated with extremely poor prognosis. With improved systemic chemotherapy and molecular targeted therapy for NSCLC in recent years, the prognosis of such patients and the value of invasive cardiothoracic surgery in this setting have not been adequately examined. We report outcomes from a contemporary case series of eight patients who presented with malignant cardiac tamponade due to NSCLC to an Australian academic medical institution over an 18 months period. Two cases of cardiac tamponade were de novo presentations of NSCLC and six cases were presentations following previous therapy for NSCLC. The median survival was 4.5 months with a range between 9 days to alive beyond 17 months. The two longest survivors are still receiving active therapy at 17 and 15 months after invasive surgical pericardial window respectively. One survivor had a histological subtype of large cell neuroendocrine carcinoma and the other received targeted therapy for epidermal growth factor receptor mutation. These results support the consideration of active surgical palliation to treating this oncological emergency complicating NSCLC, including the use of urgent drainage, surgical creation of pericardial window followed by appropriate systemic therapy in suitably fit patients.

Human epidermal growth factor 2 (HER2, ERBB2) mutations in lung cancers are oncogenic drivers that respond to HER2 targeted therapies. Little is known about the sensitivity of subtypes of HER2 mutant lung cancers to targeted agents. We present a patient with HER2 mutant lung cancer with a 12 base pair insertion YVMA (p.A775_G776insYVMA), who had a long natural history and durable partial response to afatinib. We demonstrate that afatinib has activity in patients with HER2 mutant lung cancers with exon 20 YVMA insertions, the most common variant.

In theoretical models of limit order books populated with liquidity traders there is a link between order aggressiveness, spreads, and the cost of waiting for execution. We directly test these models using an experimental setting where waiting time is important for traders, namely the ex-dividend day. Consistent with these models, we find that order placement is more aggressive before stocks begin trading ex-dividend. Stocks with higher expected costs of delaying execution experience larger declines in order aggressiveness from the cum-day to the ex-day. Waiting costs also impact effective bid-ask spreads, which fall on the cum-day before rising on the ex-day. © 2014 Elsevier B.V.

The returns to housing are particularly important because this asset class makes up such a large fraction of household wealth. Yet they are not straightforward to calculate given both the heterogeneity in homes and the fact they sell only infrequently. We outline a methodology for constructing the excess returns to housing at a disaggregated level, essentially that of the individual home. Our approach explicitly takes account of the inherent risk in homeownership with regard to the capital gain or loss component of housing returns. This approach is applied to a rich data set for Sydney, Australia, from 2003Q1 to 2011Q2. Our findings indicate that the returns to housing are on average quite weak though they exhibit significant diversity across dwelling types and regions. Excess returns are also strongly influenced by assumptions regarding the level of risk aversion. © 2014 American Real Estate and Urban Economics Association.

We measure the impact of murders on prices and rents of homes in Sydney. We find that housing prices fall by 3.9 per cent for homes within 0.2 miles of the murder in the year following the murder, and weaker results in the second year after a murder. We do not find any effects of murders on rents. Higher media coverage and being located closer to the murder (within 0.1 mile) have no additional effect on prices. Taken together, our findings suggest that proximity to a murder affects nearby property prices, particularly in the first year after the incident. © 2014 Economic Society of Australia.

© 2014 Michael G. Foster School of Business, University of Washington. We study the informativeness of trades via discount and full-service retail brokers. We find that trades via full-service retail brokers are statistically and economically more informative than are trades via discount retail brokers. This finding holds in every year over the 12-year sample period and in various subsamples. We also find that past returns, volatility, and news announcements positively relate to the net volume of discount retail brokers, but these variables are unrelated to the net volume of full-service retail brokers. Our results suggest that broker type selection bias is an important consideration in studying individual investors' trades.

© 2014 AFAANZ. Emulation funds are a potentially cost-effective way for multimanager funds to improve their investment performance by delaying and netting trade signals from underlying managers. We develop a model to represent the expected sources of differential performance in an emulation fund relative to its underlying multimanager portfolio. The model formalises the expected interaction between potential savings and opportunity costs and allows us to observe complexities in the emulation process that are hidden without a benchmark. Finally, the functional representation of the model allows sensitivity analysis of the emulation fund to key parameters and enables us to determine theoretically optimal lag periods.

This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: To assess the efficacy and safety of the use of anti‐angiogenic agents (VEGF inhibitors) in the adjuvant setting after resection in patients diagnosed with resectable colorectal cancer. This would permit a summary of the safety and effectiveness of anti‐VEGF therapies overall, as well as in pre‐planned prognostic subgroups, and identify areas where further research could be directed.

Introduction The study aims to report outcomes for patients treated using intensity-modulated radiotherapy (IMRT) with simultaneous-integrated boost and weekly cisplatin for American Joint Committee on Cancer stage III/IV mucosal head and neck squamous cell carcinomas (HNSCCs). Methods Records for 67 patients treated definitively with IMRT for HNSCC were reviewed. By including only those treated with weekly cisplatin, 45 patients were eligible for analysis. Treatment outcomes, effect of patient, tumour and treatment characteristics on disease recurrence were analysed. Results All patients completed IMRT to 7000 cGy in 35 fractions, with concurrent weekly cisplatin 40 mg/m2 (median 6 cycles). Median follow-up was 28 months for living patients. Two-year loco-regional recurrence-free, metastasis-free and overall survival were 85.4, 81.0 and 87.4%, respectively. Local recurrence occurred in three patients, and distant recurrence in eight patients. Conclusions Our results show efficacy of IMRT and weekly cisplatin in the treatment of stage III/IV HNSCC at our institution with respect to loco-regional control.