Accountability in patenting of federally funded research

Bayh-Dole allows academic grantees to patent federally-funded research for purposes of promoting the commercialization of this research. To ensure commercialization goals are achieved, the Act requires grantees to report to funding agencies not only the existence of federally-funded patents but also utilization efforts they and their licensees/assignees are making. Although reporting is a cornerstone of accountability under Bayh-Dole, information about grantee compliance with reporting requirements is incomplete and dated. In fact, the last significant study of the question dates back to the late 1990s and analyzes only 633 patents. Since that time, concerns have emerged that federally-funded university patents are being asserted improperly against independent commercializers or even assigned to so-called “patent trolls.” This article provides fresh evidence indicating substantial under-reporting of the existence of federal funding in over 30,000 academic biomedical patents issued between 1980 to 2007. The article finds substantial under-reporting of federal funding even in the case of patents on FDA-approved drugs, which should presumably receive significant attention from universities. Grantees’ failure to report federal funding suggests similar, or even more significant, noncompliance with requirements to report utilization information. However, compliance with reporting requirements on utilization cannot be assessed because of secrecy associated with relevant government databases. Accordingly, the article makes a fresh argument that the Commerce Department, which has the requisite regulatory authority, work with funding agencies, to improve transparency. Greater transparency would not only motivate grantees to improve reporting but would also allow assessment of whether grantee patent management is actually achieving Bayh-Dole\u27s utilization goals

Flat-panel detectors: how much better are they?

Interventional and fluoroscopic imaging procedures for pediatric patients are becoming more prevalent because of the less-invasive nature of these procedures compared to alternatives such as surgery. Flat-panel X-ray detectors (FPD) for fluoroscopy are a new technology alternative to the image intensifier/TV (II/TV) digital system that has been in use for more than two decades. Two major FPD technologies have been implemented, based on indirect conversion of X-rays to light (using an X-ray scintillator) and then to proportional charge (using a photodiode), or direct conversion of X-rays into charge (using a semiconductor material) for signal acquisition and digitization. These detectors have proved very successful for high-exposure interventional procedures but lack the image quality of the II/TV system at the lowest exposure levels common in fluoroscopy. The benefits for FPD image quality include lack of geometric distortion, little or no veiling glare, a uniform response across the field-of-view, and improved ergonomics with better patient access. Better detective quantum efficiency indicates the possibility of reducing the patient dose in accordance with ALARA principles. However, first-generation FPD devices have been implemented with less than adequate acquisition flexibility (e.g., lack of tableside controls/information, inability to easily change protocols) and the presence of residual signals from previous exposures, and additional cost of equipment and long-term maintenance have been serious impediments to purchase and implementation. Technological advances of second generation and future hybrid FPD systems should solve many current issues. The answer to the question ‘how much better are they?–is ‘significantly better– and they are certainly worth consideration for replacement or new implementation of an imaging suite for pediatric fluoroscopy

Magnetic resonance imaging in patients with meningitis induced hearing loss

The aim of this multicentre study was to compare T1 with T2 weighted MRI scans of the labyrinth after meningitis and to investigate whether waiting with scanning improved the reliability of diagnosing an ongoing process such as cochlear osteogenesis. Forty-five patients were included who suffered from meningitis induced hearing loss (radiological imaging <1 year after meningitis). Twenty-one gadolinium enhanced T1 and 45 T2 weighted MRI scans were scored by two radiologists regarding the condition of the labyrinth. These radiological observations were compared with the condition of the cochlea as described during cochlear implantation. A higher percentage of agreement with surgery was found for T2 (both radiologists 73%) than for T1 weighted MRI scans (radiologist 1: 62%, radiologist 2: 67%), but this difference is not significant. There was no significant difference between early (0–3 months) and late (>3 months) scanning, showing that radiological imaging soon after meningitis allows early diagnosis without suffering from a lower agreement with surgical findings

Density Contrast Sedimentation Velocity for the Determination of Protein Partial-Specific Volumes

The partial-specific volume of proteins is an important thermodynamic parameter required for the interpretation of data in several biophysical disciplines. Building on recent advances in the use of density variation sedimentation velocity analytical ultracentrifugation for the determination of macromolecular partial-specific volumes, we have explored a direct global modeling approach describing the sedimentation boundaries in different solvents with a joint differential sedimentation coefficient distribution. This takes full advantage of the influence of different macromolecular buoyancy on both the spread and the velocity of the sedimentation boundary. It should lend itself well to the study of interacting macromolecules and/or heterogeneous samples in microgram quantities. Model applications to three protein samples studied in either H2O, or isotopically enriched H218O mixtures, indicate that partial-specific volumes can be determined with a statistical precision of better than 0.5%, provided signal/noise ratios of 50–100 can be achieved in the measurement of the macromolecular sedimentation velocity profiles. The approach is implemented in the global modeling software SEDPHAT

Effect of household-based drinking water chlorination on diarrhoea among children under five in Orissa, India: a double-blind randomised placebo-controlled trial.

BACKGROUND: Boiling, disinfecting, and filtering water within the home can improve the microbiological quality of drinking water among the hundreds of millions of people who rely on unsafe water supplies. However, the impact of these interventions on diarrhoea is unclear. Most studies using open trial designs have reported a protective effect on diarrhoea while blinded studies of household water treatment in low-income settings have found no such effect. However, none of those studies were powered to detect an impact among children under five and participants were followed-up over short periods of time. The aim of this study was to measure the effect of in-home water disinfection on diarrhoea among children under five. METHODS AND FINDINGS: We conducted a double-blind randomised controlled trial between November 2010 and December 2011. The study included 2,163 households and 2,986 children under five in rural and urban communities of Orissa, India. The intervention consisted of an intensive promotion campaign and free distribution of sodium dichloroisocyanurate (NaDCC) tablets during bi-monthly households visits. An independent evaluation team visited households monthly for one year to collect health data and water samples. The primary outcome was the longitudinal prevalence of diarrhoea (3-day point prevalence) among children aged under five. Weight-for-age was also measured at each visit to assess its potential as a proxy marker for diarrhoea. Adherence was monitored each month through caregiver's reports and the presence of residual free chlorine in the child's drinking water at the time of visit. On 20% of the total household visits, children's drinking water was assayed for thermotolerant coliforms (TTC), an indicator of faecal contamination. The primary analysis was on an intention-to-treat basis. Binomial regression with a log link function and robust standard errors was used to compare prevalence of diarrhoea between arms. We used generalised estimating equations to account for clustering at the household level. The impact of the intervention on weight-for-age z scores (WAZ) was analysed using random effect linear regression. Over the follow-up period, 84,391 child-days of observations were recorded, representing 88% of total possible child-days of observation. The longitudinal prevalence of diarrhoea among intervention children was 1.69% compared to 1.74% among controls. After adjusting for clustering within household, the prevalence ratio of the intervention to control was 0.95 (95% CI 0.79-1.13). The mean WAZ was similar among children of the intervention and control groups (-1.586 versus -1.589, respectively). Among intervention households, 51% reported their child's drinking water to be treated with the tablets at the time of visit, though only 32% of water samples tested positive for residual chlorine. Faecal contamination of drinking water was lower among intervention households than controls (geometric mean TTC count of 50 [95% CI 44-57] per 100 ml compared to 122 [95% CI 107-139] per 100 ml among controls [p<0.001] [n = 4,546]). CONCLUSIONS: Our study was designed to overcome the shortcomings of previous double-blinded trials of household water treatment in low-income settings. The sample size was larger, the follow-up period longer, both urban and rural populations were included, and adherence and water quality were monitored extensively over time. These results provide no evidence that the intervention was protective against diarrhoea. Low compliance and modest reduction in water contamination may have contributed to the lack of effect. However, our findings are consistent with other blinded studies of similar interventions and raise additional questions about the actual health impact of household water treatment under these conditions. TRIAL REGISTRATION: ClinicalTrials.govNCT01202383 Please see later in the article for the Editors' Summary

Use of complementary/alternative therapies by women with advanced-stage breast cancer

BACKGROUND: This study sought to describe the pattern of complementary/alternative medicine (CAM) use among a group of patients with advanced breast cancer, to examine the main reasons for their CAM use, to identify patient's information sources and their communication pattern with their physicians. METHODS: Face-to-face structured interviews of patients with advanced-stage breast cancer at a comprehensive oncology center. RESULTS: Seventy three percent of patients used CAM; relaxation/meditative techniques and herbal medicine were the most common. The most commonly cited primary reason for CAM use was to boost the immune system, the second, to treat cancer; however these reasons varied depending on specific CAM therapy. Friends or family members and mass media were common primary information source's about CAM. CONCLUSIONS: A high proportion of advanced-stage breast cancer patients used CAM. Discussion with doctors was high for ingested products. Mass media was a prominent source of patient information. Credible sources of CAM information for patients and physicians are needed

In Vivo, Multimodal Imaging of B Cell Distribution and Response to Antibody Immunotherapy in Mice

BACKGROUND: B cell depletion immunotherapy has been successfully employed to treat non-Hodgkin's lymphoma. In recent years, increasing attention has been directed towards also using B-cell depletion therapy as a treatment option in autoimmune disorders. However, it appears that the further development of these approaches will depend on a methodology to determine the relation of B-cell depletion to clinical response and how individual patients should be dosed. Thus far, patients have generally been followed by quantification of peripheral blood B cells, but it is not apparent that this measurement accurately reflects systemic B cell dynamics. METHODOLOGY/PRINCIPAL FINDINGS: Cellular imaging of the targeted population in vivo may provide significant insight towards effective therapy and a greater understanding of underlying disease mechanics. Superparamagnetic iron oxide (SPIO) nanoparticles in concert with near infrared (NIR) fluorescent dyes were used to label and track primary C57BL/6 B cells. Following antibody mediated B cell depletion (anti-CD79), NIR-only labeled cells were expeditiously cleared from the circulation and spleen. Interestingly, B cells labeled with both SPIO and NIR were not depleted in the spleen. CONCLUSIONS/SIGNIFICANCE: Whole body fluorescent tracking of B cells enabled noninvasive, longitudinal imaging of both the distribution and subsequent depletion of B lymphocytes in the spleen. Quantification of depletion revealed a greater than 40% decrease in splenic fluorescent signal-to-background ratio in antibody treated versus control mice. These data suggest that in vivo imaging can be used to follow B cell dynamics, but that the labeling method will need to be carefully chosen. SPIO labeling for tracking purposes, generally thought to be benign, appears to interfere with B cell functions and requires further examination

Facing others’ misfortune: Personal distress mediates the association between maladaptive emotion regulation and social avoidance

Previous research has linked the use of certain emotion regulation strategies to the vicarious experience of personal distress (PD) and empathic concern (EC). However, it has not been tested yet whether (1) vicarious PD is positively associated with maladaptive emotion regulation strategies, (2) vicarious EC is positively associated with adaptive emotion regulation strategies and whether (3) PD and EC mediate the link between emotion regulation and reports of approach/avoidance in response to a person in distress. To that aim, we assessed people’s reports of PD (i.e., anxious, troubled, and upset) and EC (i.e., concerned, sympathetic, and soft-hearted) in response to a video depicting a person in a threatening situation (n = 78). Afterwards, we assessed participants’ reports of avoidance and approach in regards to the character and their disposition to use maladaptive and adaptive emotion regulation strategies. Results showed that PD as well as EC were positively related to maladaptive strategies and negatively related to adaptive strategies, and that the association between maladaptive regulation strategies (i.e., rumination) and the willingness to avoid the person in distress was mediated by greater reports of PD. This study thus expands previous evidence on the relationship between maladaptive regulation strategies and affective empathy and provides novel insights about the main role that personal distress played in the association between maladaptive strategies and social avoidance