Linear position-sensitive x-ray detector incorporating a self-scanning photodiode array

A linear position-sensitive x-ray detector for x-ray spectroscopy and diffraction applications has been tested which can provide excellent spatial resolution, wide dynamic range and good sensitivity. The heart of the system is a self-scanning, photosensitive silicon diode array. It is interfaced via fiber optics to a thin layer of ZnS which fluoresces visible light upon absorption of x-radiation. The conversion to visible light and optical coupling provide several-fold gain in the efficiency of detection as compared to the direct detection of x-ray by the diode array. Equally important is that the array is protected from irreversible damage by high energy radiation, a limitation which previously hindered this application of silicon diode technology

Treatment as Prevention: Characterization of Partner Infections in the HIV Prevention Trials Network 052 Trial

HIV Prevention Trials Network (HPTN) 052 demonstrated that antiretroviral therapy (ART) prevents HIV transmission in serodiscordant couples. HIV from index-partner pairs was analyzed to determine the genetic linkage status of partner infections. Forty-six infections were classified as linked, indicating that the index was the likely source of the partner’s infection. Lack of viral suppression and higher index viral load were associated with linked infection. Eight linked infections were diagnosed after the index started ART: four near the time of ART initiation and four after ART failure. Linked infections were not observed when the index participant was stably suppressed on ART

Software Development Standard Processes (SDSP)

A JPL-created set of standard processes is to be used throughout the lifecycle of software development. These SDSPs cover a range of activities, from management and engineering activities, to assurance and support activities. These processes must be applied to software tasks per a prescribed set of procedures. JPL s Software Quality Improvement Project is currently working at the behest of the JPL Software Process Owner to ensure that all applicable software tasks follow these procedures. The SDSPs are captured as a set of 22 standards in JPL s software process domain. They were developed in-house at JPL by a number of Subject Matter Experts (SMEs) residing primarily within the Engineering and Science Directorate, but also from the Business Operations Directorate and Safety and Mission Success Directorate. These practices include not only currently performed best practices, but also JPL-desired future practices in key thrust areas like software architecting and software reuse analysis. Additionally, these SDSPs conform to many standards and requirements to which JPL projects are beholden

Key stakeholder perceptions about consent to participate in acute illness research: a rapid, systematic review to inform epi/pandemic research preparedness

Background A rigorous research response is required to inform clinical and public health decision-making during an epi/pandemic. However, the ethical conduct of such research, which often involves critically ill patients, may be complicated by the diminished capacity to consent and an imperative to initiate trial therapies within short time frames. Alternative approaches to taking prospective informed consent may therefore be used. We aimed to rapidly review evidence on key stakeholder (patients, their proxy decision-makers, clinicians and regulators) views concerning the acceptability of various approaches for obtaining consent relevant to pandemic-related acute illness research. Methods We conducted a rapid evidence review, using the Internet, database and hand-searching for English language empirical publications from 1996 to 2014 on stakeholder opinions of consent models (prospective informed, third-party, deferred, or waived) used in acute illness research. We excluded research on consent to treatment, screening, or other such procedures, non-emergency research and secondary studies. Papers were categorised, and data summarised using narrative synthesis. Results We screened 689 citations, reviewed 104 full-text articles and included 52. Just one paper related specifically to pandemic research. In other emergency research contexts potential research participants, clinicians and research staff found third-party, deferred, and waived consent to be acceptable as a means to feasibly conduct such research. Acceptability to potential participants was motivated by altruism, trust in the medical community, and perceived value in medical research and decreased as the perceived risks associated with participation increased. Discrepancies were observed in the acceptability of the concept and application or experience of alternative consent models. Patients accepted clinicians acting as proxy-decision makers, with preference for two decision makers as invasiveness of interventions increased. Research regulators were more cautious when approving studies conducted with alternative consent models; however, their views were generally under-represented. Conclusions Third-party, deferred, and waived consent models are broadly acceptable to potential participants, clinicians and/or researchers for emergency research. Further consultation with key stakeholders, particularly with regulators, and studies focused specifically on epi/pandemic research, are required. We highlight gaps and recommendations to inform set-up and protocol development for pandemic research and institutional review board processes

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Vesicle Targeting: Timed Release and Specificity for Leukocytes in Mice by Subcutaneous Injection

When unilamellar vesicles were administered subcutaneously in mice, the half-time for the destruction of the vesicles varied from 12 to 600 hours, depending on their composition. The vesicles tested consisted of distearoyl phosphatidylcholine, cholesterol, and certain sugar and amino-sugar derivatives of cholesterol. Vesicles with amino-sugar derivatives showed the greatest longevity and became localized with high specificity in aggregates of polymorphonuclear leukocytes. A substantial delay between the time that the vesicles broke open and the time that labels contained in the vesicles were excreted suggests that the vesicles undergo endocytosis before destruction

An Introduction to the Special issue - Housing in Hard Times: Marginality, Inequality and Class, with Kim McKee

‘Housing in Hard Times’ was the theme of the Housing Studies Association annual conference in April 2011. The papers featured in this special issue are drawn from that conference. They examine the uneven impact of economic change on housing policy and related areas, with reference to conceptual ideas pertaining to urban marginality, inequality and class. Whilst the empirical focus of the papers is the UK, their intellectual contribution represents an attempt to ‘bring class back in’ to the housing studies literature and encourage more critical, theoretically informed scholarship.PostprintNon peer reviewe