Family Resources Survey: United Kingdom 2010/11

The Family Resources Survey collects information on the incomes and circumstances of private households in the United Kingdom. It has been running since October 1992. This report summarises the results for the 2010/11 full survey year in which approximately 25,000 households were interviewed. The report is divided into sections covering: Income and State Support Receipt; Tenure; Savings and Investments; Disability; Carers; Occupation and Employment; and Pension Participation

Impact of nitrogen flushing and oil choice on the progression of lipid oxidation in unwashed fried sliced potato crisps

Unwashed, sliced, batch-fried potato crisps have a unique texture and are growing in popularity in the UK/EU premium snack food market. In this study, the storage stability of unwashed sliced (high surface starch) potatoes (crisps) fried in regular sunflower oil (SO) or in high oleic sunflower oil (HOSO) was compared over accelerated shelf life testing (45 °C, 6 weeks); with and without nitrogen gas flushing. Primary oxidation products (lipid hydroperoxides) were measured with a ferrous oxidation-xylenol orange (FOX) assay and volatile secondary oxidation products (hexanal) were quantified by using solid phase micro-extraction gas chromatography mass spectrometry (HS-SPME-GC/MS). Results revealed that crisps fried in SO were the least stable. Flushing the stored crisps with nitrogen gas proved to be effective in slowing down the oxidation rate after frying with sunflower oil, significantly stabilizing the crisps. However, crisps fried in HOSO were the most stable, with the lowest rate of development of oxidation markers, and this has previously not been shown for crisps with a high free starch content

Pandemic Paradox: Early Life H2N2 Pandemic Influenza Infection Enhanced Susceptibility to Death during the 2009 H1N1 Pandemic.

Recent outbreaks of H5, H7, and H9 influenza A viruses in humans have served as a vivid reminder of the potentially devastating effects that a novel pandemic could exert on the modern world. Those who have survived infections with influenza viruses in the past have been protected from subsequent antigenically similar pandemics through adaptive immunity. For example, during the 2009 H1N1 "swine flu" pandemic, those exposed to H1N1 viruses that circulated between 1918 and the 1940s were at a decreased risk for mortality as a result of their previous immunity. It is also generally thought that past exposures to antigenically dissimilar strains of influenza virus may also be beneficial due to cross-reactive cellular immunity. However, cohorts born during prior heterosubtypic pandemics have previously experienced elevated risk of death relative to surrounding cohorts of the same population. Indeed, individuals born during the 1890 H3Nx pandemic experienced the highest levels of excess mortality during the 1918 "Spanish flu." Applying Serfling models to monthly mortality and influenza circulation data between October 1997 and July 2014 in the United States and Mexico, we show corresponding peaks in excess mortality during the 2009 H1N1 "swine flu" pandemic and during the resurgent 2013-2014 H1N1 outbreak for those born at the time of the 1957 H2N2 "Asian flu" pandemic. We suggest that the phenomenon observed in 1918 is not unique and points to exposure to pandemic influenza early in life as a risk factor for mortality during subsequent heterosubtypic pandemics.IMPORTANCE The relatively low mortality experienced by older individuals during the 2009 H1N1 influenza virus pandemic has been well documented. However, reported situations in which previous influenza virus exposures have enhanced susceptibility are rare and poorly understood. One such instance occurred in 1918-when those born during the heterosubtypic 1890 H3Nx influenza virus pandemic experienced the highest levels of excess mortality. Here, we demonstrate that this phenomenon was not unique to the 1918 H1N1 pandemic but that it also occurred during the contemporary 2009 H1N1 pandemic and 2013-2014 H1N1-dominated season for those born during the heterosubtypic 1957 H2N2 "Asian flu" pandemic. These data highlight the heretofore underappreciated phenomenon that, in certain instances, prior exposure to pandemic influenza virus strains can enhance susceptibility during subsequent pandemics. These results have important implications for pandemic risk assessment and should inform laboratory studies aimed at uncovering the mechanism responsible for this effect

La culture du vanillier

We use observations of ice sheet surface motion from a Global Positioning System network operating from 2006 to 2014 around North Lake in west Greenland to investigate the dynamical response of the Greenland Ice Sheet's ablation area to interannual variability in surface melting. We find no statistically significant relationship between runoff season characteristics and ice flow velocities within a given year or season. Over the 7 year time series, annual velocities at North Lake decrease at an average rate of −0.9 ± 1.1 m yr−2, consistent with the negative trend in annual velocities observed in neighboring regions over recent decades. We find that net runoff integrated over several preceding years has a negative correlation with annual velocities, similar to findings from the two other available decadal records of ice velocity in western Greenland. However, we argue that this correlation is not necessarily evidence for a direct hydrologic mechanism acting on the timescale of multiple years but could be a statistical construct. Finally, we stress that neither the decadal slowdown trend nor the negative correlation between velocity and integrated runoff is predicted by current ice-sheet models, underscoring that these models do not yet capture all the relevant feedbacks between runoff and ice dynamics needed to predict long-term trends in ice sheet flow

Short-term variability in Greenland Ice Sheet motion forced by time-varying meltwater inputs: implications for the relationship between subglacial drainage system behavior and ice velocity.

High resolution measurements of ice motion along a -120 km transect in a land-terminating section of the GrIS reveal short-term velocity variations (<1 day), which are forced by rapid variations in meltwater input to the subglacial drainage system from the ice sheet surface. The seasonal changes in ice velocity at low elevations (<1000 m) are dominated by events lasting from 1 day to 1 week, although daily cycles are largely absent at higher elevations, reflecting different patterns of meltwater input. Using a simple model of subglacial conduit behavior we show that the seasonal record of ice velocity can be understood in terms of a time-varying water input to a channelized subglacial drainage system. Our investigation substantiates arguments that variability in the duration and rate, rather than absolute volume, of meltwater delivery to the subglacial drainage system are important controls on seasonal patterns of subglacial water pressure, and therefore ice velocity. We suggest that interpretations of hydro-dynamic behavior in land-terminating sections of the GrIS margin which rely on steady state drainage theories are unsuitable for making predictions about the effect of increased summer ablation on future rates of ice motion. © 2012. American Geophysical Union

In Context: Lessons About Adolescent Unipolar Depression From the Improving Mood With Psychoanalytic and Cognitive Therapies Trial

This review paper summarizes the results of the Improving Mood with Psychoanalytic and Cognitive Therapies (IMPACT) study and its implications for psychological treatment of adolescents with moderate to severe unipolar major depression. IMPACT was a pragmatic, superiority, randomized controlled trial conducted in the United Kingdom, which compared the clinical and cost-effectiveness of short-term psychoanalytic therapy (STPP), cognitive−behavioral therapy (CBT), and a brief psychosocial intervention (BPI) in reducing depression symptoms in 465 adolescents with unipolar major depression, aged 11 to 17 years. Although this was a clinically heterogeneous group of adolescents, some symptoms (eg, sleep and concentration difficulties, irritability/anger) were common and disabling. The trial reported no significant difference among the 3 treatments in reducing depression symptoms. One year after treatment, 84% of participants showed improvement in depressive symptoms (<50% of baseline symptoms) and improved psychosocial functioning, achieving this through different symptom reduction trajectories. Although participants attended fewer treatment sessions than planned, the 3 treatments were delivered with fidelity to their respective models. Ending treatment without therapist agreement occurred in 37% of cases. This was not associated with outcomes by treatment group. Adolescents emphasized the importance of the therapeutic relationship in all 3 treatments. Results suggest that although most adolescents respond to time-limited, structured psychological therapy, subgroups of depressed adolescents are likely to need additional treatment or support. These include adolescents who live in complex circumstances and/or who believe that their needs are not met in therapy, some who stop treatment early, and the 16% to 18% of adolescents who do not respond to treatment

Kinome Profiling Identifies Druggable Targets for Novel Human Cytomegalovirus (HCMV) Antivirals

Human cytomegalovirus (HCMV) is a significant cause of disease in immune-compromised adults and immune naïve newborns. No vaccine exists to prevent HCMV infection, and current antiviral therapies have toxic side effects that limit the duration and intensity of their use. There is thus an urgent need for new strategies to treat HCMV infection. Repurposing existing drugs as antivirals is an attractive approach to limit the time and cost of new antiviral drug development. Virus-induced changes in infected cells are often driven by changes in cellular kinase activity, which led us to hypothesize that defining the complement of kinases (the kinome), whose abundance or expression is altered during infection would identify existing kinase inhibitors that could be repurposed as new antivirals. To this end, we applied a kinase capture technique, multiplexed kinase inhibitor bead-mass spectrometry (MIB-MS) kinome, to quantitatively measure perturbations in >240 cellular kinases simultaneously in cells infected with a laboratory-adapted (AD169) or clinical (TB40E) HCMV strain. MIB-MS profiling identified time-dependent increases and decreases in MIB binding of multiple kinases including cell cycle kinases, receptor tyrosine kinases, and mitotic kinases. Based on the kinome data, we tested the antiviral effects of kinase inhibitors and other compounds, several of which are in clinical use or development. Using a novel flow cytometry-based assay and a fluorescent reporter virus we identified three compounds that inhibited HCMV replication with IC 50 values of 3 log decrease in virus replication. These results show the utility of MIB-MS kinome profiling for identifying existing kinase inhibitors that can potentially be repurposed as novel antiviral drugs

In Context: lessons about adolescent unipolar depression from the improving mood with psychoanalytic and cognitive therapies trial

This review paper summarizes the results of the Improving Mood with Psychoanalytic and Cognitive Therapies (IMPACT) study and its implications for psychological treatment of adolescents with moderate to severe unipolar major depression. IMPACT was a pragmatic, superiority, randomized controlled trial conducted in the United Kingdom, which compared the clinical and cost-effectiveness of short-term psychoanalytic therapy (STPP), cognitive−behavioral therapy (CBT), and a brief psychosocial intervention (BPI) in reducing depression symptoms in 465 adolescents with unipolar major depression, aged 11 to 17 years. Although this was a clinically heterogeneous group of adolescents, some symptoms (eg, sleep and concentration difficulties, irritability/anger) were common and disabling. The trial reported no significant difference among the 3 treatments in reducing depression symptoms. One year after treatment, 84% of participants showed improvement in depressive symptoms (<50% of baseline symptoms) and improved psychosocial functioning, achieving this through different symptom reduction trajectories. Although participants attended fewer treatment sessions than planned, the 3 treatments were delivered with fidelity to their respective models. Ending treatment without therapist agreement occurred in 37% of cases. This was not associated with outcomes by treatment group. Adolescents emphasized the importance of the therapeutic relationship in all 3 treatments. Results suggest that although most adolescents respond to time-limited, structured psychological therapy, subgroups of depressed adolescents are likely to need additional treatment or support. These include adolescents who live in complex circumstances and/or who believe that their needs are not met in therapy, some who stop treatment early, and the 16% to 18% of adolescents who do not respond to treatment

Mitochondrial Protease ClpP is a Target for the Anticancer Compounds ONC201 and Related Analogues

ONC201 is a first-in-class imipridone molecule currently in clinical trials for the treatment of multiple cancers. Despite enormous clinical potential, the mechanism of action is controversial. To investigate the mechanism of ONC201 and identify compounds with improved potency, we tested a series of novel ONC201 analogues (TR compounds) for effects on cell viability and stress responses in breast and other cancer models. The TR compounds were found to be ∼50-100 times more potent at inhibiting cell proliferation and inducing the integrated stress response protein ATF4 than ONC201. Using immobilized TR compounds, we identified the human mitochondrial caseinolytic protease P (ClpP) as a specific binding protein by mass spectrometry. Affinity chromatography/drug competition assays showed that the TR compounds bound ClpP with ∼10-fold higher affinity compared to ONC201. Importantly, we found that the peptidase activity of recombinant ClpP was strongly activated by ONC201 and the TR compounds in a dose- and time-dependent manner with the TR compounds displaying a ∼10-100 fold increase in potency over ONC201. Finally, siRNA knockdown of ClpP in SUM159 cells reduced the response to ONC201 and the TR compounds, including induction of CHOP, loss of the mitochondrial proteins (TFAM, TUFM), and the cytostatic effects of these compounds. Thus, we report that ClpP directly binds ONC201 and the related TR compounds and is an important biological target for this class of molecules. Moreover, these studies provide, for the first time, a biochemical basis for the difference in efficacy between ONC201 and the TR compounds