Public Health England's sugar reduction programme did not "fail"

Measuring what food people buy is difficult, analysing the data arduous. Public Health England honestly acknowledged, up front, that the figures on sugar reductions in foods were based on purchasing surveys conducted in August-September 2017, 8-9 months before the report was published. Reformulation takes time. Even with soft drinks, where sugar reduction is easiest, many companies only completed work just before the levy came into force. Reformulating foods is technically more difficult. Further, as mentioned in our recent article for BMJ Opinion,2 the UK’s complex distribution system means that many products, successfully reformulated, are not yet in shops. They certainly were not available for purchase in August and September last year. If we could have measured the extent of sugar reduction up-to-the-minute, in May 2018, the figure for foods would certainly have been much larger than 2%, for drinks much larger than 11%. In the real world, today, the sugar reduction programme is probably a success. But The BMJ’s story carries a warning for Public Health England. Unless it changes or supplements its data sources, unless it shortens or changes its data analysis, then its next report, early in 2019, will generate more stories about slow progress. Public Health England will again be accused of failing. And that would be in no one’s interest, least of all Public Health England’s

Weak localization in mesoscopic hole transport: Berry phases and classical correlations

We consider phase-coherent transport through ballistic and diffusive two-dimensional hole systems based on the Kohn-Luttinger Hamiltonian. We show that intrinsic heavy-hole light-hole coupling gives rise to clear-cut signatures of an associated Berry phase in the weak localization which renders the magneto-conductance profile distinctly different from electron transport. Non-universal classical correlations determine the strength of these Berry phase effects and the effective symmetry class, leading even to antilocalization-type features for circular quantum dots and Aharonov-Bohm rings in the absence of additional spin-orbit interaction. Our semiclassical predictions are quantitatively confirmed by numerical transport calculations

Genetic basis of neurocognitive decline and reduced white-matter integrity in normal human brain aging

Identification of genes associated with brain aging should markedly improve our understanding of the biological processes that govern normal age-related decline. However, challenges to identifying genes that facilitate successful brain aging are considerable, including a lack of established phenotypes and difficulties in modeling the effects of aging per se, rather than genes that influence the underlying trait. In a large cohort of randomly selected pedigrees (n = 1,129 subjects), we documented profound aging effects from young adulthood to old age (18-83 y) on neurocognitive ability and diffusion-based white-matter measures. Despite significant phenotypic correlation between white-matter integrity and tests of processing speed, working memory, declarative memory, and intelligence, no evidence for pleiotropy between these classes of phenotypes was observed. Applying an advanced quantitative gene-by-environment interaction analysis where age is treated as an environmental factor, we demonstrate a heritable basis for neurocognitive deterioration as a function of age. Furthermore, by decomposing gene-by-aging (G × A) interactions, we infer that different genes influence some neurocognitive traits as a function of age, whereas other neurocognitive traits are influenced by the same genes, but to differential levels, from young adulthood to old age. In contrast, increasing white-matter incoherence with age appears to be nongenetic. These results clearly demonstrate that traits sensitive to the genetic influences on brain aging can be identified, a critical first step in delineating the biological mechanisms of successful aging

Pennsylvania Folklife Vol. 25, No. 1

• Pennsylvania German Tombstone Art of Lebanon County, Pennsylvania • Rain Day in Waynesburg, Pennsylvania • Non-Ordinary Stoneware Pieces from New Geneva and Greensboro, Pennsylvania • Pennsylvania German Astronomy and Astrology XIII: Conjunctions of 1683, 1694, and 1743 • The Social Context of Musical Instruments within the Pennsylvania German Culture • Tourism and the Amish Way of Life • Home Brewing Techniques: Folk-Cultural Questionnaire No. 41https://digitalcommons.ursinus.edu/pafolklifemag/1065/thumbnail.jp

Pennsylvania Folklife Vol. 22, No. 4

• Let\u27s Talk About Slate • Ephrata Cloister Wills • A Blacksmith\u27s Summerkich • Pennsylvania German Astronomy and Astrology VI: Astrological Philosophy • Stoneware from New Geneva and Greensboro, Pennsylvania • American Emigration Materials from Pfeddersheim • Folk Medicine - Home Remedies: Folk-Cultural Questionnaire No. 29https://digitalcommons.ursinus.edu/pafolklifemag/1053/thumbnail.jp

High dimensional endophenotype ranking in the search for major depression risk genes.

BACKGROUND: Despite overwhelming evidence that major depression is highly heritable, recent studies have localized only a single depression-related locus reaching genome-wide significance and have yet to identify a causal gene. Focusing on family-based studies of quantitative intermediate phenotypes or endophenotypes, in tandem with studies of unrelated individuals using categorical diagnoses, should improve the likelihood of identifying major depression genes. However, there is currently no empirically derived statistically rigorous method for selecting optimal endophentypes for mental illnesses. Here, we describe the endophenotype ranking value, a new objective index of the genetic utility of endophenotypes for any heritable illness. METHODS: Applying endophenotype ranking value analysis to a high-dimensional set of over 11,000 traits drawn from behavioral/neurocognitive, neuroanatomic, and transcriptomic phenotypic domains, we identified a set of objective endophenotypes for recurrent major depression in a sample of Mexican American individuals (n = 1122) from large randomly selected extended pedigrees. RESULTS: Top-ranked endophenotypes included the Beck Depression Inventory, bilateral ventral diencephalon volume, and expression levels of the RNF123 transcript. To illustrate the utility of endophentypes in this context, each of these traits were utlized along with disease status in bivariate linkage analysis. A genome-wide significant quantitative trait locus was localized on chromsome 4p15 (logarithm of odds = 3.5) exhibiting pleiotropic effects on both the endophenotype (lymphocyte-derived expression levels of the RNF123 gene) and disease risk. CONCLUSIONS: The wider use of quantitative endophenotypes, combined with unbiased methods for selecting among these measures, should spur new insights into the biological mechanisms that influence mental illnesses like major depression

Hypocapnia is a biological marker for orthostatic intolerance in some patients with chronic fatigue syndrome

CONTEXT: Patients with chronic fatigue syndrome and those with orthostatic intolerance share many symptoms, yet questions exist as to whether CFS patients have physiological evidence of orthostatic intolerance. OBJECTIVE: To determine if some CFS patients have increased rates of orthostatic hypotension, hypertension, tachycardia, or hypocapnia relative to age-matched controls. DESIGN: Assess blood pressure, heart rate, respiratory rate, end tidal CO2 and visual analog scales for orthostatic symptoms when supine and when standing for 8 minutes without moving legs. SETTING: Referral practice and research center. PARTICIPANTS: 60 women and 15 men with CFS and 36 women and 4 men serving as age matched controls with analyses confined to 62 patients and 35 controls showing either normal orthostatic testing or a physiological abnormal test. MAIN OUTCOME MEASURES: Orthostatic tachycardia; orthostatic hypotension; orthostatic hypertension; orthostatic hypocapnia or combinations thereof. RESULTS: CFS patients had higher rates of abnormal tests than controls (53% vs 20%, p < .002), but rates of orthostatic tachycardia, orthostatic hypotension, and orthostatic hypertension did not differ significantly between patients and controls (11.3% vs 5.7%, 6.5% vs 2.9%, 19.4% vs 11.4%, respectively). In contrast, rates of orthostatic hypocapnia were significantly higher in CFS than in controls (20.6% vs 2.9%, p < .02). This CFS group reported significantly more feelings of illness and shortness of breath than either controls or CFS patients with normal physiological tests. CONCLUSION: A substantial number of CFS patients have orthostatic intolerance in the form of orthostatic hypocapnia. This allows subgrouping of patients with CFS and thus reduces patient pool heterogeneity engendered by use of a clinical case definition

Modulation of the stability of the Salmonella fourU-type RNA thermometer

RNA thermometers are translational control elements that regulate the expression of bacterial heat shock and virulence genes. They fold into complex secondary structures that block translation at low temperatures. A temperature increase releases the ribosome binding site and thus permits translation initiation. In fourU-type RNA thermometers, the AGGA sequence of the SD region is paired with four consecutive uridines. We investigated the melting points of the wild-type and mutant sequences. It was decreased by 5°C when a stabilizing GC basepair was exchanged by an AU pair or increased by 11°C when an internal AG mismatch was converted to a GC pair, respectively. Stabilized or destabilized RNA structures are directly correlated with decreased or increased in vivo gene expression, respectively. Mg2+ also affected the melting point of the fourU thermometer. Variations of the Mg2+ concentration in the physiological range between 1 and 2 mM translated into a 2.8°C shift of the melting point. Thus, Mg2+ binding to the hairpin RNA is regulatory relevant. Applying three different NMR techniques, two Mg2+ binding sites were found in the hairpin structure. One of these binding sites could be identified as outer sphere binding site that is located within the fourU motif. Binding of the two Mg2+ ions exhibits a positive cooperativity with a Hill coefficient of 1.47. Free energy values ΔG for Mg2+ binding determined by NMR are in agreement with data determined from CD measurements

Modulation of the stability of the Salmonella fourU-type RNA thermometer

RNA thermometers are translational control elements that regulate the expression of bacterial heat shock and virulence genes. They fold into complex secondary structures that block translation at low temperatures. A temperature increase releases the ribosome binding site and thus permits translation initiation. In fourU-type RNA thermometers, the AGGA sequence of the SD region is paired with four consecutive uridines. We investigated the melting points of the wild-type and mutant sequences. It was decreased by 5°C when a stabilizing GC basepair was exchanged by an AU pair or increased by 11°C when an internal AG mismatch was converted to a GC pair, respectively. Stabilized or destabilized RNA structures are directly correlated with decreased or increased in vivo gene expression, respectively. Mg2+ also affected the melting point of the fourU thermometer. Variations of the Mg2+ concentration in the physiological range between 1 and 2 mM translated into a 2.8°C shift of the melting point. Thus, Mg2+ binding to the hairpin RNA is regulatory relevant. Applying three different NMR techniques, two Mg2+ binding sites were found in the hairpin structure. One of these binding sites could be identified as outer sphere binding site that is located within the fourU motif. Binding of the two Mg2+ ions exhibits a positive cooperativity with a Hill coefficient of 1.47. Free energy values ΔG for Mg2+ binding determined by NMR are in agreement with data determined from CD measurements