Coherent rotations of a single spin-based qubit in a single quantum dot at fixed Zeeman energy

Coherent rotations of single spin-based qubits may be accomplished electrically at fixed Zeeman energy with a qubit defined solely within a single electrostatically-defined quantum dot; the $g$-factor and the external magnetic field are kept constant. All that is required to be varied are the voltages on metallic gates which effectively change the shape of the elliptic quantum dot. The pseudospin-1/2 qubit is constructed from the two-dimensional $S=1/2$, $S_z=-1/2$ subspace of three interacting electrons in a two-dimensional potential well. Rotations are created by altering the direction of the pseudomagnetic field through changes in the shape of the confinement potential. By deriving an exact analytic solution to the long-range Coulomb interaction matrix elements, we calculate explicitly the range of magnitudes and directions the pseudomagnetic field can take. Numerical estimates are given for {GaAs}.Comment: Restructured manuscript, more details shown (results unchanged); Six pages, revtex4; More info at http://soliton.phys.dal.c

Post-mortem diagnosis of kidney impairment:an experimental study

The determination of the role that drugs may have played in a death is an important part of the investigation into unexplained deaths. Renal impairment may lead to a reduction in drug excretion rate and therefore an accumulation of drugs or metabolites, leading to possible toxic or lethal effects. Creatinine levels are known to be stable in the post mortem period and in life can give an indication of kidney function. There are however widely reported limitations when using creatinine in isolation and so we investigated the usefulness of using estimated glomerular filtration rate (eGFR) for scoring an individual as having renal impairment using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula. We analysed unpreserved vitreous for creatinine in 812 individuals using an isotope dilution mass spectrometry (ID-MS) traceable enzymatic. We found that the biochemical analysis of post mortem vitreous creatinine and subsequent calculation of eGFR is a useful adjunct to the standard testing that takes place during a post-mortem examination and can assist in death investigation. Using an eGFR of <60 mL/min/1.73 m2 gave a sensitivity of 94.3% and specificity of 97.3% when scoring an individual as having renal impairment. We therefore recommend the calculation of eGFR for the determination of possible renal impairment in post mortem investigations. It is, of course, always pertinent to interpret any results using a wealth of case information. Extreme caution should be exercised in cases where insufficient clinical information/history is available, particularly in cases in which there is suspected diabetic ketoacidosis, dehydration or hospitalisation prior to death

High burden of Schistosoma mansoni infection in school-aged children in Marolambo District, Madagascar.

BACKGROUND: A school-based survey was undertaken to assess prevalence and infection intensity of schistosomiasis in school-aged children in the Marolambo District of Madagascar. METHODS: School-aged children from six purposively selected schools were tested for Schistosoma haematobium by urine filtration and Schistosoma mansoni using circulating cathodic antigen (CCA) and Kato-Katz stool analysis. The investigators did not address soil-transmitted helminths (STH) in this study. RESULTS: Of 399 school-aged children screened, 93.7% were infected with S. mansoni based on CCA analysis. Kato-Katz analysis of stool revealed S. mansoni infection in 73.6% (215/ 292). Heavy infections (> 400 eggs per gram) were common (32.1%; 69/ 215), with a mean of 482 eggs per gram of stool. Moderate infection intensities were detected in 31.2% (67/ 215) and light infection intensities in 36.7% (79/ 215) of infected participants. No infection with S. haematobium was detected by urine filtration. CONCLUSIONS: Intestinal schistosomiasis appears a considerable public health issue in this remote area of Madagascar where there is a pressing need for mass drug administration

HDAC1 modulates OGG1-initiated oxidative DNA damage repair in the aging brain and Alzheimer’s disease

DNA damage contributes to brain aging and neurodegenerative diseases. However, the factors stimulating DNA repair to stave off functional decline remain obscure. We show that HDAC1 modulates OGG1-initated 8-oxoguanine (8-oxoG) repair in the brain. HDAC1-deficient mice display age-associated DNA damage accumulation and cognitive impairment. HDAC1 stimulates OGG1, a DNA glycosylase known to remove 8-oxoG lesions that are associated with transcriptional repression. HDAC1 deficiency causes impaired OGG1 activity, 8-oxoG accumulation at the promoters of genes critical for brain function, and transcriptional repression. Moreover, we observe elevated 8-oxoG along with reduced HDAC1 activity and downregulation of a similar gene set in the 5XFAD mouse model of Alzheimer’s disease. Notably, pharmacological activation of HDAC1 alleviates the deleterious effects of 8-oxoG in aged wild-type and 5XFAD mice. Our work uncovers important roles for HDAC1 in 8-oxoG repair and highlights the therapeutic potential of HDAC1 activation to counter functional decline in brain aging and neurodegeneration

HDAC1 modulates OGG1-initiated oxidative DNA damage repair in the aging brain and Alzheimer’s disease

DNA damage contributes to brain aging and neurodegenerative diseases. However, the factors stimulating DNA repair to stave off functional decline remain obscure. We show that HDAC1 modulates OGG1-initated 8-oxoguanine (8-oxoG) repair in the brain. HDAC1-deficient mice display age-associated DNA damage accumulation and cognitive impairment. HDAC1 stimulates OGG1, a DNA glycosylase known to remove 8-oxoG lesions that are associated with transcriptional repression. HDAC1 deficiency causes impaired OGG1 activity, 8-oxoG accumulation at the promoters of genes critical for brain function, and transcriptional repression. Moreover, we observe elevated 8-oxoG along with reduced HDAC1 activity and downregulation of a similar gene set in the 5XFAD mouse model of Alzheimer’s disease. Notably, pharmacological activation of HDAC1 alleviates the deleterious effects of 8-oxoG in aged wild-type and 5XFAD mice. Our work uncovers important roles for HDAC1 in 8-oxoG repair and highlights the therapeutic potential of HDAC1 activation to counter functional decline in brain aging and neurodegeneration

Analysis of the 10q11 Cancer Risk Locus Implicates MSMB and NCOA4 in Human Prostate Tumorigenesis

Genome-wide association studies (GWAS) have established a variant, rs10993994, on chromosome 10q11 as being associated with prostate cancer risk. Since the variant is located outside of a protein-coding region, the target genes driving tumorigenesis are not readily apparent. Two genes nearest to this variant, MSMB and NCOA4, are strong candidates for mediating the effects of rs109939934. In a cohort of 180 individuals, we demonstrate that the rs10993994 risk allele is associated with decreased expression of two MSMB isoforms in histologically normal and malignant prostate tissue. In addition, the risk allele is associated with increased expression of five NCOA4 isoforms in histologically normal prostate tissue only. No consistent association with either gene is observed in breast or colon tissue. In conjunction with these findings, suppression of MSMB expression or NCOA4 overexpression promotes anchorage-independent growth of prostate epithelial cells, but not growth of breast epithelial cells. These data suggest that germline variation at chromosome 10q11 contributes to prostate cancer risk by influencing expression of at least two genes. More broadly, the findings demonstrate that disease risk alleles may influence multiple genes, and associations between genotype and expression may only be observed in the context of specific tissue and disease states

Anticipatory changes in British household purchases of soft drinks associated with the announcement of the Soft Drinks Industry Levy: A controlled interrupted time series analysis

Background: Sugar-sweetened beverage (SSB) consumption is positively associated with obesity, type 2 diabetes, and cardiovascular disease. The World Health Organization recommends that member states implement effective taxes on SSBs to reduce consumption. The United Kingdom Soft Drinks Industry Levy (SDIL) is a two-tiered tax, announced in March 2016 and implemented in April 2018. Drinks with ≥8 g of sugar per 100 ml (higher levy tier) are taxed at £0.24 per litre, drinks with ≥5 to 1.2% alcohol by volume are exempt. We aimed to determine if the announcement of the SDIL was associated with anticipatory changes in purchases of soft drinks prior to implementation of the SDIL in April 2018. We explored differences in the volume of and amount of sugar in household purchases of drinks in each levy tier at 2 years post announcement. Methods and findings: We used controlled interrupted time series to compare observed changes associated with the announcement of the SDIL to the counterfactual scenario of no announcement. We used data from Kantar Worldpanel, a commercial household purchasing panel with approximately 30,000 British members that includes linked nutritional data on purchases. We conducted separate analyses for drinks liable for the SDIL in the higher, lower, and no-levy tiers controlling with household purchase volumes of toiletries. At 2 years post announcement, there was no difference in volume of or sugar from purchases of higher-levy-tier drinks compared to the counterfactual of no announcement. In contrast, a reversal of the existing upward trend in volume (ml) of and amount of sugar (g) in purchases of lower-levy-tier drinks was seen. These changes led to a −96.1 ml (95% confidence interval [CI] −144.2 to −48.0) reduction in volume and −6.4 g (95% CI −9.8 to −3.1) reduction in sugar purchased in these drinks per household per week. There was a reversal of the existing downward trend in the amount of sugar in household purchases of the no-levy drinks but no change in volume purchased. At 2 years post announcement, these changes led to a 6.1 g (95% CI 3.9–8.2) increase in sugar purchased in these drinks per household per week. There was no evidence that volume of or amount of sugar in purchases of all drinks combined was different from the counterfactual. This is an observational study, and changes other than the SDIL may have been responsible for the results reported. Purchases consumed outside of the home were not accounted for. Conclusions: The announcement of the UK SDIL was associated with reductions in volume and sugar purchased in lower-levy-tier drinks before implementation. These were offset by increases in sugar purchased from no-levy drinks. These findings may reflect reformulation of drinks from the lower levy to no-levy tier with removal of some but not all sugar, alongside changes in consumer attitudes and beliefs. Trial registration: ISRCTN Registry ISRCTN18042742

Anticipatory changes in British household purchases of soft drinks associated with the announcement of the Soft Drinks Industry Levy: A controlled interrupted time series analysis

Background: Sugar-sweetened beverage (SSB) consumption is positively associated with obesity, type 2 diabetes, and cardiovascular disease. The World Health Organization recommends that member states implement effective taxes on SSBs to reduce consumption. The United Kingdom Soft Drinks Industry Levy (SDIL) is a two-tiered tax, announced in March 2016 and implemented in April 2018. Drinks with ≥8 g of sugar per 100 ml (higher levy tier) are taxed at £0.24 per litre, drinks with ≥5 to 1.2% alcohol by volume are exempt. We aimed to determine if the announcement of the SDIL was associated with anticipatory changes in purchases of soft drinks prior to implementation of the SDIL in April 2018. We explored differences in the volume of and amount of sugar in household purchases of drinks in each levy tier at 2 years post announcement. Methods and findings: We used controlled interrupted time series to compare observed changes associated with the announcement of the SDIL to the counterfactual scenario of no announcement. We used data from Kantar Worldpanel, a commercial household purchasing panel with approximately 30,000 British members that includes linked nutritional data on purchases. We conducted separate analyses for drinks liable for the SDIL in the higher, lower, and no-levy tiers controlling with household purchase volumes of toiletries. At 2 years post announcement, there was no difference in volume of or sugar from purchases of higher-levy-tier drinks compared to the counterfactual of no announcement. In contrast, a reversal of the existing upward trend in volume (ml) of and amount of sugar (g) in purchases of lower-levy-tier drinks was seen. These changes led to a −96.1 ml (95% confidence interval [CI] −144.2 to −48.0) reduction in volume and −6.4 g (95% CI −9.8 to −3.1) reduction in sugar purchased in these drinks per household per week. There was a reversal of the existing downward trend in the amount of sugar in household purchases of the no-levy drinks but no change in volume purchased. At 2 years post announcement, these changes led to a 6.1 g (95% CI 3.9–8.2) increase in sugar purchased in these drinks per household per week. There was no evidence that volume of or amount of sugar in purchases of all drinks combined was different from the counterfactual. This is an observational study, and changes other than the SDIL may have been responsible for the results reported. Purchases consumed outside of the home were not accounted for. Conclusions: The announcement of the UK SDIL was associated with reductions in volume and sugar purchased in lower-levy-tier drinks before implementation. These were offset by increases in sugar purchased from no-levy drinks. These findings may reflect reformulation of drinks from the lower levy to no-levy tier with removal of some but not all sugar, alongside changes in consumer attitudes and beliefs. Trial registration: ISRCTN Registry ISRCTN18042742

Changes in soft drinks purchased by British households associated with the UK soft drinks industry levy: controlled interrupted time series analysis

Abstract: Objective: To determine changes in household purchases of drinks and confectionery one year after implementation of the UK soft drinks industry levy (SDIL). Design: Controlled interrupted time series analysis. Participants: Members of a panel of households reporting their purchasing on a weekly basis to a market research company (average weekly number of participants n=22 183), March 2014 to March 2019. Intervention: A two tiered tax levied on manufacturers of soft drinks, announced in March 2016 and implemented in April 2018. Drinks with ≥8 g sugar/100 mL (high tier) are taxed at £0.24/L and drinks with ≥5 to <8 g sugar/100 mL (low tier) are taxed at £0.18/L. Drinks with <5 g sugar/100 mL (no levy) are not taxed. Main outcome measures: Absolute and relative differences in the volume of, and amount of sugar in, soft drinks categories, all soft drinks combined, alcohol, and confectionery purchased per household per week one year after implementation of the SDIL compared with trends before the announcement of the SDIL. Results: In March 2019, compared with the counterfactual estimated from pre-announcement trends, purchased volume of drinks in the high levy tier decreased by 155 mL (95% confidence interval 240.5 to 69.5 mL) per household per week, equivalent to 44.3% (95% confidence interval 59.9% to 28.7%), and sugar purchased in these drinks decreased by 18.0 g (95% confidence interval 32.3 to 3.6 g), or 45.9% (68.8% to 22.9%). Purchases of low tier drinks decreased by 177.3 mL (225.3 to 129.3 mL) per household per week, or 85.9% (95.1% to 76.7%), with a 12.5 g (15.4 to 9.5 g) reduction in sugar in these drinks, equivalent to 86.2% (94.2% to 78.1%). Despite no overall change in volume of no levy drinks purchased, there was an increase in sugar purchased of 15.3 g (12.6 to 17.9 g) per household per week, equivalent to 166.4% (94.2% to 238.5%). When all soft drinks were combined, the volume of drinks purchased did not change, but sugar decreased by 29.5 g (55.8 to 3.1 g), or 9.8% (17.9% to 1.8%). Purchases of confectionery and alcoholic drinks did not change. Conclusions: Compared with trends before the SDIL was announced, one year after implementation, the volume of soft drinks purchased did not change. The amount of sugar in those drinks was 30 g, or 10%, lower per household per week—equivalent to one 250 mL serving of a low tier drink per person per week. The SDIL might benefit public health without harming industry. Trial registration: ISRCTN18042742