Achieving quantum supremacy with sparse and noisy commuting quantum computations

The class of commuting quantum circuits known as IQP (instantaneous quantum polynomial-time) has been shown to be hard to simulate classically, assuming certain complexity-theoretic conjectures. Here we study the power of IQP circuits in the presence of physically motivated constraints. First, we show that there is a family of sparse IQP circuits that can be implemented on a square lattice of n qubits in depth O(sqrt(n) log n), and which is likely hard to simulate classically. Next, we show that, if an arbitrarily small constant amount of noise is applied to each qubit at the end of any IQP circuit whose output probability distribution is sufficiently anticoncentrated, there is a polynomial-time classical algorithm that simulates sampling from the resulting distribution, up to constant accuracy in total variation distance. However, we show that purely classical error-correction techniques can be used to design IQP circuits which remain hard to simulate classically, even in the presence of arbitrary amounts of noise of this form. These results demonstrate the challenges faced by experiments designed to demonstrate quantum supremacy over classical computation, and how these challenges can be overcome.Comment: 23 pages, 1 figure; v4: uses standard journal styl

Replication of LDL SWAs hits in PROSPER/PHASE as validation for future (pharmaco)genetic analyses

<p><b>Background:</b> The PHArmacogenetic study of Statins in the Elderly at risk (PHASE) is a genome wide association study in the PROspective Study of Pravastatin in the Elderly at risk for vascular disease (PROSPER) that investigates the genetic variation responsible for the individual variation in drug response to pravastatin. Statins lower LDL-cholesterol in general by 30%, however not in all subjects. Moreover, clinical response is highly variable and adverse effects occur in a minority of patients. In this report we first describe the rationale of the PROSPER/PHASE project and second show that the PROSPER/PHASE study can be used to study pharmacogenetics in the elderly.</p> <p><b>Methods:</b> The genome wide association study (GWAS) was conducted using the Illumina 660K-Quad beadchips following manufacturer's instructions. After a stringent quality control 557,192 SNPs in 5,244 subjects were available for analysis. To maximize the availability of genetic data and coverage of the genome, imputation up to 2.5 million autosomal CEPH HapMap SNPs was performed with MACH imputation software. The GWAS for LDL-cholesterol is assessed with an additive linear regression model in PROBABEL software, adjusted for age, sex, and country of origin to account for population stratification.</p> <p><b>Results:</b> Forty-two SNPs reached the GWAS significant threshold of p = 5.0e-08 in 5 genomic loci (APOE/APOC1; LDLR; FADS2/FEN1; HMGCR; PSRC1/CELSR5). The top SNP (rs445925, chromosome 19) with a p-value of p = 2.8e-30 is located within the APOC1 gene and near the APOE gene. The second top SNP (rs6511720, chromosome 19) with a p-value of p = 5.22e-15 is located within the LDLR gene. All 5 genomic loci were previously associated with LDL-cholesterol levels, no novel loci were identified. Replication in WOSCOPS and CARE confirmed our results.</p> <p><b>Conclusion:</b> With the GWAS in the PROSPER/PHASE study we confirm the previously found genetic associations with LDL-cholesterol levels. With this proof-of-principle study we show that the PROSPER/PHASE study can be used to investigate genetic associations in a similar way to population based studies. The next step of the PROSPER/PHASE study is to identify the genetic variation responsible for the variation in LDL-cholesterol lowering in response to statin treatment in collaboration with other large trials.</p&gt

Second best toll and capacity optimisation in network: solution algorithm and policy implications

This paper looks at the first and second-best jointly optimal toll and road capacity investment problems from both policy and technical oriented perspectives. On the technical side, the paper investigates the applicability of the constraint cutting algorithm for solving the second-best problem under elastic demand which is formulated as a bilevel programming problem. The approach is shown to perform well despite several problems encountered by our previous work in Shepherd and Sumalee (2004). The paper then applies the algorithm to a small sized network to investigate the policy implications of the first and second-best cases. This policy analysis demonstrates that the joint first best structure is to invest in the most direct routes while reducing capacities elsewhere. Whilst unrealistic this acts as a useful benchmark. The results also show that certain second best policies can achieve a high proportion of the first best benefits while in general generating a revenue surplus. We also show that unless costs of capacity are known to be low then second best tolls will be affected and so should be analysed in conjunction with investments in the network

Assimilation of sea ice thickness derived from CryoSat-2 along-track freeboard measurements into the Met Office's Forecast Ocean Assimilation Model (FOAM)

The feasibility of assimilating sea ice thickness (SIT) observations derived from CryoSat-2 along-track measurements of sea ice freeboard is successfully demonstrated using a 3D-Var assimilation scheme, NEMOVAR, within the Met Office's global, coupled ocean–sea-ice model, Forecast Ocean Assimilation Model (FOAM). The CryoSat-2 Arctic freeboard measurements are produced by the Centre for Polar Observation and Modelling (CPOM) and are converted to SIT within FOAM using modelled snow depth. This is the first time along-track observations of SIT have been used in this way, with other centres assimilating gridded and temporally averaged observations. The assimilation leads to improvements in the SIT analysis and forecast fields generated by FOAM, particularly in the Canadian Arctic. Arctic-wide observation-minus-background assimilation statistics for 2015–2017 show improvements of 0.75 m mean difference and 0.41 m root-mean-square difference (RMSD) in the freeze-up period and 0.46 m mean difference and 0.33 m RMSD in the ice break-up period. Validation of the SIT analysis against independent springtime in situ SIT observations from NASA Operation IceBridge (OIB) shows improvement in the SIT analysis of 0.61 m mean difference (0.42 m RMSD) compared to a control without SIT assimilation. Similar improvements are seen in the FOAM 5 d SIT forecast. Validation of the SIT assimilation with independent Beaufort Gyre Exploration Project (BGEP) sea ice draft observations does not show an improvement, since the assimilated CryoSat-2 observations compare similarly to the model without assimilation in this region. Comparison with airborne electromagnetic induction (Air-EM) combined measurements of SIT and snow depth shows poorer results for the assimilation compared to the control, despite covering similar locations to the OIB and BGEP datasets. This may be evidence of sampling uncertainty in the matchups with the Air-EM validation dataset, owing to the limited number of observations available over the time period of interest. This may also be evidence of noise in the SIT analysis or uncertainties in the modelled snow depth, in the assimilated SIT observations, or in the data used for validation. The SIT analysis could be improved by upgrading the observation uncertainties used in the assimilation. Despite the lack of CryoSat-2 SIT observations available for assimilation over the summer due to the detrimental effect of melt ponds on retrievals, it is shown that the model is able to retain improvements to the SIT field throughout the summer months due to prior, wintertime SIT assimilation. This also results in regional improvements to the July modelled sea ice concentration (SIC) of 5 % RMSD in the European sector, due to slower melt of the thicker sea ice

Mid-Upper Arm Circumference based Nutrition Programming: evidence for a new approach in regions with high burden of Acute Malnutrition

In therapeutic feeding programs (TFP), mid-upper arm circumference (MUAC) shows advantages over weight-for-height Z score (WHZ) and is recommended by the World Health Organization (WHO) as an independent criterion for screening children 6-59 months old. Here we report outcomes and treatment response from a TFP using MUAC ≤118 mm or oedema as sole admission criteria for severe acute malnutrition (SAM)

Increasing the frequency of hand washing by healthcare workers does not lead to commensurate reductions in staphylococcal infection in a hospital ward

Hand hygiene is generally considered to be the most important measure that can be applied to prevent the spread of healthcare-associated infection (HAI). Continuous emphasis on this intervention has lead to the widespread opinion that HAI rates can be greatly reduced by increased hand hygiene compliance alone. However, this assumes that the effectiveness of hand hygiene is not constrained by other factors and that improved compliance in excess of a given level, in itself, will result in a commensurate reduction in the incidence of HAI. However, several researchers have found the law of diminishing returns to apply to hand hygiene, with the greatest benefits occurring in the first 20% or so of compliance, and others have demonstrated that poor cohorting of nursing staff profoundly influences the effectiveness of hand hygiene measures. Collectively, these findings raise intriguing questions about the extent to which increasing compliance alone can further reduce rates of HAI. In order to investigate these issues further, we constructed a deterministic Ross-Macdonald model and applied it to a hypothetical general medical ward. In this model the transmission of staphylococcal infection was assumed to occur after contact with the transiently colonized hands of HCWs, who, in turn, acquire contamination only by touching colonized patients. The aim of the study was to evaluate the impact of imperfect hand cleansing on the transmission of staphylococcal infection and to identify, whether there is a limit, above which further hand hygiene compliance is unlikely to be of benefit. The model demonstrated that if transmission is solely via the hands of HCWs, it should, under most circumstances, be possible to prevent outbreaks of staphylococcal infection from occurring at a hand cleansing frequencies <50%, even with imperfect hand hygiene. The analysis also indicated that the relationship between hand cleansing efficacy and frequency is not linear - as efficacy decreases, so the hand cleansing frequency required to ensure R0<1 increases disproportionately. Although our study confirmed hand hygiene to be an effective control measure, it demonstrated that the law of diminishing returns applies, with the greatest benefit derived from the first 20% or so of compliance. Indeed, our analysis suggests that there is little benefit to be accrued from very high levels of hand cleansing and that in most situations compliance >40% should be enough to prevent outbreaks of staphylococcal infection occurring, if transmission is solely via the hands of HCWs. Furthermore we identified a non-linear relationship between hand cleansing efficacy and frequency, suggesting that it is important to maximise the efficacy of the hand cleansing process

Projections of the current and future disease burden of hepatitis C virus infection in Malaysia

The prevalence of hepatitis C virus (HCV) infection in Malaysia has been estimated at 2.5% of the adult population. Our objective, satisfying one of the directives of the WHO Framework for Global Action on Viral Hepatitis, was to forecast the HCV disease burden in Malaysia using modelling methods.An age-structured multi-state Markov model was developed to simulate the natural history of HCV infection. We tested three historical incidence scenarios that would give rise to the estimated prevalence in 2009, and calculated the incidence of cirrhosis, end-stage liver disease, and death, and disability-adjusted life-years (DALYs) under each scenario, to the year 2039. In the baseline scenario, current antiviral treatment levels were extended from 2014 to the end of the simulation period. To estimate the disease burden averted under current sustained virological response rates and treatment levels, the baseline scenario was compared to a counterfactual scenario in which no past or future treatment is assumed.In the baseline scenario, the projected disease burden for the year 2039 is 94,900 DALYs/year (95% credible interval (CrI): 77,100 to 124,500), with 2,002 (95% CrI: 1340 to 3040) and 540 (95% CrI: 251 to 1,030) individuals predicted to develop decompensated cirrhosis and hepatocellular carcinoma, respectively, in that year. Although current treatment practice is estimated to avert a cumulative total of 2,200 deaths from DC or HCC, a cumulative total of 63,900 HCV-related deaths is projected by 2039.The HCV-related disease burden is already high and is forecast to rise steeply over the coming decades under current levels of antiviral treatment. Increased governmental resources to improve HCV screening and treatment rates and to reduce transmission are essential to address the high projected HCV disease burden in Malaysia

MEF2A regulates mGluR-dependent AMPA receptor trafficking independently of Arc/Arg3.1

© 2018 The Author(s). Differential trafficking of AMPA receptors (AMPARs) to and from the postsynaptic membrane is a key determinant of the strength of excitatory neurotransmission, and is thought to underlie learning and memory. The transcription factor MEF2 is a negative regulator of memory in vivo, in part by regulating trafficking of the AMPAR subunit GluA2, but the molecular mechanisms behind this have not been established. Here we show, via knockdown of endogenous MEF2A in primary neuronal culture, that MEF2A is specifically required for Group I metabotropic glutamate receptor (mGluR)-mediated GluA2 internalisation, but does not regulate AMPAR expression or trafficking under basal conditions. Furthermore, this process occurs independently of changes in expression of Arc/Arg3.1, a previously characterised MEF2 transcriptional target and mediator of mGluR-dependent long-term depression. These data demonstrate a novel MEF2A-dependent mechanism for the regulation of activity-dependent AMPAR trafficking

Divergence exists in the subcellular distribution of intramuscular triglyceride in human skeletal muscle dependent on the choice of lipid dye.

Despite over 50 years of research, a comprehensive understanding of how intramuscular triglyceride (IMTG) is stored in skeletal muscle and its contribution as a fuel during exercise is lacking. Immunohistochemical techniques provide information on IMTG content and lipid droplet (LD) morphology on a fibre type and subcellular-specific basis, and the lipid dye Oil Red O (ORO) is commonly used to achieve this. BODIPY 493/503 (BODIPY) is an alternative lipid dye with lower background staining and narrower emission spectra. Here we provide the first quantitative comparison of BODIPY and ORO for investigating exercise-induced changes in IMTG content and LD morphology on a fibre type and subcellular-specific basis. Estimates of IMTG content were greater when using BODIPY, which was predominantly due to BODIPY detecting a larger number of LDs, compared to ORO. The subcellular distribution of intramuscular lipid was also dependent on the lipid dye used; ORO detects a greater proportion of IMTG in the periphery (5 μm below cell membrane) of the fibre, whereas IMTG content was higher in the central region using BODIPY. In response to 60 min moderate-intensity cycling exercise, IMTG content was reduced in both the peripheral (- 24%) and central region (- 29%) of type I fibres (P < 0.05) using BODIPY, whereas using ORO, IMTG content was only reduced in the peripheral region of type I fibres (- 31%; P < 0.05). As well as highlighting some methodological considerations herein, our investigation demonstrates that important differences exist between BODIPY and ORO for detecting and quantifying IMTG on a fibre type and subcellular-specific basis