The block cipher NSABC (public domain)

We introduce NSABC/w -- Nice-Structured Algebraic Block Cipher using w-bit word arithmetic, a 4w-bit analogous of Skipjack [NSA98] with 5w-bit key. The Skipjack's internal 4-round Feistel structure is replaced with a w-bit, 2-round cascade of a binary operation (x,z)\mapsto(x\boxdot z)\lll(w/2) that permutes a text word x under control of a key word z. The operation \boxdot, similarly to the multiplication in IDEA [LM91, LMM91], bases on an algebraic group over w-bit words, so it is also capable of decrypting by means of the inverse element of z in the group. The cipher utilizes a secret 4w-bit tweak -- an easily changeable parameter with unique value for each block encrypted under the same key [LRW02] -- that is derived from the block index and an additional 4w -bit key. A software implementation for w=64 takes circa 9 clock cycles per byte on x86-64 processors.Comment: 22 pages, 4 figure

OPA1 mutation and late-onset cardiomyopathy: mitochondrial dysfunction and mtDNA instability.

BackgroundMitochondrial fusion protein mutations are a cause of inherited neuropathies such as Charcot-Marie-Tooth disease and dominant optic atrophy. Previously we reported that the fusion protein optic atrophy 1 (OPA1) is decreased in heart failure.Methods and resultsWe investigated cardiac function, mitochondrial function, and mtDNA stability in a mouse model of the disease with OPA1 mutation. The homozygous mutation is embryonic lethal. Heterozygous OPA(+/-) mice exhibit reduced mtDNA copy number and decreased expression of nuclear antioxidant genes at 3 to 4 months. Although initial cardiac function was normal, at 12 months the OPA1(+/-) mouse hearts had decreased fractional shortening, cardiac output, and myocyte contraction. This coincided with the onset of blindness. In addition to small fragmented mitochondria, aged OPA1(+/-) mice had impaired cardiac mitochondrial function compared with wild-type littermates.ConclusionsOPA1 mutation leads to deficiency in antioxidant transcripts, increased reactive oxygen species, mitochondrial dysfunction, and late-onset cardiomyopathy

Utilization of Molecular Inversion Probes in Malaria Sequencing

While massively parallel sequencing of whole genomes shed light on many previously puzzling genetic questions, the high costs associated with this approach makes its use impractical when large cohorts need to be sequenced at high coverage. Available capture technologies reduces the sequencing costs by enriching template material for the regions of interest. However, these technologies are also prohibitively costly at high sample numbers. Capture methods utilizing molecular inversion probes (MIPs) offer a flexible alternative to enrich template material that multiplex well for thousands of samples and require minimal resources. Here, for our work in malaria, we extend the utility of MIPs, improving the capture length and efficiency. We have also dramatically decreased the capture time from 24-48 h to 1 h. Combined, these improvements allow the potential for rapid and reliable application of MIP captures in research and, importantly, clinical settings

Drug-Resistance and Population Structure of Plasmodium falciparum Across the Democratic Republic of Congo Using High-Throughput Molecular Inversion Probes

A better understanding of the drivers of the spread of malaria parasites and drug resistance across space and time is needed. These drivers can be elucidated using genetic tools. Here, a novel molecular inversion probe (MIP) panel targeting all major drug-resistance mutations and a set of microsatellites was used to genotype Plasmodium falciparum infections of 552 children from the 2013-2014 Demographic and Health Survey conducted in the Democratic Republic of the Congo (DRC). Microsatellite-based analysis of population structure suggests that parasites within the DRC form a homogeneous population. In contrast, sulfadoxine-resistance markers in dihydropteroate synthase show marked spatial structure with ongoing spread of double and triple mutants compared with 2007. These findings suggest that parasites in the DRC remain panmictic despite rapidly spreading antimalarial-resistance mutations. Moreover, highly multiplexed targeted sequencing using MIPs emerges as a cost-effective method for elucidating pathogen genetics in complex infections in large cohorts

Mitigating The Burden Of Diabetes In Sub-Saharan Africa Through An Integrated Diagonal Health Systems Approach

Diabetes is a chronic non-communicable disease (NCD) presenting growing health and economic burdens in sub-Saharan Africa (SSA). Diabetes is unique due to its cross-cutting nature, impacting multiple organ systems and increasing the risk for other communicable and non-communicable diseases. Unfortunately, the quality of care for diabetes in SSA is poor, largely due to a weak disease management framework and fragmented health systems in most sub-Saharan African countries. We argue that by synergizing disease-specific vertical programs with system-specific horizontal programs through an integrated disease-system diagonal approach, we can improve access, quality, and safety of diabetes care programs while also supporting other chronic diseases. We recommend utilizing the six World Health Organization (WHO) health system building blocks – 1) leadership and governance, 2) financing, 3) health workforce, 4) health information systems, 5) supply chains, and 6) service delivery – as a framework to design a diagonal approach with a focus on health system strengthening and integration to implement and scale quality diabetes care. We discuss the successes and challenges of this approach, outline opportunities for future care programming and research, and highlight how this approach can lead to the improvement in the quality of care for diabetes and other chronic diseases across SSA

Reductions from module lattices to free module lattices, and application to dequantizing module-LLL

In this article, we give evidence that free modules (i.e., modules which admit a basis) are no weaker than arbitrary modules, when it comes to solving cryptographic algorithmic problems (and when the rank of the module is at least 2). More precisely, we show that for three algorithmic problems used in cryptography, namely the shortest vector problem, the Hermite shortest vector problem and a variant of the closest vector problem, there is a reduction from solving the problem in any module of rank $n ≥ 2$ to solving the problem in any free module of the same rank $n$. As an application, we show that this can be used to dequantize the LLL algorithm for module lattices presented by Lee et al. (Asiacrypt 2019)

Developing "smart" tutorial tools to assist students learn calculus, taking account of their changing preferred approaches to learning

We present the result of a small study where we investigate what types of resources current students of Mathematics and Mathematics for Engineering prefer for assisting them with their studies of those topics. We found that modern students seem to have a clear preference for on-line resources over traditional textbooks. However, there is currently a lack of good quality resources of that type which allow students to carry-out conventional mathematics exercises on-line and still get appropriate, meaningful and informative feedback on their answers. We then describe our efforts towards addressing this problem through the development of an “intelligent” tutorial system for Calculus which provides feedback tailored to the student’s responses, noting where and how they have made common errors

Deletion of the eIFiso4G subunit of the Arabidopsis eIFiso4F translation initiation complex impairs health and viability

Arabidopsis thaliana knockout lines for the plant-specific eukaryotic translation initiation factors eIFiso4G1 (i4g1) and eIFiso4G2 (i4g2) genes have been obtained. To address the potential for functional redundancy of these genes, homozygous double mutant lines were generated by crossing individual knockout lines. Both single and double mutant plants were analyzed for changes in gross morphology, development, and responses to selected environmental stressors. Single gene knockouts appear to have minimal effect on morphology, germination rate, growth rate, flowering time, or fertility. However, double mutant i4g1/i4g2 knockout plants show reduced germination rates, slow growth rates, moderate chlorosis, impaired fertility and reduced long term seed viability. Double mutant plants also exhibit altered responses to dehydration, salinity, and heat stress. The i4g2 and i4g1/i4g2 double mutant has reduced amounts of chlorophyll a and b suggesting a role in the expression of chloroplast proteins. General protein synthesis did not appear to be affected as the levels of gross protein expression did not appear to change in the mutants. The lack of a phenotype for either of the single mutants suggests there is considerable functional overlap. However, the strong phenotypes observed for the double mutant indicates that the individual gene products may have specialized roles in the expression of proteins involved in plant growth and development

Promoting early childhood development in Viet Nam: cost-effectiveness analysis alongside a cluster-randomised trial

Economic evaluations are critical to ensure effective resource use to implement and scale up child development interventions. This study aimed to estimate the cost-effectiveness of a multicomponent early childhood development intervention in rural Viet Nam. We did a cost-effectiveness study alongside a cluster-randomised trial with a 30-month time horizon. The study included 669 mothers from 42 communes in the intervention group, and 576 mothers from 42 communes in the control group. Mothers in the intervention group attended Learning Clubs sessions from mid-pregnancy to 12 months after delivery. The primary outcomes were child cognitive, language, motor, and social-emotional development at age 2 years. In this analysis, we estimated the incremental cost-effectiveness ratios (ICERs) of the intervention compared with the usual standard of care from the service provider and household perspectives. We used non-parametric bootstrapping to examine uncertainty, and applied a 3% discount rate. The total intervention cost was US$169 898 (start-up cost$133 692 and recurrent cost $36 206). The recurrent cost per child was$58 (1 341 741 Vietnamese dong). Considering the recurrent cost alone, the base-case ICER was $14 and mean ICER of 1000 bootstrap samples was$14 (95% CI -0·48 to 30) per cognitive development score gained with a 3% discount rate to costs. The ICER per language and motor development score gained was $22 and$20, respectively, with a 3% discount rate to costs. The intervention was cost-effective: the ICER per child cognitive development score gained was 0·5% of Viet Nam's gross domestic product per capita, alongside other benefits in language and motor development. This finding supports the scaling up of this intervention in similar socioeconomic settings. Australian National Health and Medical Research Council and Grand Challenges Canada. For the Vietnamese translation of the abstract see Supplementary Materials section

Evaluating the impact of curfews and other measures on SARS-CoV-2 transmission in French Guiana.

While general lockdowns have proven effective to control SARS-CoV-2 epidemics, they come with enormous costs for society. It is therefore essential to identify control strategies with lower social and economic impact. Here, we report and evaluate the control strategy implemented during a large SARS-CoV-2 epidemic in June-July 2020 in French Guiana that relied on curfews, targeted lockdowns, and other measures. We find that the combination of these interventions coincided with a reduction in the basic reproduction number of SARS-CoV-2 from 1.7 to 1.1, which was sufficient to avoid hospital saturation. We estimate that thanks to the young demographics, the risk of hospitalisation following infection was 0.3 times that of metropolitan France and that about 20% of the population was infected by July. Our model projections are consistent with a recent seroprevalence study. The study showcases how mathematical modelling can be used to support healthcare planning in a context of high uncertainty