DSPatch: Dual Spatial Pattern Prefetcher

High main memory latency continues to limit performance of modern high-performance out-of-order cores. While DRAM latency has remained nearly the same over many generations, DRAM bandwidth has grown significantly due to higher frequencies, newer architectures (DDR4, LPDDR4, GDDR5) and 3D-stacked memory packaging (HBM). Current state-of-the-art prefetchers do not do well in extracting higher performance when higher DRAM bandwidth is available. Prefetchers need the ability to dynamically adapt to available bandwidth, boosting prefetch count and prefetch coverage when headroom exists and throttling down to achieve high accuracy when the bandwidth utilization is close to peak. To this end, we present the Dual Spatial Pattern Prefetcher (DSPatch) that can be used as a standalone prefetcher or as a lightweight adjunct spatial prefetcher to the state-of-the-art delta-based Signature Pattern Prefetcher (SPP). DSPatch builds on a novel and intuitive use of modulated spatial bit-patterns. The key idea is to: (1) represent program accesses on a physical page as a bit-pattern anchored to the first "trigger" access, (2) learn two spatial access bit-patterns: one biased towards coverage and another biased towards accuracy, and (3) select one bit-pattern at run-time based on the DRAM bandwidth utilization to generate prefetches. Across a diverse set of workloads, using only 3.6KB of storage, DSPatch improves performance over an aggressive baseline with a PC-based stride prefetcher at the L1 cache and the SPP prefetcher at the L2 cache by 6% (9% in memory-intensive workloads and up to 26%). Moreover, the performance of DSPatch+SPP scales with increasing DRAM bandwidth, growing from 6% over SPP to 10% when DRAM bandwidth is doubled.Comment: This work is to appear in MICRO 201

Stage of Disease and Likelihood of Surgical Intervention in Colon Cancer Patients: An Exploratory Analysis of the SEER Database

Introduction/Objectives: Colorectal cancer (CRC) remains as the third-leading cause of cancer-related deaths amongst both men and women in the United States. However, the mortality rate from CRC continues to drop, which has been attributed to increased surgical polyp removal. This study explored the association between disease stage and the likelihood of surgical intervention as primary treatment for the disease. Methods: Retrospective cohort study analysis using de-identified patient data from the NCI’s Surveillance, Epidemiology, and End Results (SEER) database from 1998-2015. Inclusion criteria included patients with colon cancer, over 18 years of age, with known disease in either the proximal or distal colon. Patients with rectal cancer were excluded given that surgery is not indicated for lesions in that site. Results: Multivariate analysis results indicated that patients with regional disease are between 4-5 times as likely to receive primary surgical intervention in comparison to those with localized disease (OR=4.557, 95% CI=4.295, 4.835). Distant stage of disease was associated with a significantly decreased likelihood of receiving surgery in comparison to localized stage of disease (OR=0.118, CI=0.114, 0.122). Other factors significantly associated with an increased likelihood of surgical intervention (in descending order) included mucinous adenocarcinoma histology, papillary adenocarcinoma histology, having a partner, adenomatous polyps on histology, white ethnicity, female sex, and lesion location in the proximal colon. Conclusion: It was found that stage at diagnosis was far more predictive of surgical treatment than any of the other variables examined. This finding highlights the important for screening in order to identify operable disease

Factors Associated with Stage at Presentation Among Patients with Rare Pancreatic Tumors: An Exploratory Analysis of the SEER Database

Introduction: Rare pancreatic carcinomas (PC) account for roughly 15% of all pancreatic cancers and approximately 8,300 new cases within the US annually. Little research compares initial stage at diagnosis among rare vs. common pancreatic tumors. The aim of this study was to examine associations between tumor histology and initial stage at diagnosis among cases of rare pancreatic cancers. Methods: Retrospective cohort study, using the NCI’s Surveillance, Epidemiology, and End Results (SEER) 1990-2015 database. We included patients diagnosed with pancreatic cancer aged 18+. Histology was classified into four categories (ductal, carcinoid, mucinous adenocarcinoma, and undetermined) and stage was dichotomized (locoregional versus distant). Multivariate logistic regression was used to describe the association between tumor histology with initial stage at diagnosis, controlling for patient and tumor characteristics. Results: 90,764 PC patients were analyzed: 9.60%(ductal carcinomas), 4.47%(carcinoid), 3.78%(mucinous), and 15.81%(undetermined); 54.74% of cases were distantly metastasized at diagnosis. In multivariate analysis, PC patients with mucinous histology had greater odds of presenting with late-stage disease compared to those with adenocarcinoma (OR=141%,CI=131,152%; carcinoid and undetermined neoplasm findings were not significant (OR=99.1%CI=92.3,106.5% and OR=101.3%Cl=97.3%,105.4% respectively). Other factors associated with distant PC included age 40-59, male sex, and African American background. Discussion: We observed that mucinous histology has a greater risk of late-stage diagnosis while carcinoid and undetermined neoplasms had a similar risk of late-stage diagnosis vs. adenocarcinoma

Child wasting and concurrent stunting in low- and middle-income countries

Sustainable Development Goal 2.2—to end malnutrition by 2030—includes the elimination of child wasting, defined as a weight-for-length z-score that is more than two standard deviations below the median of the World Health Organization standards for child growth 1. Prevailing methods to measure wasting rely on cross-sectional surveys that cannot measure onset, recovery and persistence—key features that inform preventive interventions and estimates of disease burden. Here we analyse 21 longitudinal cohorts and show that wasting is a highly dynamic process of onset and recovery, with incidence peaking between birth and 3 months. Many more children experience an episode of wasting at some point during their first 24 months than prevalent cases at a single point in time suggest. For example, at the age of 24 months, 5.6% of children were wasted, but by the same age (24 months), 29.2% of children had experienced at least one wasting episode and 10.0% had experienced two or more episodes. Children who were wasted before the age of 6 months had a faster recovery and shorter episodes than did children who were wasted at older ages; however, early wasting increased the risk of later growth faltering, including concurrent wasting and stunting (low length-for-age z-score), and thus increased the risk of mortality. In diverse populations with high seasonal rainfall, the population average weight-for-length z-score varied substantially (more than 0.5 z in some cohorts), with the lowest mean z-scores occurring during the rainiest months; this indicates that seasonally targeted interventions could be considered. Our results show the importance of establishing interventions to prevent wasting from birth to the age of 6 months, probably through improved maternal nutrition, to complement current programmes that focus on children aged 6–59 months

Early-childhood linear growth faltering in low- and middle-income countries

Globally, 149 million children under 5 years of age are estimated to be stunted (length more than 2 standard deviations below international growth standards) 1,2. Stunting, a form of linear growth faltering, increases the risk of illness, impaired cognitive development and mortality. Global stunting estimates rely on cross-sectional surveys, which cannot provide direct information about the timing of onset or persistence of growth faltering—a key consideration for defining critical windows to deliver preventive interventions. Here we completed a pooled analysis of longitudinal studies in low- and middle-income countries (n = 32 cohorts, 52,640 children, ages 0–24 months), allowing us to identify the typical age of onset of linear growth faltering and to investigate recurrent faltering in early life. The highest incidence of stunting onset occurred from birth to the age of 3 months, with substantially higher stunting at birth in South Asia. From 0 to 15 months, stunting reversal was rare; children who reversed their stunting status frequently relapsed, and relapse rates were substantially higher among children born stunted. Early onset and low reversal rates suggest that improving children’s linear growth will require life course interventions for women of childbearing age and a greater emphasis on interventions for children under 6 months of age

Causes and consequences of child growth faltering in low-resource settings

Growth faltering in children (low length for age or low weight for length) during the first 1,000 days of life (from conception to 2 years of age) influences short-term and long-term health and survival 1,2. Interventions such as nutritional supplementation during pregnancy and the postnatal period could help prevent growth faltering, but programmatic action has been insufficient to eliminate the high burden of stunting and wasting in low- and middle-income countries. Identification of age windows and population subgroups on which to focus will benefit future preventive efforts. Here we use a population intervention effects analysis of 33 longitudinal cohorts (83,671 children, 662,763 measurements) and 30 separate exposures to show that improving maternal anthropometry and child condition at birth accounted for population increases in length-for-age z-scores of up to 0.40 and weight-for-length z-scores of up to 0.15 by 24 months of age. Boys had consistently higher risk of all forms of growth faltering than girls. Early postnatal growth faltering predisposed children to subsequent and persistent growth faltering. Children with multiple growth deficits exhibited higher mortality rates from birth to 2 years of age than children without growth deficits (hazard ratios 1.9 to 8.7). The importance of prenatal causes and severe consequences for children who experienced early growth faltering support a focus on pre-conception and pregnancy as a key opportunity for new preventive interventions

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

Applied Physics of Carbon Nanotubes: Fundamentals of Theory, Optics and Transport Devices

The book describes the state-of-the-art in fundamental, applied and device physics of nanotubes, including fabrication, manipulation and characterization for device applications; optics of nanotubes; transport and electromechanical devices and fundamentals of theory for applications. This information is critical to the field of nanoscience since nanotubes have the potential to become a very significant electronic material for decades to come. The book will benefit all all readers interested in the application of nanotubes, either in their theoretical foundations or in newly developed characterization tools that may enable practical device fabrication