Analysis of email and phone queuing systems in a world-wide contact center network

Thesis (M.B.A.)--Massachusetts Institute of Technology, Sloan School of Management; and, (S.M.)--Massachusetts Institute of Technology, Dept. of Aeronautics and Astronautics; in conjunction with the Leaders for Manufacturing Program at MIT, 2008.Includes bibliographical references (p. 50).Contact centers are operated by companies to answer customer inquiries via phone calls or email. Customers often equate the service they are provided while interacting with a contact center to the quality of a company's product offering. Therefore, a major concern is what service level the company should choose to provide. One means of measuring service level is speed of response (how quickly a customer inquiry is answered). In general, faster response requires more customer service agents for a given volume of inquiries. Phone response times are usually measured in minutes or seconds. Email response times are usually measured in hours or days. This paper examines customer expectations regarding email and phone inquiry response time, and examines various models for planning staffing requirements to meet these response times. The expectations for response time to phone calls are found to be stable, having not changed much in the last few decades. The expectations for response time to email inquiries have been increasing though, with customers demanding much faster response in the last few years. Many customers now expect response to their emails within hours rather than days, with a significant number now expecting response as quickly as one hour. The challenges of implementing faster response times to email are examined using a case study at a major online retailer. A model is also introduced for email service level planning, that allows for the fact that typical response times are much longer than for phone calls.by Kristopher Carter.S.M.M.B.A

DNA Damage Response and Repair: Insights into Strategies for Radiation Sensitization

The incorporation of radiotherapy into multimodality treatment plans has led to significant improvements in glioma patient survival. However, local recurrence from glioma resistance to ionizing radiation remains a therapeutic challenge. The tumoricidal effect of radiation therapy is largely attributed to the induction of dsDNA breaks (DSBs). In the past decade, there have been tremendous strides in understanding the molecular mechanisms underlying DSB repair. The identification of gene products required for DSB repair has provided novel therapeutic targets. Recent studies revealed that many US FDA-approved cancer agents inhibit DSB repair by interacting with repair proteins. This article will aim to provide discussion of DSB repair mechanisms to provide molecular targets for radiation sensitization of gliomas and a discussion of FDA-approved cancer therapies that modulate DSB repair to highlight opportunities for combination therapy with radiotherapy for glioma therapy

Multiomic analyses implicate a neurodevelopmental program in the pathogenesis of cerebral arachnoid cysts

Cerebral arachnoid cysts (ACs) are one of the most common and poorly understood types of developmental brain lesion. To begin to elucidate AC pathogenesis, we performed an integrated analysis of 617 patient-parent (trio) exomes, 152,898 human brain and mouse meningeal single-cell RNA sequencing transcriptomes and natural language processing data of patient medical records. We found that damaging de novo variants (DNVs) were highly enriched in patients with ACs compared with healthy individuals (P = 1.57 × 10-33). Seven genes harbored an exome-wide significant DNV burden. AC-associated genes were enriched for chromatin modifiers and converged in midgestational transcription networks essential for neural and meningeal development. Unsupervised clustering of patient phenotypes identified four AC subtypes and clinical severity correlated with the presence of a damaging DNV. These data provide insights into the coordinated regulation of brain and meningeal development and implicate epigenomic dysregulation due to DNVs in AC pathogenesis. Our results provide a preliminary indication that, in the appropriate clinical context, ACs may be considered radiographic harbingers of neurodevelopmental pathology warranting genetic testing and neurobehavioral follow-up. These data highlight the utility of a systems-level, multiomics approach to elucidate sporadic structural brain disease

The state of the Martian climate

60°N was +2.0°C, relative to the 1981–2010 average value (Fig. 5.1). This marks a new high for the record. The average annual surface air temperature (SAT) anomaly for 2016 for land stations north of starting in 1900, and is a significant increase over the previous highest value of +1.2°C, which was observed in 2007, 2011, and 2015. Average global annual temperatures also showed record values in 2015 and 2016. Currently, the Arctic is warming at more than twice the rate of lower latitudes

Craniectomy for Malignant Cerebral Infarction: Prevalence and Outcomes in US Hospitals

Randomized trials have demonstrated the efficacy of craniectomy for the treatment of malignant cerebral edema following ischemic stroke. We sought to determine the prevalence and outcomes related to this by using a national database.Patient discharges with ischemic stroke as the primary diagnosis undergoing craniectomy were queried from the US Nationwide Inpatient Sample from 1999 to 2008. A subpopulation of patients was identified that underwent thrombolysis. Two primary end points were examined: in-hospital mortality and discharge to home/routine care. To facilitate interpretations, adjusted prevalence was calculated from the overall prevalence and two age-specific logistic regression models. The predictive margin was then generated using a multivariate logistic regression model to estimate the probability of in-hospital mortality after adjustment for admission type, admission source, length of stay, total hospital charges, chronic comorbidities, and medical complications.After excluding 71,996 patients with the diagnosis of intracranial hemorrhage and posterior intracranial circulation occlusion, we identified 4,248,955 adult hospitalizations with ischemic stroke as a primary diagnosis. The estimated rates of hospitalizations in craniectomy per 10,000 hospitalizations with ischemic stroke increased from 3.9 in 1999-2000 to 14.46 in 2007-2008 (p for linear trend<0.001). Patients 60+ years of age had in-hospital mortality of 44% while the 18-59 year old group was found to be 24% (p = 0.14). Outcomes were comparable if recombinant tissue plasminogen activator had been administered.Craniectomy is being increasingly performed for malignant cerebral edema following large territory cerebral ischemia. We suspect that the increase in the annual incidence of DC for malignant cerebral edema is directly related to the expanding collection of evidence in randomized trials that the operation is efficacious when performed in the correct patient population. In hospital mortality is high for all patients undergoing this procedure

Insights into the Ecology and Evolutionary Success of Crocodilians Revealed through Bite-Force and Tooth-Pressure Experimentation

BackgroundCrocodilians have dominated predatory niches at the water-land interface for over 85 million years. Like their ancestors, living species show substantial variation in their jaw proportions, dental form and body size. These differences are often assumed to reflect anatomical specialization related to feeding and niche occupation, but quantified data are scant. How these factors relate to biomechanical performance during feeding and their relevance to crocodilian evolutionary success are not known.Methodology/Principal FindingsWe measured adult bite forces and tooth pressures in all 23 extant crocodilian species and analyzed the results in ecological and phylogenetic contexts. We demonstrate that these reptiles generate the highest bite forces and tooth pressures known for any living animals. Bite forces strongly correlate with body size, and size changes are a major mechanism of feeding evolution in this group. Jaw shape demonstrates surprisingly little correlation to bite force and pressures. Bite forces can now be predicted in fossil crocodilians using the regression equations generated in this research.Conclusions/SignificanceCritical to crocodilian long-term success was the evolution of a high bite-force generating musculo-skeletal architecture. Once achieved, the relative force capacities of this system went essentially unmodified throughout subsequent diversification. Rampant changes in body size and concurrent changes in bite force served as a mechanism to allow access to differing prey types and sizes. Further access to the diversity of near-shore prey was gained primarily through changes in tooth pressure via the evolution of dental form and distributions of the teeth within the jaws. Rostral proportions changed substantially throughout crocodilian evolution, but not in correspondence with bite forces. The biomechanical and ecological ramifications of such changes need further examination

Ribosome-Associated Vesicles promote activity-dependent local translation

Local protein synthesis in axons and dendrites underpins synaptic plasticity. However, the composition of the protein synthesis machinery in distal neuronal processes and the mechanisms for its activity-driven deployment to local translation sites remain unclear. Here, we employed cryo-electron tomography, volume electron microscopy, and live-cell imaging to identify Ribosome-Associated Vesicles (RAVs) as a dynamic platform for moving ribosomes to distal processes. Stimulation via chemically-induced long-term potentiation causes RAV accumulation in distal sites to drive local translation. We also demonstrate activity-driven changes in RAV generation and dynamics , identifying tubular ER shaping proteins in RAV biogenesis. Together, our work identifies a mechanism for ribosomal delivery to distal sites in neurons to promote activity-dependent local translation

Global, regional, and national burden of tuberculosis, 1990–2016: results from the Global Burden of Diseases, Injuries, and Risk Factors 2016 Study

Background Although a preventable and treatable disease, tuberculosis causes more than a million deaths each year. As countries work towards achieving the Sustainable Development Goal (SDG) target to end the tuberculosis epidemic by 2030, robust assessments of the levels and trends of the burden of tuberculosis are crucial to inform policy and programme decision making. We assessed the levels and trends in the fatal and non-fatal burden of tuberculosis by drug resistance and HIV status for 195 countries and territories from 1990 to 2016. Methods We analysed 15 943 site-years of vital registration data, 1710 site-years of verbal autopsy data, 764 site-years of sample-based vital registration data, and 361 site-years of mortality surveillance data to estimate mortality due to tuberculosis using the Cause of Death Ensemble model. We analysed all available data sources, including annual case notifications, prevalence surveys, population-based tuberculin surveys, and estimated tuberculosis cause-specific mortality to generate internally consistent estimates of incidence, prevalence, and mortality using DisMod-MR 2.1, a Bayesian meta-regression tool. We assessed how the burden of tuberculosis differed from the burden predicted by the Socio-demographic Index (SDI), a composite indicator of income per capita, average years of schooling, and total fertility rate. Findings Globally in 2016, among HIV-negative individuals, the number of incident cases of tuberculosis was 9·02 million (95% uncertainty interval [UI] 8·05–10·16) and the number of tuberculosis deaths was 1·21 million (1·16–1·27). Among HIV-positive individuals, the number of incident cases was 1·40 million (1·01–1·89) and the number of tuberculosis deaths was 0·24 million (0·16–0·31). Globally, among HIV-negative individuals the age-standardised incidence of tuberculosis decreased annually at a slower rate (–1·3% [–1·5 to −1·2]) than mortality did (–4·5% [–5·0 to −4·1]) from 2006 to 2016. Among HIV-positive individuals during the same period, the rate of change in annualised age-standardised incidence was −4·0% (–4·5 to −3·7) and mortality was −8·9% (–9·5 to −8·4). Several regions had higher rates of age-standardised incidence and mortality than expected on the basis of their SDI levels in 2016. For drug-susceptible tuberculosis, the highest observed-to-expected ratios were in southern sub-Saharan Africa (13·7 for incidence and 14·9 for mortality), and the lowest ratios were in high-income North America (0·4 for incidence) and Oceania (0·3 for mortality). For multidrug-resistant tuberculosis, eastern Europe had the highest observed-to-expected ratios (67·3 for incidence and 73·0 for mortality), and high-income North America had the lowest ratios (0·4 for incidence and 0·5 for mortality). Interpretation If current trends in tuberculosis incidence continue, few countries are likely to meet the SDG target to end the tuberculosis epidemic by 2030. Progress needs to be accelerated by improving the quality of and access to tuberculosis diagnosis and care, by developing new tools, scaling up interventions to prevent risk factors for tuberculosis, and integrating control programmes for tuberculosis and HIV

Trends in HIV/AIDS morbidity and mortality in Eastern 3 Mediterranean countries, 1990–2015: findings from the Global 4 Burden of Disease 2015 study

Objectives We used the results of the Global Burden of Disease 2015 study to estimate trends of HIV/AIDS burden in Eastern Mediterranean Region (EMR) countries between 1990 and 2015. Methods Tailored estimation methods were used to produce final estimates of mortality. Years of life lost (YLLs) were calculated by multiplying the mortality rate by population by age-specific life expectancy. Years lived with disability (YLDs) were computed as the prevalence of a sequela multiplied by its disability weight. Results In 2015, the rate of HIV/AIDS deaths in the EMR was 1.8 (1.4–2.5) per 100,000 population, a 43% increase from 1990 (0.3; 0.2–0.8). Consequently, the rate of YLLs due to HIV/AIDS increased from 15.3 (7.6–36.2) per 100,000 in 1990 to 81.9 (65.3–114.4) in 2015. The rate of YLDs increased from 1.3 (0.6–3.1) in 1990 to 4.4 (2.7–6.6) in 2015. Conclusions HIV/AIDS morbidity and mortality increased in the EMR since 1990. To reverse this trend and achieve epidemic control, EMR countries should strengthen HIV surveillance,and scale up HIV antiretroviral therapy and comprehensive prevention services