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Final Project for INST490: Integrated Capstone for Information Science (Spring 2021). University of Maryland, College Park., New Windsor, Maryland is seeking to install upgrades to town infrastructure; accomplishing this would have significant costs. Based on preliminary projections, there is potential for growth over the next 20-30 years, and it is important to consider that this growth could bring in new revenue. New Windsor has commissioned seniors in the University of Maryland’s Information Science program, through the PALS program, to complete a fiscal analysis of growth and revenue. Through collaboration between the UMD team, the New Windsor Mayor and Council, the PALS program, and the subject matter expert from BAE Urban Economics, the UMD team seeks to provide the town of New Windsor with a fiscal impact analysis that will project the expected impact of growth in the town, and if that growth will offset the costs of planned infrastructure improvements.

Highlights • Model developed to assess impact of seasonality on Ascaris lumbricoides infections. • Analytical expressions relate egg and worm numbers to seasonal variations. • Reduction in seasonal perturbation through the life cycle. • Utilising seasonality for optimal timing of annual treatment has profound benefits. • Exploit seasonality to reduce number of treatment rounds for local elimination., Intestinal nematode infections affect a huge proportion of the world’s population. Increasingly these infections, particularly amongst the poorest communities, are controlled through mass drug treatment programs. Seasonal variations of climate and behaviour in these regions can be significant, but their impact on the dynamics of infection and implications for the effectiveness of any mass drug treatment program (a pulsed reduction in worm burden in hosts) is not clearly understood. Here the effect of seasonality on the dynamics of the soil-based helminth, Ascaris lumbricoides, is investigated using a reformulated version of the Anderson–May model for macro-parasitic infections. Explicit analytical expressions are obtained for the stable oscillatory solution over the annual cycle, which provides a means of relating times of peak numbers of eggs, larvae and mature worms to seasonal variations. Numerical and analytical techniques are then used to consider the impact of seasonality on the optimal timing of drug treatment. Our results show that there is a relatively large window for the timing of optimal treatment, and the impact of repeated annual mass drug treatments can be substantially improved if they are timed to coincide with the months when the number of eggs and larvae are at their lowest - minimising reinfection. In terms of a more measurable quantity, in our example this corresponds to the months when the seasonal temperature is highest. Multiple annual treatments at (or close to) the optimal time each year are predicted to achieve local elimination in the community, whereas treatment at other times has a more limited impact. A key finding is that even for pronounced seasonality, perturbations in mean worm burden, and hence seasonal variation in observed egg output, may be small, potentially explaining why seasonal effects have been overlooked. Taken together these results suggest that seasonality of soil-transmitted helminths requires further experimental, field and mathematical study if the impact for mass drug administration programs is to be exploited.

Background: High sedentary time is associated with adverse metabolic health outcomes and mortality in older adults. It has been suggested that breaking up sedentary time may be beneficial for metabolic health; however, population prevalence data are lacking on the patterns of sedentary behaviour which would identify opportunities for intervention. Methods: We used data of adults aged ≥ 60 years (n = 3705) from the population-based EPIC-Norfolk cohort, to characterize the patterns of total sedentary time, breaks in sedentary time and sedentary bouts across the day and assess their associations with participant characteristics, using multi-level regression. Sedentary time was measured objectively by a hip-mounted accelerometer (Actigraph™ GT1M) worn for 7 days during waking time. Results: More than 50% of every waking hour was spent sedentary, increasing to a peak of 83% in the evening. On average fewer breaks were accrued in the evenings compared with earlier in the day. Marginally more sedentary time was accrued on weekend days compared with weekdays (difference 7.4 min, 95% confidence interval 5.0–9.7). Large proportions of this sedentary time appear to be accrued in short bouts (bouts of < 10 min for 32% of the time). Older age, being male, being retired, not being in paid employment and having a higher body mass index were associated with greater sedentary time and fewer breaks. Conclusion: Sedentary time is common throughout the day but peaks in the evenings with fewer breaks and longer bouts. We identified a number of characteristics associated with sedentary time and additionally inversely associated with sedentary breaks, which should inform the development and targeting of strategies to reduce sedentary time among older adults.

This paper describes the case of a non diabetic physician with a prior psychiatric history in which there was overwhelming biochemical and clinical evidence that he had attempted suicide by injecting himself with an overdose of insulin. He was extensively monitored from the time of his admission to hospital in a coma, until he fully recovered consciousness 30 days later and during the next eight months of his rehabilitation. This case attests to the high level of morbidity which might follow profound hypoglycemia. It also illustrates some putative psychodynamics of suicidal behaviour — notably ambivalence and denial (at the time of writing, the patient never acknowledged that he had overdosed with insulin). A selective review on some of the more recent literature on the neuropathological effects of insulin overdose and profound hypoglycemia is presented.

Comment on: Autoerotic asphyxial deaths: analysis of nineteen fatalities in Alberta, 1978 to 1989.Tough SC, Butt JC, Sanders GL. Can J Psychiatry. 1994 Apr; 39(3):157-60. Language: en

The radiation-sensitive rad mutants of the yeast Saccharomyces cerevisiae exhibit a complex pattern of sensitivity to simple monofunctional alkylating agents. The RAD1, RAD2, RAD4 and RAD14 genes of the RAD3 epistasis group are implicated in the repair of ethylations to DNA. The RAD3, RAD10 and RAD16 genes of this group are not involved. The RAD4 and RAD14 genes have a particular role in repair following exposure to those ethylating agents that preferentially alkylate oxygen, but not to those that preferentially ethylate nitrogen. The RAD1 and RAD2 genes are involved in the repair of damage induced by all the ethylating agents used except EMS. The mutants in this group that are sensitive to ENU were not sensitive to MNU, suggesting that nucleotide excision operates on ethylations but not on methylations. In the RAD6 group, the RAD6 and RAD18 genes are involved in DNA repair after exposure to all the alkylating agents tested, whereas RAD8 appears to have a role in the repair of O-alkylations but not N-alkylations. RAD9 operates in the repair of methylations and ethylations, but does not influence events after exposure to EMS. In the RAD52 group, the mutants tested were sensitive to ENU and DES. Thus some members of all three epistasis groups are involved in the repair of alkylations to DNA.

The cheese reaction following use of the irreversible monoamine oxidase inhibitors (MAOIs) began to be reported in the UK with increasing frequency from about 1961. By 1965, the underlying mechanism (tyramine-provoked hypertension) had been essentially elucidated. Thereafter, this potentially severe side-effect could have been largely avoided by the use of fairly simple dietary precautions. Unfortunately, suspicion and fear burgeoned, and both the seriousness and the frequency of risk were dramatically inflated. This was a major factor in the subsequent general disuse of the irreversible MAOIs. Second-generation MAOIs which are selective for monoamine oxidase-A and B are now being synthesised and may eliminate the eventuality of hypertension without special dietary precautions.

Article de synthese sur les mecanismes de reparation de l'ADN chez S. cerevisiae comprenant les mecanismes de reaction induits par les UV et les genes impliques dans la reparation a l'obscurite, formant les groupes epistatiques RAD3, RAD6 et RAD52

Fruit and vegetable intake (FVI) may reduce the risk of type 2 diabetes (T2D), but the epidemiological evidence is inconclusive. The aim of this study is to examine the prospective association of FVI with T2D and conduct an updated meta-analysis. In the European Prospective Investigation into Cancer-InterAct (EPIC-InterAct) prospective case-cohort study nested within eight European countries, a representative sample of 16 154 participants and 12 403 incident cases of T2D were identified from 340 234 individuals with 3.99 million person-years of follow-up. For the meta-analysis we identified prospective studies on FVI and T2D risk by systematic searches of MEDLINE and EMBASE until April 2011. In EPIC-InterAct, estimated FVI by dietary questionnaires varied more than twofold between countries. In adjusted analyses the hazard ratio (95% confidence interval) comparing the highest with lowest quartile of reported intake was 0.90 (0.80-1.01) for FVI; 0.89 (0.76-1.04) for fruit and 0.94 (0.84-1.05) for vegetables. Among FV subtypes, only root vegetables were inversely associated with diabetes 0.87 (0.77-0.99). In meta-analysis using pooled data from five studies including EPIC-InterAct, comparing the highest with lowest category for FVI was associated with a lower relative risk of diabetes (0.93 (0.87-1.00)). Fruit or vegetables separately were not associated with diabetes. Among FV subtypes, only green leafy vegetable (GLV) intake (relative risk: 0.84 (0.74-0.94)) was inversely associated with diabetes. Subtypes of vegetables, such as root vegetables or GLVs may be beneficial for the prevention of diabetes, while total FVI may exert a weaker overall effect.European Journal of Clinical Nutrition advance online publication, 1 August 2012; doi:10.1038/ejcn.2012.85.

At least eight neurodegenerative diseases, including Huntington disease, are caused by expansions in (CAG)n repeats in the affected gene and by an increase in the size of the corresponding polyglutamine domain in the expressed protein. A hallmark of several of these diseases is the presence of aberrant, proteinaceous aggregates in the nuclei and cytosol of affected neurons. Recent studies have shown that expanded polyglutamine (Qn) repeats are excellent glutaminyl-donor substrates of tissue transglutaminase, and that the substrate activity increases with increasing size of the polyglutamine domain. Tissue transglutaminase is present in the cytosol and nuclear fractions of brain tissue. Thus, the nuclear and cytosolic inclusions in Huntington disease may contain tissue transglutaminase-catalyzed covalent aggregates. The (CAG)n/Qn-expansion diseases are classic examples of selective vulnerability in the nervous system, in which certain cells/structures are particularly susceptible to toxic insults. Quantitative differences in the distribution of the brain transglutaminase(s) and its substrates, and in the activation mechanism of the brain transglutaminase(s), may explain in part selective vulnerability in a subset of neurons in (CAG)n-expansion diseases, and possibly in other neurodegenerative disease. If tissue transglutaminase is found to be essential for development of pathogenesis, then inhibitors of this enzyme may be of therapeutic benefit.

Protein aggregates are a hallmark of Huntington's disease (HD) and other inherited neurodegenerative diseases caused by an elongated (CAG)(n) repeat in the genome and to a corresponding increase in the size of the Q(n) domain in the expressed protein. When the protein associated with HD (huntingtin) contains35 Q repeats disease does not occur. However, an n/=40 leads to disease. Some investigators have proposed that aggregates in the nuclei of affected cells are toxic, but other workers have suggested that the aggregates may be neutral or even protective. Whether or not they are toxic, an understanding of the processes whereby the aggregates develop may shed light on the neuropathological processes involved in the (CAG)(n)/Q(n)-expansion disorders. Q(n) domains have a tendency to non-covalently self align as 'polar zippers' rendering them less soluble, but evidence that such polar zippers occur in the aggregates in intact HD brain has so far been limited. The human brain contains at least three Ca(2+)-dependent enzymes (transglutaminases, TGases) that catalyze protein cross-linking reactions, namely TGase 1, TGase 2 (tissue transglutaminase, tTGase) and TGase 3. Q(n) aggregates have been found by several groups to be excellent substrates of tTGase. Moreover, the activity toward the Q(n) domains increases greatly as n is increased to 40 or beyond. tTGase mRNA and total TGase activity are elevated in HD brain. Moreover, some evidence suggests that Ca(2+) homeostasis is disrupted in HD brain. We propose that the combination of increased huntingtin (or huntingtin fragment containing the Q(n) domain) in the nucleus, increased the ability of the Q(n) domains to act as substrate, increased Ca(2+) levels and increased inherent TGase activity all contribute to increased cross-linking of proteins in HD brain. At first the proteasome machinery can recognize and degrade the cross-linked proteins, but over time the proteasome machinery may be overwhelmed and protein aggregates will accumulate.

To investigate possible biochemical mechanisms underlying the ‘‘toxic gain of function’’ associated with polyglutamine expansions, the ability of guinea pig liver tissue transglutaminase to catalyze covalent attachments of various polyamines to polyglutamine peptides was examined. Of the polyamines tested, spermine is the most active substrate, followed by spermidine and putrescine. Formation of covalent cross links between polyglutamine peptides and polyamines yields high-Mr aggregates—a process that is favored with longer polyglutamines. In the presence of tissue transglutaminase, purified glyceraldehyde-3phosphate dehydrogenase (a key glycolytic enzyme that binds tightly to the polyglutamine domains of both huntingtin and dentatorubral‐pallidoluysian atrophy proteins) is covalently attached to polyglutamine peptides in vitro, resulting in the formation of high-Mr aggregates. In addition, endogenous glyceraldehyde-3-phosphate dehydrogenase of a Balb-c 3T3 fibroblast cell line overexpressing human tissue transglutaminase forms cross-links with a Q60 polypeptide added to the cell homogenate. Possibly, expansion of polyglutamine domains (thus far known to occur in the gene products associated with at least seven neurodegenerative diseases) leads to increased/aberrant tissue transglutaminase-catalyzed cross-linking reactions with both polyamines and susceptible proteins, such as glyceraldehyde-3-phosphate dehydrogenase. Formation of cross-linked heteropolymers may lead to deposition of high-Mr protein aggregates, thereby contributing to cell death. © 1998 Academic Press