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International audience; Objectives: Our aim was to assess if switching from a protease inhibitors (PI)-based regimen to a PI-free one is associated with an increased risk of Kaposi Sarcoma (KS) relapse among patients living with HIV (PLHIV) with history of KS and controlled HIV replication.Methods: In a retrospective analysis of the prospectively collected Dat'AIDS database we selected patients who both had a past KS history and a HIV-1 viral load below 200 copies/mL while being PI-treated. We searched for KS relapses while persistent virological success was maintained for at least 6 months, whether patients kept taking the PI, or switched to PI-free regimen.Results: Among the 216 patients with past KS event and a history of HIV-1 infection efficiently treated by a PI-based regimen, 148 patients (68.5%) later switched to a PI-sparing regimen. Their baseline characteristics were not different from non-switching patients. We described 7 cases of relapse (3.2% of the 216 patients). Five cases of relapse occurred in switching patients (3.4%). The remaining two relapses occurred in PI-treated patients (2.9%). At KS relapse, CD4 cell count was 459 cells/μL (range 225-560) for switching patients, compared with 362 and 136 cells/μL for the other two patients.Conclusions: In this large cohort of PLHIV with a history of KS and ART-controlled HIV replication, KS relapses were described in 3.2% of the patients, and were not more frequent when a PI-containing ART regimen has been switched to a PI-free regimen. Our results do not support a specific effect of PI on KS.

Background/Aims Urea cycle disorders (UCDs) are rare inborn errors of urea synthesis. US and European consensus statements on the diagnosis and treatment of UCDs were last published in 2001 and 2019, respectively. Recommendations are based primarily on case reports and expert opinion and there is limited agreement or consistency related to long-term management approaches. A clinician survey was conducted to assess current real-world practices and perspectives on challenges and unmet needs. Methods A 14-item multiple-choice survey was administered to physicians in 2017. Clinicians who reported actively managing at least 1 patient with UCD were eligible to participate. Descriptive statistics were calculated for each survey item (frequencies for categorical variables; means, standard deviations, medians, and ranges for continuous variables). Results Sixty-six US clinicians completed the survey (65 geneticists; 1 pediatric neurologist). Over 90% of responders agreed or strongly agreed that even modest elevations in ammonia could cause physiological and functional brain damage; >80% of respondents agreed that asymptomatic UCD patients are at risk of brain damage over time due to mild/subclinical elevations in ammonia. Eighty-six percent of clinicians agreed or strongly agreed with recommending genetic testing for female relatives when a patient is diagnosed with ornithine transcarbamylase deficiency. Ninety-four percent of respondents agreed that patients have better disease control when they are more adherent to their UCD therapy. Nearly 90% indicated that clinicians and patients would benefit from updated UCD management guidance. More than half (53%) of respondents rated the symptoms of UCDs as extremely or very burdensome to the everyday lives of patients and their families; only 8% rated UCD symptoms as slightly or not at all burdensome. The majority of clinicians agreed (48%) or strongly agreed (32%) that caring for a child or family member with a UCD has a negative impact on the quality of life and/or health of family members/guardians (e.g. stress, relationships, ability to work). Conclusions This self-reported survey suggests a need for updated and expanded clinical guidance on the long-term treatment and management of UCD patients.

Background. In the Long-Acting Antiretroviral Treatment Enabling Trial 2 (LATTE-2) phase 2b study, long-acting (LA) injectable cabotegravir + rilpivirine dosed every 8 weeks (Q8W) or every 4 weeks (Q4W) demonstrated comparable efficacy with daily oral antiretroviral therapy (ART) through 96 weeks in ART-naive adults with human immunodeficiency virus type 1 (HIV-1). Here we report efficacy, tolerability, and safety of cabotegravir + rilpivirine LA over approximately 5 years. Methods. After 20 weeks of oral cabotegravir + abacavir/lamivudine, participants were randomized to cabotegravir + rilpivirine LA Q8W or Q4W or continue oral ART through the 96-week maintenance period. In the extension period through week 256, participants continued their current LA regimen (randomized Q8W/Q4W groups) or switched from oral ART to Q8W or Q4W LA therapy (extension-switch groups). Endpoints assessed included proportion of participants with HIV-1 RNA 1 participant. Conclusions. Cabotegravir + rilpivirine LA exhibited long-term efficacy and tolerability, demonstrating its durability as maintenance therapy for HIV-1 infection.

Background The arrival of highly effective, well-tolerated, direct-acting antiviral agents (DAA) led to a dramatic decrease in hepatitis C virus (HCV) prevalence. Human immunodeficiency virus (HIV)-HCV–coinfected patients are deemed a priority population for HCV elimination, while a rise in recently acquired HCV infections in men who have sex with men (MSM) has been described. We describe the variations in HIV-HCV epidemiology in the French Dat’AIDS cohort. Methods This was a retrospective analysis of a prospective cohort of persons living with HIV (PLWH) from 2012 to 2018. We determined HCV prevalence, HCV incidence, proportion of viremic patients, treatment uptake, and mortality rate in the full cohort and by HIV risk factors. Results From 2012 to 2018, 50 861 PLWH with a known HCV status were followed up. During the period, HCV prevalence decreased from 15.4% to 13.5%. HCV prevalence among new HIV cases increased from 1.9% to 3.5% in MSM but remained stable in other groups. Recently acquired HCV incidence increased from 0.36/100 person-years to 1.25/100 person-years in MSM. The proportion of viremic patients decreased from 67.0% to 8.9%. MSM became the first group of viremic patients in 2018 (37.9%). Recently acquired hepatitis represented 59.2% of viremic MSM in 2018. DAA treatment uptake increased from 11.4% to 61.5%. More treatments were initiated in MSM in 2018 (41.2%) than in intravenous drug users (35.6%). In MSM, treatment at the acute phase represented 30.0% of treatments in 2018. Conclusions A major shift in HCV epidemiology was observed in PLWH in France from 2012 to 2018, leading to a unique situation in which the major group of HCV transmission in 2018 was MSM. Clinical Trials Registration. NCT02898987.

The dramatic recent advances and emergent trends in technologies have brought to the fore many vital and challenging questions and dilemmas for leaders and organizations. These are issues that call for a critical, insightful examination of key questions such as: are modern technologies beneficial or problematic for the well-being of individuals, organizations, and societies at large; why do we seem to feel more disconnected in an age of technological connectivity; can organizations reduce technology-induced stresses and find ways to enable the mindful use of technologies and how can organizations, governments and societies manage the use of technologies wisely? Such questions, when explored from various perspectives of wisdom, can yield significant insights, increase awareness of the issues, deepen the dialogue and help redesign an increasingly technology-driven future. However, there is little researched published material available on such questions and issues. Practical Wisdom in the Age of Technology: Insights, Issues and Questions for a New Millennium will provide a space to engage in thought-provoking dialogue and critical reflection on a variety of themes linking technology and practical wisdom. It will offer a foundation for exploration, inquiry, engagement, and discussion among organizational, political and social leaders, technology professionals, information systems academicians, wisdom researchers, managers, philosophers of technology, and other practitioners.

The impact of obesity on cardiovascular disease (CVD) outcomes in patients with type 2 diabetes mellitus (T2DM) and established coronary artery disease (CAD) is controversial; whether BMI and/or waist circumference correlate with atherothrombotic risk factors in such patients is uncertain. We sought to evaluate whether higher BMI or waist circumference are associated with specific risk factors among 2,273 Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) study participants with T2DM and documented CAD (baseline data, mean age 62 years, 66% non-Hispanic white, 71% men). Multiple linear regression models were constructed after adjusting for sex, age, race/ethnicity, US vs. non-US site, diabetes duration, exercise, smoking, alcohol, and relevant medication use. First-order partial correlations of BMI with risk factors after controlling for waist circumference and of waist circumference with risk factors after controlling for BMI were also evaluated. Ninety percent of the patients were overweight (BMI > or =25 kg/m(2)); 68% of men and 89% of women had high-risk waist circumference measures (> or =102 and > or =88 cm, respectively). BMI and waist circumference, in separate models, explained significant variation in metabolic (insulin, lipids, blood pressure (BP)) and inflammatory/procoagulation (C-reactive protein, PAI-1 activity and antigen, and fibrinogen) risk factors. In partial correlation analyses BMI was independently associated with BP and inflammatory/procoagulation factors, waist circumference with lipids, and both BMI and waist circumference with insulin. We conclude that, in cross-sectional analyses, both BMI and waist circumference, independently, are associated with increased atherothrombotic risk in centrally obese cohorts such as the BARI 2D patients with T2DM and CAD.

Previous studies of hepatic insulin gene therapy (HIGT) focused on glycemic effects of insulin produced from hepatocytes. In this study, we extend the observations of glycemic control with metabolically regulated HIGT to include systemic responses and whole-body metabolism. An insulin transgene was administered with an adenoviral vector [Ad/(GlRE)(3)BP1-2xfur] to livers of BB/Wor rats made diabetic with polyinosinic polycytidilic acid (poly-I:C) (HIGT group), and results compared with nondiabetic controls (non-DM), and diabetic rats receiving different doses of continuous-release insulin implants (DM-low BG and DM-high BG). Blood glucose and growth normalized in HIGT, with lower systemic insulin levels, elevated glucagon, and increased heat production compared with non-DM. Minimal regulation of systemic insulin levels were observed with HIGT, yet the animals maintained normal switching from carbohydrate to lipid metabolism determined by respiratory quotients (RQs), and tolerated 24-hour fasts without severe hypoglycemia. HIGT did not restore serum lipids as we observed increased triglycerides (TGs) and increased free fatty acids, but reduced weight of visceral fat pads despite normal total body fat content and retroperitoneal fat depots. HIGT favorably affects blood glucose, normalizes metabolic switching in diabetic rats, and reduces intra-abdominal fat deposition.

Background.Research has shown less aggressive treatment and poorer control of cardiovascular disease (CVD) risk factors in women than men.Methods.We analyzed sex differences in pharmacotherapy strategies and attainment of goals for hemoglobin A1c (HbA1c), blood pressure (BP), and low density lipoprotein cholesterol (LDL-C) in patients with type 2 diabetes and established coronary artery disease enrolled into the BARI 2D trial.Results.Similar numbers of drugs were prescribed in both women and men. Women were less frequent on metformin or sulfonylurea and more likely to take insulin and to be on higher doses of hydroxymethylglutaryl-CoA reductase inhibitors (statins) than men. After adjusting for baseline differences and treatment prescribed, women were less likely to achieve goals for HbA1c (OR = 0.71, 95% CI 0.57, 0.88) and LDL-C (OR = 0.64, 95% CI 0.53, 0.78). More antihypertensives were prescribed to women, and yet BP ≤ 130/80 mmHg did not differ by sex.Conclusions.Women entering the BARI 2D trial were as aggressively treated with drugs as men. Despite equivalent treatment, women less frequently met targets for HbA1c and LDL-C. Our findings suggest that there may be sex differences in response to drug therapies used to treat diabetes, hypertension, and hyperlipidemia.

A retrospective surveillance study was conducted to examine the micro-geographic variation of malaria incidence in three malaria-endemic communities in the Northern Peruvian Amazon. The annual malaria risk rate (per 100) ranged from 38% to 47% for Plasmodium vivax and from 15% to 18% for P. falciparum. Spatial clusters were found for P. vivax in Padre Cocha, Manacamiri, and Zungaro Cocha, and for P. falciparum only in Padre Cocha. Spatial-temporal clusters showed that the highest monthly number of P. vivax cases varied every year from December to March in 1996-1997 and from February to June in 1998-1999, and for P. falciparum from November to April in 1996-1997 and from January to April in 1998-1999. Our results suggest a constant presence of high-risk areas (hot spots) for malaria infection in periods with high or low malaria incidence. Modest targeted control efforts directed at identified high-risk areas may have significant impact on malaria transmission in this region.

We synthesized analogues of gp41 (553-590), 1, and evaluated them for their inhibitory activity against HIV-1 in MT4 cell assay (IC50(1) = 2.7 microM). (The numbering scheme for gp41 (e.g., gp41(553-590) for 1) adapted throughout the text is from ref 6.) Gradual truncation of either the N- or C-terminal end of gp41 (553-590) resulted in a substantial loss of inhibitory properties of resulting compounds. Unexpectedly, simultaneous truncations of both N- and C-termini of gp41(553-590) resulted in a potent heptadecamer, 13, IC50 = 10.4 microM. Coupling of a racemic alpha-aminotetradecanoic acid (Atd) to gp41 fragments afforded diastereomeric conjugates, most of which were chromatographically separable. In this series, pentadecamer 27 had an IC50 of 8.9 microM, while its Atd diastereomer 28 was much less inhibitory. This finding is consistent with relative inhibitory potencies of other Atd-containing diastereomeric pairs and could reflect a chiral sense of Atd residue interacting with the receptor. Compounds 13 and 27, which are practically equipotent to 1, represent minimalistic fragments of the leucine-zipper region of gp41 and constitute a basis for design of a second generation of gp41-based inhibitors. Circular dichroism studies suggested that compounds in this series are likely to inhibit HIV-1 replication by virtue of their alpha-helical character. The observed structure-activity relationship supports impairment of viral gp41 as a possible mechanism of action of 1.

This paper describes a new approach to an ecology practical in which 76 Level 4 students were divided into four groups (n = 20 +/-2) to collect data. Each group studied a different habitat and was further divided into seven subgroups (n = 2 or 3) to collect field data. Each of the four groups collaborated through Google Drive on descriptions and images of the habitat site, and also collaborated at the subgroup level on their own habitat data. The four groups then shared habitat descriptions with the aim to provide enough information to enable everyone to understand the entire data set. The three-stage assignment was assessed and feedback issued at group and individual level via the University’s online submission service (FASER), with some additional feedback given via Moodle, the University’s Virtual Learning Environment. Two separate submissions were made to FASER, the first was the group and subgroup work (stage 1), and the second included the peer assessment task (stage 2) and the individual evaluation of the habitats (stage 3). Feedback was given after the second submission had been uploaded to FASER and again when the assessment for the second submission was complete. The group and subgroup data sets were provided to all students via Moodle, so that individuals could carry out their own analysis of all four habitats. The use of Google Drive and Google Apps helped to improve the digital literacy of the staff and students involved. All three stages of the assignment were successful; over 85% of students passed the first two stages, and 82.9% passed stage 3. The collaborative work enabled students to produce high quality descriptive ecology documents valuable for the subsequent stages of the assignment. The peer assessment encouraged students to gain information on expected Undergraduate Minimum Standards, and gave students the opportunity to study multiple habitats. The final stage was open ended and challenged students to make sense of large ecological data sets. There was a positive correlation between levels of success at stages 1 and 3 for students who achieved less than 65% for the independent work, i.e. they benefited from carrying out group work. This collaborative, three-stage approach is recommended especially as it helps lower ability students gain subject knowledge and improve their presentation skills. However, some modifications are recommended: 1) simplifying the sample and data collection, and 2) providing more guidance for the peer assessment task and individual analysis. Learner autonomy enabled self-directed learning to take place and enriched large scale teaching as it encouraged student-student interaction. Significant differences between gender and ability are discussed.

A retrospective surveillance study was conducted to examine the micro-geographic variation of malaria incidence in three malaria-endemic communities in the Northern Peruvian Amazon. The annual malaria risk rate (per 100) ranged from 38% to 47% for Plasmodium vivax and from 15% to 18% for P. falciparum. Spatial clusters were found for P. vivax in Padre Cocha, Manacamiri, and Zungaro Cocha, and for P. falciparum only in Padre Cocha. Spatial-temporal clusters showed that the highest monthly number of P. vivax cases varied every year from December to March in 1996-1997 and from February to June in 1998-1999, and for P. falciparum from November to April in 1996-1997 and from January to April in 1998-1999. Our results suggest a constant presence of high-risk areas (hot spots) for malaria infection in periods with high or low malaria incidence. Modest targeted control efforts directed at identified high-risk areas may have significant impact on malaria transmission in this region.

Background Hepatic insulin gene therapy (HIGT) restores weight gain and near-normal glycemia in rodent models of insulin- deficient diabetes mellitus. However, the effect of transgenic insulin on endogenous genes and recipient cell function is relatively unexplored. To investigate hepatocellular effects of transgenic insulin expression, we evaluated intermediary glucose metabolism in primary cultured hepatocytes treated with HIGT. Methods Rat hepatocytes were transduced with adenovirus expressing a glucose-responsive human insulin transgene and cultured in high-glucose and high-insulin conditions. We determined glycogen content in cell cultures and intact liver directly. Glycogenolysis was compared using glucose production of cultured cells. Glucose uptake, oxidative, and glycolytic processing were determined by radiotracer analysis or direct end-product assessment. Quantitative real-time reverse transcriptase polymerase chain reaction was used to determine expression of glucose transporter 2 (GLUT2) and glucokinase genes. GLUT2 protein abundance was determined by Western blot analysis. Results HIGT-treated hepatocytes contained significantly less glycogen than either untreated hepatocytes or those treated with an empty virus. Glucose release owing to glycogenolysis remained normal. However, HIGT treatment significantly impaired glucose uptake and processing. Metabolic synthetic processes were not generally inhibited, as indicated by enhanced β-hydroxybutyrate secretion. While preserving cell viability, HIGT treatment diminished expression of both glucokinase and GLUT2. In HIGT-treated streptozocin-treated diabetic rats, total liver glycogen was intermediate between diabetic animals and normal controls. Conclusions These results suggest gene-specific effects in recipient hepatocytes following HIGT treatment and underscore the need for expanded studies examining host cell responses to the transfer of metabolically active transgenes.

Objective: To investigate the effects of mild to moderate caloric restriction on parameters of body growth, fat mass, and adipose tissue cellularity in female and male Wistar rats. Research Methods and Procedures: Three-month-old female and male Wistar rats were subjected to a chronic, mild to moderate caloric restriction paradigm (5%, 10%, or 20% reduction in caloric intake from ad libitum values) for 6 months. This was accomplished using a unique automated feeder system tailored to the food consumption levels of individual rats. Body weight and length, weight of lean organs, regional adipose mass, and adipose cellularity were measured before and after the diet restriction. Results: Caloric restriction produced proportional decelerations in body weight increases in both genders, without significant changes in body length or lean organ mass. Marked and disproportional reductions in regional adipose tissue mass were produced at all levels of food restriction (even at 5% restriction). An unexpected finding was that in response to graded caloric restriction, female rats preserved adipose fat cell number at the expense of fat cell volume, whereas the converse was seen for male rats. Discussion: These studies demonstrate a sexual dimorphism in the response to mild to moderate degrees of chronic caloric restriction. At low levels of caloric restriction, it is possible to affect regional adipose mass and cellularity while preserving lean organ mass.

Hepatic insulin gene therapy (HIGT) ameliorates hyperglycemia in multiple rodent models of diabetes mellitus, with variable degrees of glucose control. We demonstrate here that adenoviral delivery of a glucose-regulated transgene into rat hepatocytes produces near-normal glycemia in spontaneously diabetic BB/Wor rats without administration of exogenous insulin. We compared growth, glycemia, counterregulatory hormones, and lipids in HIGT-treated diabetic rats to nondiabetic rats and diabetic rats treated with either insulin injections or sustained-release insulin pellets. HIGT-treated rats achieved near-normal blood glucose levels within 1 week and maintained glycemic control for up to 3 months. Rats treated with sustained release insulin implants had similar blood sugars, but more hypoglycemia and gained more weight than HIGT-treated rats. HIGT-treated rats normalized blood glucose within 2 hr after a glucose load, and tolerated a 24-hr fast without hypoglycemia. HIGT treatment suppressed ketogenesis similarly to peripheral insulin. However, glucagon levels and free fatty acids were increased in HIGT-treated rats compared to either nondiabetic controls or rats treated with exogenous insulin. In addition to extending successful application of HIGT to a rat model of autoimmune diabetes, these findings emphasize the relative contribution of hepatic insulin effect in the metabolic stabilization of diabetes mellitus.

We hypothesized that exposure to tumor necrosis factor-alpha (TNF-alpha) would significantly increase lactate production by adipose-tissue (AT) fragments and isolated adipocytes. We therefore examined the effects of TNF-alpha on the metabolism of epididymal AT explants during 24-hour tissue incubation. We also studied the effects of this 24-hour TNF-alpha tissue exposure on subsequent glucose metabolism and lipolysis by isolated adipocytes. Glycerol release into the medium was significantly increased (50%, P =.027) by exposure of the AT fragments to TNF-alpha (4 nmol/L) for 24 hours. During this time, glucose uptake from the medium and lactate release into the medium tended to increase, whereas leptin release into the medium tended to decrease, but these effects of TNF-alpha were not statistically significant. After the 24-hour AT-explant incubation, adipocytes were isolated by means of collagenase digestion from the AT fragments and subsequently tested in a short-term (60-minute) metabolic incubation. Prior exposure to TNF-alpha resulted in a significant increase in adipocyte glycerol release (P =.044), total glucose metabolism (P =.019), and lactate production (P =.037). With the exception of lactate, TNF-alpha produced no significant stimulation of the metabolites of glucose. The pattern of glucose metabolism elicited by TNF-alpha exposure differs from that usually attributed to a lipolytic hormone and suggests that the effects of TNF-alpha on glucose metabolism involve pathways separate from, or in addition to, its effects on lipolytic stimulation.

Though not universally observed, moderately low-protein diets have been found to increase caloric intake and body fat. It appears that animals overeat in calories in order to obtain more dietary protein. For animals to control protein intake, they must be able to distinguish between two isocaloric diets containing different percentages of protein and make the appropriate dietary selection on the basis of their previous history of protein intake. Experiment 1 examined the 24-h diet selection (5 vs. 35% casein) of Sprague–Dawley rats that had been previously fed diets containing various percentages of dietary protein (5, 10, 20, 35, or 60% casein). Animals fed 5, 10, or 20% dietary protein showed a preference for the higher protein selection diet. In contrast, no significant diet preference was found in animals pre-fed the two higher levels of dietary protein (35 or 60% casein). In this study, daily food intake and body fat of rats fed the low-protein diets (5 and 10% casein) were similar to rats fed the 20% casein diet. Experiment 2 examined the effects of the level of methionine supplementation on rats fed 10% casein. In this study, food intake and body fat were increased by approximately 20% in rats fed 10% casein diets, regardless of the level of methionine supplementation (0.3 vs. 0.15%). Together, the results suggest that the presence of low-protein-induced hyperphagia helps maintain body protein levels in the face of moderately low dietary protein and promotes an increase in the amount of body fat and energy.

Cisplatin is an important antineoplastic agent. Its ototoxicity has been well defined, both in human and animal studies. However, animal models of systemic cisplatin administration have been complicated by multiple toxic effects. We studied cisplatin ototoxicity in an animal model involving topical application of cisplatin to the round-window membrane. Adult chinchillas were anesthetized with ketamine and pentobarbital, and auditory function was tested with the use of auditory brain-stem responses to various stimuli (clicks and 8-and 16-kHz tone bursts). Each animal was used as its own control. The middle-ear cavity was exposed through the bulla. In the experimental ear, a 25-microl solution of 0.25 mg cisplatin/1.0 ml normal saline solution was applied to the round-window membrane. In the control ear, 25 microl normal saline solution was applied to the round-window membrane. Follow-up auditory brain-stem response testing was conducted 7 days after treatment. A significant increase in threshold in the experimental ears was seen on comparison with the control ears. This finding suggests that application of cisplatin to the round-window membrane is a useful animal model in which to study cisplatin ototoxicity.

A series of experiments were conducted to determine whether the feeding of beef tallow compared with menhaden oil would affect renal cortex membrane composition, Na,K-ATPase activity, renal cholesterol uptake, and plasma lipoprotein cholesterol profile. BHE/cdb rats were used because they carry a genetic trait for non-insulin-dependent diabetes mellitus and are prone to develop diabetic nephropathy. Beef tallow feeding resulted in an increase in HDL cholesterol and an increase in Na,K-ATPase activity. The different fats also affected the arachidonic acid content of the membrane but not the membrane cholesterol content. These diet effects may explain why the development of renal disease in beef tallow-fed rats is delayed when compared with rats fed an equivalent amount of menhaden oil.

The old SPS RF control system designed in 1972 has been replaced completely, i.e. both hardware and software. The new system has to control both RF equipment conceived during the last 23 years and future (modern) equipment. Using information analysis methods, we derived a model of an RF command and designed a data base accordingly (ORACLE®). Information from this data base is used for command generation and processing and also for archiving settings. The advantage is purely generic software, i.e. the same computer code is used for switching on an RF amplifier, as for setting a frequency synthesizer. New equipment is added very simply by entering new records in the data base. Additional features include a reservation scheme whereby a user can take private control of any piece of equipment, a reporting facility notifying the user of the simultaneous control activity by other users on RF equipment, and a capability scheme assigning a level of expertise to each user restricting action on the equipment.

Sommaire du numéro :http://archive-edutice.ccsd.cnrs.fr/edutice-00000832; Le Lycée Saint-Sernin participant à l'expérience INRP sur l'introduction de la télédétection dois l'enseignement, nous avons eu l'occasion de nous initier à cette technique due le cadre des cours de sciences naturelles et de géographie. Nous avons continué en réalisant une étude d'"archéologie aérienne" sur la ville d'Evora (Portugal), par photo-interprétation. Les images satellites, à la résolution de plus en plus fine, permettent une étude nouvelle et diversifiée de la surface terrestre. Les nouveaux procédés mis en œuvre visent à adapter des traitements informatiques en vue d'une analyse la plus exhaustive possible des images, et ce quelque soit l'objectif visé. Pour notre part, disposant d'images simulées SPOT de Toulouse, nous nous sommes intéressés plus particulièrement à l'étude de la structure des rues. Il n'existe malheureusement pas de méthode universelle pour analyser des images numériques ; on est ainsi forcé d'adapter les traitements à l'image en fonction de l'objectif visé. Les principes de base de la télédétection ayant déjà été décrit dans l'article de Mme Estival, Mme Hirliman, M. Vauzelle : "Télédétection numérique et enseignement secondaire", Revue de l'EPI n° 38 p. 40 [edutice-00000974], nous insisterons sur les traitements spécifiques que nous avons développés.

3′-azido-3′-deoxythymidine (AZT) affected deoxynucleotide metabolism in the human cell lines, HL-60, H-9, K-562, and RPMI-8402. The respective ED 50 values of AZT for growth were 670, 110, 100, and 20 μM. When cells were exposed to 200 μM AZT, dTTP and dGTP decreased and dCTP increased. The increase in dCTP is in contrast to previous reports [Furman, et al., Proc. Nat. Acad. Sci. USA (1986) 83, 8333–8337]. Recovery of the dNTP pools was generally seen at 8 to 24 hrs. Pools of dCTP were the last to recover. Changes in the dNTP pools induced by AZT are consistant with a decline in dTTP affecting the allosteric regulation of ribonucleotide reductase. After 24 hrs in 200 μM AZT, AZT-5′-monophosphate reached 2800, 4700, 15700, and 12800 μM in the HL-60, H-9, K-562 and RPMI-8402 cells, respectively. The corresponding AZT-5′-triphosphate levels were 25, 15, 60, and 45 μM. Thymidine and deoxyuridine in the media increased after treatment of the cells with AZT. All cell lines treated with AZT secreted AZT-5′-monophosphate. Radiolabeled thymidine was used to study thymidine anabolism in cells treated with 20 μM AZT for 4 hrs. Pools of dTMP increased 3, 2, 4, and 7 fold in the respective cell lines. These data support the idea that thymidylate kinase is inhibited by AZT-5′-monophosphate (Furman et al., ibid) and suggest that cells in culture are able to overcome the effects of AZT on deoxynucleotide metabolism by expansion of their dTMP pool.

OBJECTIVE: Compliance with guidelines is increasingly used to benchmark the quality of hospital care, however, very little is known on patients admitted with acute coronary syndromes (ACS) and treated palliatively. This study aimed to evaluate the baseline characteristics and outcomes of these patients. DESIGN: Prospective cohort study. SETTING: Eighty-two Swiss hospitals enrolled patients from 1997 to 2014. PARTICIPANTS: All patients with ACS enrolled in the AMIS Plus registry (n=45,091) were analysed according to three treatment groups: palliative treatment, defined as use of aspirin and analgesics only and no reperfusion; conservative treatment, defined as any treatment including antithrombotics or anticoagulants, heparins, P2Y12 inhibitors, GPIIb/IIIa but no pharmacological or mechanical reperfusion; and reperfusion treatment (thrombolysis and/or percutaneous coronary intervention during initial hospitalisation). The primary outcome measure was in-hospital mortality and the secondary measure was 1-year mortality. RESULTS: Of the patients, 1485 (3.3%) were palliatively treated, 11,119 (24.7%) were conservatively treated and 32,487 (72.0%) underwent reperfusion therapy. In 1997, 6% of all patients were treated palliatively and this continuously decreased to 2% in 2013. Baseline characteristics of palliative patients differed in comparison with conservatively treated and reperfusion patients in age, gender and comorbidities (all p

To assess the impact of admission to different hospital types on early and 1-year outcomes in patients with acute coronary syndrome (ACS). Between 1997 and 2009, 31 010 ACS patients from 76 Swiss hospitals were enrolled in the AMIS Plus registry. Large tertiary institutions with continuous (24 hour/7 day) cardiac catheterisation facilities were classified as type A hospitals, and all others as type B. For 1-year outcomes, a subgroup of patients admitted after 2005 were studied. Eleven type A hospitals admitted 15987 (52%) patients and 65 type B hospitals 15023 (48%) patients. Patients admitted into B hospitals were older, more frequently female, diabetic, hypertensive, had more severe comorbidities and more frequent non-ST segment elevation (NSTE)-ACS/unstable angina (UA). STE-ACS patients admitted into B hospitals received more thrombolysis, but less percutaneous coronary intervention (PCI). Crude in-hospital mortality and major adverse cardiac events (MACE) were higher in patients from B hospitals. Crude 1-year mortality of 3747 ACS patients followed up was higher in patients admitted into B hospitals, but no differences were found for MACE. After adjustment for age, risk factors, type of ACS and comorbidities, hospital type was not an independent predictor of in-hospital mortality, in-hospital MACE, 1-year MACE or mortality. Admission indicated a crude outcome in favour of hospitalisation during duty-hours while 1-year outcome could not document a significant effect. ACS patients admitted to smaller regional Swiss hospitals were older, had more severe comorbidities, more NSTE-ACS and received less intensive treatment compared with the patients initially admitted to large tertiary institutions. However, hospital type was not an independent predictor of early and mid-term outcomes in these patients. Furthermore, our data suggest that Swiss hospitals have been functioning as an efficient network for the past 12 years.