Joseph Moxon: Fueled by Science, Extinguished by Class. How a Forgotten Middle-Classed Early Modern English Puritan Printer Mathematician and Globe-Maker Helped Forge the Scientific Revolution and Democratize Knowledge Among the Trades

Joseph Moxon, raised within the trades, elevated into the middle-class, was an inducted Fellow of the Royal Society, Hydrographer to the King’s Most Excellent Majesty, Printer, Author, Translator, Maker of Globes and of Spheres, Maker of Maps and of Mathematical Instruments, Engraver, and Entrepreneur. Moxon was the quintessential Renaissance Man. A tradesman living in a time of great scientific intrigue and discovery, Moxon, acknowledged by few mid-seventeenth century historians, rightfully contributed his scientific discoveries—in the forms of tutorials and manuals written for the common man—as a testimony to all printers who have helped in the progression of the Scientific Revolution. For without them, books would not have been printed, knowledge would not have been shared, and innovation and discovery would have been possibly retarded and/or stifled. This paper presents his story through the acclaimed yet forgotten works of Moxon’s Mechanick Exercises Volume I and Volume II as the first scientifically influenced instructional manuals and guides for the trades and as the foundation for acknowledging the printing press as the catalyst for democratizing knowledge

Clinical Determinants and Prognostic Implications of Renin and Aldosterone in Patients with Symptomatic Heart Failure

Aims Activation of the renin-angiotensin-aldosterone system plays an important role in the pathophysiology of heart failure (HF) and has been associated with poor prognosis. There are limited data on the associations of renin and aldosterone levels with clinical profiles, treatment response, and study outcomes in patients with HF. Methods and results We analysed 2,039 patients with available baseline renin and aldosterone levels in BIOSTAT-CHF (a systems BIOlogy study to Tailored Treatment in Chronic Heart Failure). The primary outcome was the composite of all-cause mortality or HF hospitalization. We also investigated changes in renin and aldosterone levels after administration of mineralocorticoid receptor antagonists (MRAs) in a subset of the EPHESUS trial and in an acute HF cohort (PORTO). In BIOSTAT-CHF study, median renin and aldosterone levels were 85.3 (percentile(25-75) = 28-247) mu IU/mL and 9.4 (percentile(25-75) = 4.4-19.8) ng/dL, respectively. Prior HF admission, lower blood pressure, sodium, poorer renal function, and MRA treatment were associated with higher renin and aldosterone. Higher renin was associated with an increased rate of the primary outcome [highest vs. lowest renin tertile: adjusted-HR (95% CI) = 1.47 (1.16-1.86), P = 0.002], whereas higher aldosterone was not [highest vs. lowest aldosterone tertile: adjusted-HR (95% CI) = 1.16 (0.93-1.44), P = 0.19]. Renin and/or aldosterone did not improve the BIOSTAT-CHF prognostic models. The rise in aldosterone with the use of MRAs was observed in EPHESUS and PORTO studies. Conclusions Circulating levels of renin and aldosterone were associated with both the disease severity and use of MRAs. By reflecting both the disease and its treatments, the prognostic discrimination of these biomarkers was poor. Our data suggest that the "point" measurement of renin and aldosterone in HF is of limited clinical utility

Selecting HIV infection prevention interventions in the mature HIV epidemic in Malawi using the mode of transmission model

<p>Abstract</p> <p>Background</p> <p>Malawi is reassessing its HIV prevention strategy in the light of a limited reduction in the epidemic. No community based incidence studies have been carried out in Malawi, so estimates of where new infections are occurring require the use of mathematical models and knowledge of the size and sexual behaviour of different groups. The results can help to choose where HIV prevention interventions are most needed.</p> <p>Methods</p> <p>The UNAIDS Mode of Transmission model was populated with Malawi data and estimates of incident cases calculated for each exposure group. Scenarios of single and multiple interventions of varying success were used to identify those interventions most likely to reduce incident cases.</p> <p>Results</p> <p>The groups accounting for most new infections were the low-risk heterosexual group - the discordant couples (37%) and those who had casual sex and their partners (a further 16% and 27% respectively) of new cases.</p> <p>Circumcision, condoms with casual sex and bar girls and improved STI treatment had limited effect in reducing incident cases, while condom use with discordant couples, abstinence and a zero-grazing campaign had major effects. The combination of a successful strategy to eliminate multiple concurrent partners and a successful strategy to eliminate all infections between discordant couples would reduce incident cases by 99%.</p> <p>Conclusions</p> <p>A revitalised HIV prevention strategy will need to include interventions which tackle the two modes of transmission now found to be so important in Malawi - <b>concurrency and discordancy</b>.</p

Lipid-Based Nutrient Supplements Increase Energy and Macronutrient Intakes from Complementary Food among Malawian Infants.

BACKGROUND: Low intakes of good-quality complementary foods (CFs) contribute to undernutrition and consequently negatively affect health, growth, and development. Lipid-based nutrient supplements (LNSs) are designed to ensure dietary adequacy in micronutrients and essential fatty acids and to provide some energy and high-quality protein. In populations in which acute energy deficiency is rare, the dose-dependent effect of LNSs on CF intakes is unknown. OBJECTIVE: The objective of this study was to evaluate the difference in energy and macronutrient intakes from CF between a control (no supplement) group and 3 groups that received 10, 20, or 40 g LNS/d. METHODS: We collected repeated interactive 24-h dietary recalls from caregivers of rural Malawian 9- to 10-mo-old infants (n = 748) to estimate dietary intakes (LNS and all non-breast-milk foods) of energy and macronutrients and their dietary patterns. All infants were participating in a 12-mo randomized controlled trial to investigate the efficacy of various doses of LNS for preventing undernutrition. RESULTS: Dietary energy intakes were significantly higher among infants in the LNS intervention groups than in the control group (396, 406, and 388 kcal/d in the 10-, 20-, and 40-g LNS/d groups, respectively, compared with 345 kcal/d; each pairwise P < 0.05), but no significant differences were found in energy intakes between groups who were administered the different LNS doses (10 g LNS/d compared with 20 g LNS/d: P = 0.72; 10 g LNS/d compared with 40 g LNS/d: P ≥ 0.67; 20 g LNS/d compared with 40 g LNS/d: P = 0.94). Intakes of protein and fat were significantly higher in the LNS intervention groups than in the control group. No significant intergroup differences were found in median intakes of energy from non-LNS CFs (357, 347, and 296 kcal/d in the 10-, 20-, and 40-g LNS/d groups, respectively, compared with 345 kcal/d in the control group; P = 0.11). CONCLUSION: LNSs in doses of 10-40 g/d increase intakes of energy and macronutrients among 9- to 10-mo-old Malawian infants, without displacing locally available CFs. This trial was registered at clinicaltrials.gov as NCT00945698

Polar firn properties in Greenland and Antarctica and related effects on microwave brightness temperatures

In studying the mass balance of polar ice sheets, fluctuations in firn density near the surface is a major uncertainty. In this paper, we explore these variations at locations on the Greenland Ice Sheet and at the Dome C location in Antarctica. Borehole in situ measurements, snow radar echoes, microwave brightness temperatures, and modeling results from the Community Firn Model (CFM) are used. It is shown that firn density profiles can be represented using three processes: "long-scale"and "short-scale"density variations and "refrozen layers". Consistency with this description is observed in the dynamic range of airborne 0.5-2GHz brightness temperatures and snow radar echo peaks in measurements performed in Greenland in 2017. Based on these insights, a new analytical partially coherent model is implemented to explain the microwave brightness temperatures using the three-scale description of the firn. Short- and long-scale firn processes are modeled as a 3D continuous random medium with finite vertical and horizontal correlation lengths as opposed to past 1D randomly layered medium descriptions. Refrozen layers are described as deterministic sheets with planar interfaces, with the number of refrozen-layer interfaces determined by radar observations. Firn density and correlation length parameters used in forward modeling to match measured 0.5-2GHz brightness temperatures in Greenland show consistency with similar parameters in CFM predictions. Model predictions also are in good agreement with multi-angle 1.4GHz vertically and horizontally polarized brightness temperature measured by the Soil Moisture and Ocean Salinity (SMOS) satellite at Dome C, Antarctica. This work shows that co-located active and passive microwave measurements can be used to infer polar firn properties that can be compared with predictions of the CFM. In particular, 0.5-2GHz brightness temperature measurements are shown to be sensitive to long-scale firn density fluctuations with density standard deviations in the range of 0.01-0.06gcm-3 and vertical correlation lengths of 6-20cm

Heart failure etiologies and clinical factors precipitating for worsening heart failure: Findings from BIOSTAT-CHF

Background: Knowledge on the association between heart failure (HF) etiologies, precipitant causes and clinical outcomes may help in ascertaining patient's risk and in selecting tailored therapeutic strategies. Methods: The prognostic value of both HF etiologies and precipitants for worsening HF were analyzed using the index cohort of BIOSTAT-CHF. The studied HF etiologies were: a) ischemic HF; b) dilated cardiomyopathy; c) hypertensive HF; d) valvular HF; and e) other/unknown. The precipitating factors for worsening HF were: a) atrial fibrillation; b) non-adherence; c) renal failure; d) acute coronary syndrome; e) hypertension; and f) Infection. The primary outcome was the composite of all-cause death or HF hospitalization. Results: Among 2465 patients included in the study, 45% (N = =1102) had ischemic HF, 23% (N = =563) dilated cardiomyopathy, 15% (N = =379) other/unknown, 10% (N = =237) hypertensive and 7% (N = =184) valvular HF. Patients with ischemic HF had the worst prognosis, whereas patients with dilated cardiomyopathy had the best prognosis. From the precipitating factors for worsening HF, renal failure was the one independently associated with worse prognosis (adjusted HR (95%CI) = =1.48 (1.04–2.09), p 0.10 for all). Treatment up-titration benefited patients regardless of their underlying etiology or precipitating cause (p interaction > 0.10 for all). Conclusions: In BIOSTAT-CHF, patients with HF of an ischemic etiology, and those with worsening HF precipitated by renal failure (irrespective of the underlying HF etiology), had the highest rates of death and HF hospitalization, but still benefited equally from treatment up-titration

Lenalidomide, bortezomib, and dexamethasone with transplantation for myeloma

BACKGROUND High-dose chemotherapy plus autologous stem-cell transplantation has been the standard treatment for newly diagnosed multiple myeloma in adults up to 65 years of age. However, promising data on the use of combination therapy with lenalidomide, bortezomib, and dexamethasone (RVD) in this population have raised questions about the role and timing of transplantation. METHODS We randomly assigned 700 patients with multiple myeloma to receive induction therapy with three cycles of RVD and then consolidation therapy with either five additional cycles of RVD (350 patients) or high-dose melphalan plus stem-cell transplantation followed by two additional cycles of RVD (350 patients). Patients in both groups received maintenance therapy with lenalidomide for 1 year. The primary end point was progression-free survival. RESULTS Median progression-free survival was significantly longer in the group that underwent transplantation than in the group that received RVD alone (50 months vs. 36 months; adjusted hazard ratio for disease progression or death, 0.65; P<0.001). This benefit was observed across all patient subgroups, including those stratified according to International Staging System stage and cytogenetic risk. The percentage of patients with a complete response was higher in the transplantation group than in the RVD-Alone group (59% vs. 48%, P = 0.03), as was the percentage of patients in whom minimal residual disease was not detected (79% vs. 65%, P<0.001). Overall survival at 4 years did not differ significantly between the transplantation group and the RVD-Alone group (81% and 82%, respectively). The rate of grade 3 or 4 neutropenia was significantly higher in the transplantation group than in the RVD-Alone group (92% vs. 47%), as were the rates of grade 3 or 4 gastrointestinal disorders (28% vs. 7%) and infections (20% vs. 9%). No significant between-group differences were observed in the rates of treatmentrelated deaths, second primary cancers, thromboembolic events, and peripheral neuropathy. CONCLUSIONS Among adults with multiple myeloma, RVD therapy plus transplantation was associated with significantly longer progression-free survival than RVD therapy alone, but overall survival did not differ significantly between the two approaches. (Supported by Celgene and others; IFM 2009 Study ClinicalTrials.gov number, NCT01191060.).SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Evaluation of Minimal Residual Disease (MRD) By Next Generation Sequencing (NGS) Is Highly Predictive of Progression Free Survival in the IFM/DFCI 2009 Trial

International audience57th Annual Meeting of the American-Society-of-Hematology Location: Orlando, FL Date: DEC 05-08, 201