The Poverty Culture Huret, Romain D
The Experts' War on Poverty,
10/2018
Book Chapter
In the 1950s, federal research investigating the low-income and disadvantaged segments of society remained invisible. A cultural and psychological view of poverty, however, tended to dominate public ...discourse. The poverty paradox was explained by individual choices and specific behaviors. Why so many communities, populated largely by racial and ethnic minorities, remained so poor in the midst of increasing wealth became the subject of intense debate. Poverty was still largely considered to be the result of individual shortcomings as opposed to structural or monetary factors. Racial bias strongly reinforced such a vision, which alleged that there was no paradox at all,
The crystallographic phase problem is routinely solved when imaging small molecules but remains a key component and difficult step in protein crystallography. Current phasing approaches are either ...experimentally based or rely on the knowledge of an homologous structure. With the recent advances in phasing algorithms called iterative projections algorithms (IPAs), ab initio phasing methods, where only minimal extra information is needed are gaining interest in protein crystallography, as they potentially offer a dramatic reduction in effort over experimental methods and are not affected by model bias. Two versions of a new ab initio phase retrieval method are presented in this paper. These rely on the measurement of the diffraction from two or more crystal forms of the same molecule. The required IPA constraint projections are derived and 2D simulations using the difference map algorithm to illustrate the convergence properties of the methods in presence of object overlap. A 3D simulation illustrates potential use and effectiveness of the algorithm.
Summary Background Monochorionic twin pregnancies complicated by twin-to-twin transfusion syndrome are typically treated with fetoscopic laser coagulation. Postoperative complications can occur due ...to residual vascular anastomoses on the placenta. We aimed to assess the efficacy and safety of a novel surgery technique that uses laser coagulation of the entire vascular equator (Solomon technique). Methods We undertook an open-label, international, multicentre, randomised controlled trial at five European tertiary referral centres. Women with twin-to-twin transfusion syndrome were randomly assigned by online randomisation (1:1) with permuted blocks to the Solomon technique or standard laser coagulation. The primary outcome was a composite of incidence of twin anaemia polycythaemia sequence, recurrence of twin-to-twin transfusion syndrome, perinatal mortality, or severe neonatal morbidity. Analyses were by intention to treat, with results expressed as odds ratios (ORs) and 95% CIs. This trial is registered with the Dutch Trial Registry, number NTR1245. Findings Between March 11, 2008, and July 12, 2012, 274 women were randomly assigned to either the Solomon group (n=139) or the standard treatment group (n=135). The primary outcome occurred in 94 (34%) of 274 fetuses in the Solomon group versus 133 (49%) of 270 in the standard treatment group (OR 0·54; 95% CI 0·35–0·82). The Solomon technique was associated with a reduction in twin anaemia polycythaemia sequence (3% vs 16% for the standard treatment; OR 0·16, 95% CI 0·05–0·49) and recurrence of twin-to-twin transfusion syndrome (1% vs 7%; 0·21, 0·04–0·98). Perinatal mortality and severe neonatal morbidity did not differ significantly between the two groups. Outside of the common and well-known complications of twin-to-twin transfusion syndrome and its treatment, no serious adverse events occurred. Interpretation Fetoscopic laser coagulation of the entire vascular equator reduces postoperative fetal morbidity in severe twin-to-twin transfusion syndrome. We recommend that fetoscopic surgeons consider adopting this strategy for treatment of women with twin-to-twin transfusion syndrome. Funding Netherlands Organization for the Health Research and Development (ZonMw 92003545).
AbstractObjectiveFailure of thoracic endovascular aortic repair (TEVAR) in chronic aortic dissections can be partially explained by retrograde false lumen (FL) flow through distal re-entry tears. ...After implantation of a thoracic stent graft, FL thrombosis occurs in less than 50% of the cases. The objectives of this study were to describe the feasibility and outcomes of FL embolization in patients with chronic aortic dissections. MethodsBetween June 2015 and January 2018, 27 patients (mean age, 61 ± 14 years) with chronic aortic dissection underwent FL embolization as an adjunct during or after TEVAR placement procedure. Indications for embolization were (1) symptomatic chronic aortic dissections with pain or rapid growth of aortic diameter (≥5 mm/y) requiring rapid exclusion of the aneurysm, (2) aneurysmal dilatation with persistent FL retrograde flow after TEVAR, and (3) large FL aneurysms (≥55 mm) that might lead to persistent retrograde flow. Twenty patients presented with type B chronic aortic dissections (74.1%) and seven presented a residual type A chronic aortic dissections (25.9%). Eight patients had a previous aortic arch replacement (29.6%). Six patients had previous repair with TEVAR (22.2%). The delay between the onset of dissection and the first endovascular repair was 47 months (range, 3-144). Spinal fluid drainage was used in 74.1% of cases (20/27 patients). Embolization devices included coils and vascular plugs. ResultsThe technical success rate was 100% (27/27). Complete spinal cord ischemia was observed in one patient (3.7%). There was one hospital death from pneumonia after zone 1 supra-aortic trunk debranching with TEVAR and embolization. After the index procedure, FL thrombosis was observed in 81.5% of patients (22/27) on late phase computed tomography angiography. Five patients required two or more embolization procedures, leading to a high rate of complete FL thrombosis (92.6%). One patient presented a type IB endoleak and one patient presented a type II endoleak. Radiologic follow-up was 20 ± 10 months. The maximum thoracic aortic diameter significantly decreased from 63 mm to 54 ± 10 mm ( P < .001). ConclusionsEmbolization of the FL of chronic aortic dissections is technically feasible with a low morbidity rate. The FL thrombosis is observed in the majority of case and promotes favorable thoracic aortic remodeling. Longer follow-up is needed to confirm these good results on the thoracic aorta and this technique may, therefore, improve the results of TEVAR in chronic aortic dissections.
Background Invasive infections of the central nervous system (CNS) or digestive tract caused by commensal fungi of the genus Candida are rare and life-threatening. The known risk factors include ...acquired and inherited immunodeficiencies, with patients often displaying a history of multiple infections. Cases of meningoencephalitis, colitis, or both caused by Candida species remain unexplained. Objective We studied 5 previously healthy children and adults with unexplained invasive disease of the CNS, digestive tract, or both caused by Candida species. The patients were aged 39, 7, 17, 37, and 26 years at the time of infection and were unrelated, but each was born to consanguineous parents of Turkish (2 patients), Iranian, Moroccan, or Pakistani origin. Meningoencephalitis was reported in 3 patients, meningoencephalitis associated with colitis was reported in a fourth patient, and the fifth patient had colitis only. Methods Inherited caspase recruitment domain family, member 9 (CARD9) deficiency was recently reported in otherwise healthy patients with other forms of severe disease caused by Candida , Trichophyton , Phialophora , and Exophiala species, including meningoencephalitis but not colitis caused by Candida and Exophiala species. Therefore we sequenced CARD9 in the 5 patients. Results All patients were found to be homozygous for rare and deleterious mutant CARD9 alleles: R70W and Q289* for the 3 patients with Candida albicans –induced meningoencephalitis, R35Q for the patient with meningoencephalitis and colitis caused by Candida glabrata , and Q295* for the patient with Candida albicans –induced colitis. Regardless of their levels of mutant CARD9 protein, the patients' monocyte-derived dendritic cells responded poorly to CARD9-dependent fungal agonists (curdlan, heat-killed C albicans , Saccharomyces cerevisiae , and Exophiala dermatitidis ). Conclusion Invasive infections of the CNS or digestive tract caused by Candida species in previously healthy children and even adults might be caused by inherited CARD9 deficiency.
Combinations of topoisomerase I (topo I) poisons and platinum derivatives have synergistic antitumoral effects. However, their clinical development is limited by supra-additive haematological ...toxicity. The aim of this study was to determine whether sustained doses of topotecan and oxaliplatin could be achieved using a synergistic sequence. 34 advanced cancer patients and 186 cycles were evaluable for toxicity over five dosing levels. Oxaliplatin at 85–110 mg/m
2 was given on day 1, followed by topotecan 0.5–1.25 mg/m
2/day×5 from day 1 to 5, every 3 weeks. Plasma pharmacokinetics (PK) of total and ultrafiltrable platinum, total and lactone forms of topotecan were determined in the first cycle. The dose-limiting toxicity (DT) was identified as grade 4 thrombocytopenia. The occurrence of grade 4 thrombocytopenia did not correlate with topotecan PK, but it did with the patient's characteristics. Severe thrombocytopenia was seen in 1/8 of patients without clinical or biological evidence of malnutrition, with a creatinine clearance higher than 1 ml/s, and no more than two previous chemotherapy regimens, while it was seen in 8/10 patients with one of these characteristics (
P<0.004). In conclusion, the recommended doses of oxaliplatin 110 mg/m
2 and topotecan 1 mg/m
2/day, every 3 weeks can be administered to patients with a favourable general status and pretreatment characteristics and a phase II study is worthwhile in ovarian cancer patients.
Summary Background Erlotinib has been shown to improve progression-free survival compared with chemotherapy when given as first-line treatment for Asian patients with non-small-cell lung cancer ...(NSCLC) with activating EGFR mutations. We aimed to assess the safety and efficacy of erlotinib compared with standard chemotherapy for first-line treatment of European patients with advanced EGFR-mutation positive NSCLC. Methods We undertook the open-label, randomised phase 3 EURTAC trial at 42 hospitals in France, Italy, and Spain. Eligible participants were adults (>18 years) with NSCLC and EGFR mutations (exon 19 deletion or L858R mutation in exon 21) with no history of chemotherapy for metastatic disease (neoadjuvant or adjuvant chemotherapy ending ≥6 months before study entry was allowed). We randomly allocated participants (1:1) according to a computer-generated allocation schedule to receive oral erlotinib 150 mg per day or 3 week cycles of standard intravenous chemotherapy of cisplatin 75 mg/m2 on day 1 plus docetaxel (75 mg/m2 on day 1) or gemcitabine (1250 mg/m2 on days 1 and 8). Carboplatin (AUC 6 with docetaxel 75 mg/m2 or AUC 5 with gemcitabine 1000 mg/m2 ) was allowed in patients unable to have cisplatin. Patients were stratified by EGFR mutation type and Eastern Cooperative Oncology Group performance status (0 vs 1 vs 2). The primary endpoint was progression-free survival (PFS) in the intention-to-treat population. We assessed safety in all patients who received study drug (≥1 dose). This study is registered with ClinicalTrials.gov , number NCT00446225. Findings Between Feb 15, 2007, and Jan 4, 2011, 174 patients with EGFR mutations were enrolled. One patient received treatment before randomisation and was thus withdrawn from the study; of the remaining patients, 86 were randomly assigned to receive erlotinib and 87 to receive standard chemotherapy. The preplanned interim analysis showed that the study met its primary endpoint; enrolment was halted, and full evaluation of the results was recommended. At data cutoff (Jan 26, 2011), median PFS was 9·7 months (95% CI 8·4-12·3) in the erlotinib group, compared with 5·2 months (4·5–5·8) in the standard chemotherapy group (hazard ratio 0·37, 95% CI 0·25–0·54; p<0·0001). Main grade 3 or 4 toxicities were rash (11 13% of 84 patients given erlotinib vs none of 82 patients in the chemotherapy group), neutropenia (none vs 18 22%), anaemia (one 1% vs three 4%), and increased amino-transferase concentrations (two 2% vs 0). Five (6%) patients on erlotinib had treatment-related severe adverse events compared with 16 patients (20%) on chemotherapy. One patient in the erlotinib group and two in the standard chemotherapy group died from treatment-related causes. Interpretation Our findings strengthen the rationale for routine baseline tissue-based assessment of EGFR mutations in patients with NSCLC and for treatment of mutation-positive patients with EGFR tyrosine-kinase inhibitors. Funding Spanish Lung Cancer Group, Roche Farma, Hoffmann-La Roche, and Red Temática de Investigacion Cooperativa en Cancer.
Biventricular pacing (BVP) may not achieve complete electrical resynchronization.
The purpose of this study was to assess whether the resynchronizing effect of BVP varies among patients depending on ...the underlying electrical substrate.
High-resolution electrocardiographic mapping with invasive measurement of the maximal rate of systolic left ventricular (LV) pressure rise (LVdP/dtmax) was performed during baseline activation and during BVP in 61 patients with heart failure with various conduction delays: 13 with narrow QRS duration (<120 ms), 22 with nonspecific intraventricular conduction disturbance, and 26 with left bundle branch block. Electrical dyssynchrony, both during baseline activation and BVP, was quantified by total and LV activation times (TAT and LVTAT) and by ventricular electrical uncoupling (VEU = mean LVTAT - mean right ventricular activation time). Response to BVP was defined as a ≥10% increase in LVdP/dtmax.
The electrical activation pattern during BVP was similar for all patient groups and, hence, not dependent on baseline conduction disturbance. During BVP, TAT, LVTAT, and VEU were similar for all groups and were either not correlated or weakly correlated with the change in LVdP/dtmax. In contrast, changes in electrical dyssynchrony correlated significantly with the change in LVdP/dtmax: r=0.71, 0.69, and 0.69 for ∆TAT, ∆LVTAT, and ∆VEU, respectively (all P < .001). Responders showed higher baseline dyssynchrony levels and BVP-induced dyssynchrony reduction than did nonresponders (all P < .001); in nonresponders, BVP worsened activation times than did baseline activation.
BVP does not eliminate electrical dyssynchrony, but rather brings it to a common level independent of the patient's underlying electrical substrate. Therefore, BVP is of benefit to patients with dyssynchrony but not to patients with insufficient electrical dyssynchrony in whom it induces an iatrogenic electropathy.
Bloom syndrome (BS) is an autosomal recessive disorder characterized by increases in the frequency of sister-chromatid exchange and in the incidence of malignancy. Chromosome-transfer studies have ...shown the BS locus to map to chromosome 15q. This report describes a subject with features of both BS and Prader-Willi syndrome (PWS). Molecular analysis showed maternal uniparental disomy for chromosome 15. Meiotic recombination between the two disomic chromosomes 15 has resulted in heterodisomy for proximal 15q and isodisomy for distal 15q. In this individual BS is probably due to homozygosity for a gene that is telomeric to D15S95 (15q25), rather than to genetic imprinting, the mechanism responsible for the development of PWS. This report represents the first application of disomy analysis to the regional localization of a disease gene. This strategy promises to be useful in the genetic mapping of other uncommon autosomal recessive conditions.
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