AIDS and New England Hospitals

The Centers for Disease Control projects that nine thousand persons with AIDS will be alive in New England in 1991, representing a sevenfold increase from 1986. Our analysis indicates that more than 2 percent of medical/surgical beds in New England will be used for AIDS care by 1991, representing 766 fully occupied hospital beds. The direct cost of providing hospital care to New England\u27s AIDS patients is projected to be $195.2 million in 1991, reflecting 3 percent of all hospital inpatient costs in the region. AIDS treatment is very unevenly distributed among hospitals in New England. Just twenty hospitals (8 percent of short-term general hospitals in the region) provided over 60 percent of the care required by all AIDS patients in New England in 1986. If this trend continues, nearly 5 percent of all the beds available in these twenty institutions will be required for AIDS care by 1991. Alternatives to inpatient care are an important means of limiting the demands the AIDS epidemic places on inpatient care facilities. A number of outpatient AIDS clinics have been established in New England hospitals, including clinics at Yale-New Haven Hospital and Rhode Island Hospital. However, skilled nursing facilities in New England, as in other parts of the country, are not prepared to care for AIDS patients. Similarly, the development of in-home services for AIDS patients is just beginning in New England. Hospital planning for New England should begin addressing the need to expand alternative care services. Hospitals may begin by developing an integrated system of inpatient care with outpatient clinics and by designing units or multidisciplinary teams to care for AIDS patients. But even the best case management and discharge planning efforts cannot succeed if there is no place outside the hospital for AIDS patients to go. Each state needs to look closely at its capacity to provide long-term care, hospice care, and home care in order to fill gaps where they exist

Common breast cancer susceptibility alleles are associated with tumor subtypes in BRCA1 and BRCA2 mutation carriers : results from the Consortium of Investigators of Modifiers of BRCA1/2.

Abstract Introduction Previous studies have demonstrated that common breast cancer susceptibility alleles are differentially associated with breast cancer risk for BRCA1 and/or BRCA2 mutation carriers. It is currently unknown how these alleles are associated with different breast cancer subtypes in BRCA1 and BRCA2 mutation carriers defined by estrogen (ER) or progesterone receptor (PR) status of the tumour. Methods We used genotype data on up to 11,421 BRCA1 and 7,080 BRCA2 carriers, of whom 4,310 had been affected with breast cancer and had information on either ER or PR status of the tumour, to assess the associations of 12 loci with breast cancer tumour characteristics. Associations were evaluated using a retrospective cohort approach. Results The results suggested stronger associations with ER-positive breast cancer than ER-negative for 11 loci in both BRCA1 and BRCA2 carriers. Among BRCA1 carriers, single nucleotide polymorphism (SNP) rs2981582 (FGFR2) exhibited the biggest difference based on ER status (per-allele hazard ratio (HR) for ER-positive = 1.35, 95% CI: 1.17 to 1.56 vs HR = 0.91, 95% CI: 0.85 to 0.98 for ER-negative, P-heterogeneity = 6.5 × 10-6). In contrast, SNP rs2046210 at 6q25.1 near ESR1 was primarily associated with ER-negative breast cancer risk for both BRCA1 and BRCA2 carriers. In BRCA2 carriers, SNPs in FGFR2, TOX3, LSP1, SLC4A7/NEK10, 5p12, 2q35, and 1p11.2 were significantly associated with ER-positive but not ER-negative disease. Similar results were observed when differentiating breast cancer cases by PR status. Conclusions The associations of the 12 SNPs with risk for BRCA1 and BRCA2 carriers differ by ER-positive or ER-negative breast cancer status. The apparent differences in SNP associations between BRCA1 and BRCA2 carriers, and non-carriers, may be explicable by differences in the prevalence of tumour subtypes. As more risk modifying variants are identified, incorporating these associations into breast cancer subtype-specific risk models may improve clinical management for mutation carriers

A first update on mapping the human genetic architecture of COVID-19

peer reviewe

Le groupe d'études politiques « Reconstruction » et la C.E.D

Singer Madeleine. Le groupe d'études politiques « Reconstruction » et la C.E.D. In: Revue d’histoire moderne et contemporaine, tome 43 N°1, Janvier-mars 1996. La vie politique en France, hommes et débats, 1930-1960. pp. 35-66

Paul Vignaux, intellectuel et syndicaliste, devant la guerre d'Algérie

Singer Madeleine. Paul Vignaux, intellectuel et syndicaliste, devant la guerre d'Algérie. In: Les Cahiers de l'Institut d'Histoire du Temps Présent, n°10, novembre 1988. La guerre d’Algérie et les intellectuels français. pp. 167-179

Aux origines de la C.F.T.C., à Halluin : le Sillon et la Jeune République

Léon Saint-Venant and Madeleine Singer, At the C.F.T.C.'s origins in Halluin : the Sillon and the Jeune République. The Christian militants of Halluin take part as early as 1902 in the Sillon movement initiated by Marc Sangnier. Two years later, one of them organizes a "worker's union of the Halluin textile industry" which will be represented at the C.F.T.C.'s constitutive congress in 1919. Many of these militants take part in the meetings and departmental congresses of the Jeune République : one of them, Joseph Declercq is its secretary for the Nord from 1919 to 1927. These militants do not limit their action to union work, but found in Halluin several cooperatives. As for the Free Unions House, it propose various activities : music, needlework, drama, cinema. The paper ends with two biographies which show Marc Sangnier's influence on these Christian workers.Les militants chrétiens d'Halluin participent dès 1902 au mouvement du Sillon fondé par Marc Sangnier. Deux ans plus tard, l'un d'eux organise une «Union ouvrière syndicale de l'industrie textile halluinoise» qui sera représentée au congrès constitutif de la C.F.T.C. en 1919. Bon nombre de ces militants participent aux réunions et rencontres départementales de la Jeune République : l'un d'eux, Joseph Declercq en est le secrétaire pour le Nord de 1919 à 1927. Ces militants ne limitent pas leur action au syndicalisme, mais fondent à Halluin plusieurs coopératives. Quant à la Maison des syndicats libres, elle permet diverses activités : musique, couture, art dramatique, cinéma. L'article se termine par deux biographies qui montrent l'influence de Marc Sangnier sur ces ouvriers chrétiens.Léon Saint- Venant en Madeleine Singer, De oorsprong van de C.F.T.C. te Halluin ; le Sillon en la Jeune République. De christelijke militanten werken van 1902 af mee aan de beweging le Sillon, opgericht door Marc Sangnier. Twee jaar later organisert een lid een Union ouvrière syndicale de l'industrie textile hallunoise die zal vertegenwoordigd zijn op het oprichtingscongress van de C.F.T.C. in 1919. Vêle militanten nemen deel aan vergaderingen en departementele samenkonsten van de Jeune République ; een van hen, Joseph Declercq, is secretaris ervan voor het Noor- den van 1919 tot 1927. Deze militanten beperken zich niet tot de syndikale aktie maar richten in Halluin verschillende cooperatieven op. In het Huis van de vrije syndicaten worden allerlei aktiviteiten (muziek, snit, toneel, film) georganiseerd. Het artikel wordt afgesloten met twee biografieën die de invloed van Sangnier op de christelijke arbeiders tonen.Saint-Venant Léon, Singer Madeleine. Aux origines de la C.F.T.C., à Halluin : le Sillon et la Jeune République. In: Revue du Nord, tome 75, n°302, Juillet-septembre 1993. Le personnel politique. pp. 731-748

Pretubulysin : a new option for the treatment of metastatic cancer

Tubulin-binding agents such as taxol, vincristine or vinblastine are well-established drugs in clinical treatment of metastatic cancer. However, because of their highly complex chemical structures, the synthesis and hence the supply issues are still quite challenging. Here we set on stage pretubulysin, a chemically accessible precursor of tubulysin that was identified as a potent microtubule-binding agent produced by myxobacteria. Although much simpler in chemical structure, pretubulysin abrogates proliferation and long-term survival as well as anchorage-independent growth, and also induces anoikis and apoptosis in invasive tumor cells equally potent to tubulysin. Moreover, pretubulysin posseses in vivo efficacy shown in a chicken chorioallantoic membrane (CAM) model with T24 bladder tumor cells, in a mouse xenograft model using MDA-MB-231 mammary cancer cells and finally in a model of lung metastasis induced by 4T1 mouse breast cancer cells. Pretubulysin induces cell death via the intrinsic apoptosis pathway by abrogating the expression of pivotal antiapoptotic proteins, namely Mcl-1 and Bcl-xL, and shows distinct chemosensitizing properties in combination with TRAIL in two- and three-dimensional cell culture models. Unraveling the underlying signaling pathways provides novel information: pretubulysin induces proteasomal degradation of Mcl-1 by activation of mitogen-activated protein kinase (especially JNK (c-Jun N-terminal kinase)) and phosphorylation of Mcl-1, which is then targeted by the SCF(Fbw7) E3 ubiquitin ligase complex for ubiquitination and degradation. In sum, we designate the microtubule-destabilizing compound pretubulysin as a highly promising novel agent for mono treatment and combinatory treatment of invasive cancer

Rechtliche Aspekte der personalisierten Medizin

International audienceOBJECTIVES:The European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Group is developing a computer-adaptive test (CAT) version of the EORTC Quality of Life Questionnaire (QLQ-C30). We evaluated the measurement properties of the CAT versions of physical functioning (PF) and fatigue (FA) and compared these with the corresponding QLQ-C30 scales.STUDY DESIGN AND SETTING:Based on international samples of more than 1,000 cancer patients, we simulated CAT administration of varying numbers of items and compared the resulting scores with those based on all items in the respective item pools. Furthermore, the relative validity (RV) of CATs was compared with that of the QLQ-C30 scales using known groups validity.RESULTS:For both dimensions, CATs of all lengths resulted in unbiased score estimates. CATs consisting of five or more items had reliability>0.90, correlated ≥ 0.97 with the full scale, and had root mean square error <0.25. The average RVs for these CATs ranged 1.02-1.33, indicating possible savings in sample size requirements of 3-42% using CAT.CONCLUSION:The CAT versions of PF and FA exhibited high levels of measurement precision and efficiency. The potential savings in sample size requirements using CATs compared with those using the original QLQ-C30 scales were typically 20% or more

Neuronal Antibody Biomarkers for Sydenham’s Chorea Identify a New Group of Children with Chronic Recurrent Episodic Acute Exacerbations of Tic and Obsessive Compulsive Symptoms Following a Streptococcal Infection

<div><p>Several autoantibodies (anti-dopamine 1 (D1R) and 2 (D2R) receptors, anti-tubulin, anti-lysoganglioside-GM1) and antibody-mediated activation of calcium calmodulin dependent protein kinase II (CaMKII) signaling activity are elevated in children with Sydenham’s chorea (SC). Recognizing proposed clinical and autoimmune similarities between SC and PANDAS (pediatric autoimmune neuropsychiatric disorder associated with a streptococcal infection), we sought to identify serial biomarker changes in a slightly different population. Antineuronal antibodies were measured in eight children (mean 11.3 years) with chronic, dramatic, recurrent tics and obsessive-compulsive disorder (OCD) associated with a group A β-hemolytic streptococcal (GABHS) respiratory tract infection, but differing because they lacked choreiform movements. Longitudinal serum samples in most subjects included two pre-exacerbation samples, Exac), one midst Exac (abrupt recurrence of tic/OCD; temporally association with a GABHS infection in six of eight subjects), and two post-Exac. Controls included four groups of unaffected children (n = 70; mean 10.8 years) obtained at four different institutions and published controls. Clinical exacerbations were not associated with a significant rise in antineuronal antibody titers. CaMKII activation was increased at the GABHS exacerbation point in 5/6 subjects, exceeded combined and published control’s 95th percentile at least once in 7/8 subjects, and median values were elevated at each time point. Anti-tubulin and anti-D2R titers did not differ from published or combined control group’s 95th percentile or median values. Differences in anti-lysoganglioside-GM1 and anti-D1R titers were dependent on the selected control. Variances in antibody titers and CaMKII activation were identified among the institutional control groups. Based on comparisons to published studies, results identify two groups of PANDAS: 1) a cohort, represented by this study, which lacks choreiform movements and elevated antibodies against D2R; 2) the originally reported group with choreiform movements and elevated anti-D2R antibodies, similar to SC. Increased antibody mediated CaMKII activation was found in both groups and requires further study as a potential biomarker.</p></div