The opposite of Dante's hell? The transfer of ideas for social housing at international congresses in the 1850s–1860s

With the advent of industrialization, the question of developing adequate housing for the emergent working classes became more pressing than before. Moreover, the problem of unhygienic houses in industrial cities did not stop at the borders of a particular nation-state; sometimes literally as pandemic diseases spread out 'transnationally'. It is not a coincidence that in the nineteenth century the number of international congresses on hygiene and social topics expanded substantially. However, the historiography about social policy in general and social housing in particular, has often focused on individual cases because of the different pace of industrial and urban development and is thus dominated by national perspectives. In this paper, I elaborate on transnational exchange processes and local adaptations and transformations. I focus on the transfer of the housing model of SOMCO in Mulhouse, (a French house building association) during social international congresses. I examine whether cross-national networking enabled and facilitated the implementation of ideas on the local scale. I will elaborate on the transmission and the local adaptation of the Mulhouse-model in Belgium. Convergences, divergences, and different factors that influenced the local transformations (personal choice, political situation, socioeconomic circumstances) will be taken into accoun

Mowat-Wilson syndrome

Mowat-Wilson syndrome (MWS) is a multiple congenital anomaly syndrome characterized by a distinct facial phenotype (high forehead, frontal bossing, large eyebrows, medially flaring and sparse in the middle part, hypertelorism, deep set but large eyes, large and uplifted ear lobes, with a central depression, saddle nose with prominent rounded nasal tip, prominent columella, open mouth, with M-shaped upper lip, frequent smiling, and a prominent but narrow and triangular pointed chin), moderate-to-severe intellectual deficiency, epilepsy and variable congenital malformations including Hirschsprung disease (HSCR), genitourinary anomalies (in particular hypospadias in males), congenital heart defects, agenesis of the corpus callosum and eye anomalies. The prevalence of MWS is currently unknown, but 171 patients have been reported so far. It seems probable that MWS is under-diagnosed, particularly in patients without HSCR. MWS is caused by heterozygous mutations or deletions in the Zinc finger E-box-binding homeobox 2 gene, ZEB2, previously called ZFHX1B (SIP1). To date, over 100 deletions/mutations have been reported in patients with a typical phenotype; they are frequently whole gene deletions or truncating mutations, suggesting that haploinsufficiency is the main pathological mechanism. Studies of genotype-phenotype analysis show that facial gestalt and delayed psychomotor development are constant clinical features, while the frequent and severe congenital malformations are variable. In a small number of patients, unusual mutations can lead to an atypical phenotype. The facial phenotype is particularly important for the initial clinical diagnosis and provides the hallmark warranting ZEB2 mutational analysis, even in the absence of HSCR. The majority of MWS cases reported so far were sporadic, therefore the recurrence risk is low. Nevertheless, rare cases of sibling recurrence have been observed. Congenital malformations and seizures require precocious clinical investigation with intervention of several specialists (including neonatologists and pediatricians). Psychomotor development is delayed in all patients, therefore rehabilitation (physical therapy, psychomotor and speech therapy) should be started as soon as possible

Phenotype and genotype of 87 patients with Mowat-Wilson syndrome and recommendations for care

Mowat-Wilson syndrome (MWS) is a rare intellectual disability/multiple congenital anomalies syndrome caused by heterozygous mutation of the ZEB2 gene. It is generally underestimated because its rarity and phenotypic variability sometimes make it difficult to recognize. Here, we aimed to better delineate the phenotype, natural history, and genotype-phenotype correlations of MWS.MethodsIn a collaborative study, we analyzed clinical data for 87 patients with molecularly confirmed diagnosis. We described the prevalence of all clinical aspects, including attainment of neurodevelopmental milestones, and compared the data with the various types of underlying ZEB2 pathogenic variations.ResultsAll anthropometric, somatic, and behavioral features reported here outline a variable but highly consistent phenotype. By presenting the most comprehensive evaluation of MWS to date, we define its clinical evolution occurring with age and derive suggestions for patient management. Furthermore, we observe that its severity correlates with the kind of ZEB2 variation involved, ranging from ZEB2 locus deletions, associated with severe phenotypes, to rare nonmissense intragenic mutations predicted to preserve some ZEB2 protein functionality, accompanying milder clinical presentations.ConclusionKnowledge of the phenotypic spectrum of MWS and its correlation with the genotype will improve its detection rate and the prediction of its features, thus improving patient care.GENETICS in MEDICINE advance online publication, 4 January 2018; doi:10.1038/gim.2017.221

Treatment in advanced colorectal cancer: what, when and how?

Treatment of advanced colorectal cancer (CRC) increasingly requires a multidisciplinary approach and multiple treatment options add to the complexity of clinical decision-making. Recently novel targeted therapy against angiogenesis and epidermal growth factor receptor completed a plethora of phase III studies. The addition of bevacizumab to chemotherapy improved the efficacy over chemotherapy alone in both first and second line settings, although the magnitude of benefit may not be as great when a more optimal chemotherapy platform is used. Studies performed thus far did not address conclusively whether bevacizumab should be continued in subsequent lines of treatment. Anti-angiogenesis tyrosine kinase inhibitors have not shown any additional benefit over chemotherapy alone so far. Although some benefits were seen with cetuximab in all settings of treating advanced CRC, K-ras mutation status provides an important determinant of who would not benefit from such a treatment. Caution should be exercised in combining anti-angiogenesis with anti-EGFR strategy until further randomised data become available. In this review, we have focused on the implications of these trial results on the everyday management decisions of treating advanced CRC

Ifosfamide given once every other week: A clinical and pharmacological study

13008 Background. Ifosfamide (IFM) is a bi-functional alkylator with wide spectrum of activity in solid tumors and has an auto-inductive liver metabolism through P450 cytochromes. Auto-induction might permit a better therapeutic index for combination therapy. Methods. A phase I trial with interpatient dose escalation of a single dose of IFM given every 2 wks in advanced solid tumor pts. IFM, its dechloroethylated and active 4-hydroxy metabolites, were measured at cycle 1 &amp; 2 at the end of infusion, 2 and 5h later, using gas chromatography. IFM elimination was considered as following a monocompartimental model kinetics. Results From January 2004 to June 2006; 20 pts of PS&lt;2 were included :10 F, 10 M, median age 61 years (39–78), median previous chemotherapies: 2 (0–5). Primary tumor was most often ovarian (5), peritoneal (3), sarcoma (2), melanoma (2), or miscellaneous (8). 10 pts received 2.5g/m2 and other 10 pts received 3g/m2. A total of 79 cycles were evaluable for toxicity. median number of cycles: 4 (1–8). No Grade (Gr) 3–4 hematologic toxicity, no alopecia. Gr2 nausea and fatigue were the most common toxicities at 3g/m2. No toxicity-related fatal event was noted. One objective response was noted in pancreatic cancer pt and one sustained CA125 decline in a heavily pretreated ovarian cancer pt. A slight (7–10%) but reproducible decrease of AUC was detectable at cycle 2, at both dose levels, related to auto-inductive metabolism (see table below). The other PK results are available and will be presented (Table). Intra individual variations (large SD) were noticed for each pharmacokinetic (PK) parameter. Conclusions: A slight non dose- dependent but rather patient-dependent auto-induction of IFM metabolism was detected. The toxicity profile allows the development of every 2 wks IFM-based combination therapies. [Table: see text] No significant financial relationships to disclose. </jats:p

Reversible tumor metastases growth acceleration following bevacizumab interruption and surgical resection of metastases

14119 Background: The addition of bevacizumab (BV), an anti-VEGF monoclonal antibody with antiangiogenic activity, to cytotoxic chemotherapy (CH) improves survival in metastatic colorectal cancer patients (pts). Reversal of VEGF inhibition is associated with rapid vascular regrowth in tumors in vivo (M.R. Mancuso et al, J Clin Invest; 116(10): 2610–2621, 2006). In the clinical setting, the consequences of BV interruption are poorly documented, especially in interactions with the surgical resection of liver metastases. Methods: We describe the kinetics of tumor growth prior to, during, and after interruption of BV and under BV reintroduction, in consecutive colorectal cancer pts experiencing objective response under CH+BV, followed by surgical resection of metastases. We measured either clinically, of using CT-scan, the diameter of target lesions according to RECIST criteria, and the doubling time. Results: 7 pts (3 F, 4M), with median age of 54 years (41–70), were treated with 5-FU based CH (+oxaliplatin: 5; + irinotecan: 1 pt) and BV for metastatic colo- (6 pts) rectal (1 pt) cancer received a median number of 6 (4–18) cycles. Median time between BV interruption and surgery: 8 weeks (3–12). Under BV, all pts experienced objective response, with a median tumor reduction of 13%/month (extr: 6–15%). After BV interruption, under CH alone, 2/7 pts experienced disease progression, with a tumor growth of the residual disease of +7% and +200%/month, respectively. In pts who underwent surgery, during the off therapy period, tumor growth occurred in all 7 pts with a kinetics of +17 to +400%/month. Tumor growth doubling time after BV interruption ranged between 2 and 5 weeks. Reintroduction of BV re-induced a tumor response in 5/7 pts with a median time to response of 8 weeks (6–12) and a reduction of 10%/month. Conclusions: We show reproducible evidence of tumor growth acceleration following BV interruption. Surgery might transiently modify the balance between angiogenic and anti-angiogenic factors. We suggest to reduce the duration of BV interruption and to restart BV as soon as possible after surgery. These observations justify a large prospective analysis of the variations of tumor growth in this setting. No significant financial relationships to disclose. </jats:p