A discussion of the housing problems of young people & of the broader aspects of the Yugoslav housing crisis. A more complex approach should be taken to the analysis of the structure of housing space ...from the standpoint of the values of its individual components. A 1973 study is cited in which respondents (a sample of young people) were asked to what degree, if any, their housing conditions impaired their accustomed lifestyle: 30.5% reported moderate impairment, 27.4% none, 17.7% some, 13.5% considerable, & 11% significant impairment. The study revealed a positive correlation between the amount of housing space enjoyed & freedom from impairment. An even more significant correlation exists between having the privacy of one's own room & freedom from impairment. Housing space may not be the primary problem, but survey results leave no doubt of its significance. Modified HA.
Housing problems of young people (pupils, students, young working people) as well as broader aspects of housing problems are dealt with in this paper. In the first part, the authors give a warning ...about the still insufficiently defined criteria of use value of housing space as complex categories, and about the basic technologizing of discussions of housing problems at the level of a simple satisfaction of basic human needs. The idea is presented about the need for a more complex approach to the analysis of the structure of housing space from the standpoint of the values of individual components which make up a dynamic »picture« of housing space. In this sense, comments are made on the basic results of a study which was conducted during the last two years in a population of pupils, students and young workers, and which has since been published as a book Problemi stanovanja mladih (The Housing Problems of Youth), CDD, Zagreb, 1978.
The authors are particularly informed about the »picture of housing space« and they assert that it is complementary. That is, in addition to »physical« characteristics, an evaluation of the quality of given housing space is also dependent on many »experiential« characteristics (the opportunity to independently perform various activities, the degree of isolation, the degree to which the space is disturbance-free, etc.). The basic conclusion which is drawn is the following: perception of housing space is complementary and relatively indivisible. In other words, if there is a clear disharmony between individual elements which complete the »picture of housing space«, it is then difficult to talk about quality. This is likewise the case when individual elements of the »picture« are substandard.
Department of Kinesiology, Pennsylvania State University, University Park, Pennsylvania 16802
Submitted 15 January 2004
; accepted in final form 27 February 2004
We studied age-related changes in the ...performance of maximal and accurate submaximal force and moment production tasks. Elderly and young subjects pressed on six dimensional force sensors affixed to a handle with a T-shaped attachment. The weight of the whole system was counterbalanced with another load. During tasks that required the production of maximal force or maximal moment by all of the digits, young subjects were stronger than elderly. A greater age-related deficit was seen in the maximal moment production tests. During maximal force production tests, elderly subjects showed larger relative involvement of the index and middle fingers; they moved the point of thumb force application upward (toward the index and middle fingers), whereas the young subjects rolled the thumb downward. During accurate force/moment production trials, elderly persons were less accurate in the production of both total moment and total force. They produced higher antagonistic moments, i.e., moment by fingers that acted against the required direction of the total moment. Both young and elderly subjects showed negative covariation of finger forces across repetitions of a ramp force production task. In accurate moment production tasks, both groups showed negative covariation of two components of the total moment: those produced by the normal forces and those produced by the tangential forces. However, elderly persons showed lower values of the indexes of both finger force covariation and moment covariation. We conclude that age is associated with an impaired ability to produce both high moments and accurate time profiles of moments. This impairment goes beyond the well-documented deficits in finger and hand force production by elderly persons. It involves worse coordination of individual digit forces and of components of the total moment. Some atypical characteristics of finger forces may be viewed as adaptive to the increased variability in the force production with age.
force; moment; human
Address for reprint requests and other correspondence: M. L. Latash, Dept. of Kinesiology, Rec. Hall-267, The Pennsylvania State Univ., Univ. Park, PA 16802 (E-mail: mll11{at}psu.edu ).
Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is a new drug delivery method offered in selected patients suffering from non-resectable peritoneal carcinomatosis (PC). As reported ...experience is still limited, we conducted a survey among active PIPAC centers aiming to report their technical approach and clinical findings.
An online survey was sent to active PIPAC centers worldwide. The questionnaire consisted of 34 closed questions and was conducted over a period of 3 months beginning in March 2017.
Nine out of 15 contacted centers completed the questionnaire totaling 832 PIPAC procedures in 349 patients. Most common indications for PIPAC were PC from gastric, ovarian and colorectal origin. The mean time between each PIPAC procedure was 6–8 weeks. Seven of nine (77.8%) centers evaluate the PCI at every PIPAC procedure. At least four tissue samples for histopathology analysis were retrieved in 5 (55.6%). All centers (100%) use the same chemotherapy protocol: oxaliplatin at a dosage of 92mg/m2 for PC of colorectal origin and a combination of cisplatin and doxorubicin at a dosage of 7.5mg/m2 and 1.5mg/m2, respectively, for other types of PC. Eight centers (88.9%) perform routine radiological evaluation before first PIPAC and after third PIPAC.
These data confirm that PIPAC procedures are homogeneously performed in established centers. Standardization of the procedure will facilitate future international multicenter prospective clinical trials.
We report an infant with sickle cell disease phenotype by biochemical analysis whose beta-globin gene (HBB) sequencing showed sickle cell mutation (HBBS) heterozygosity. The proband has a unique ...head-to-tail duplication of the beta-globin gene cluster having wild-type (HBBA) and HBBS alleles inherited from her father; constituting her HBBS/HBBS-HBBA genotype. Further analyses revealed that proband's duplicated beta-globin gene cluster (650 kb) encompassing HBBA does not include the immediate upstream locus control region (LCR) or 3' DNase I hypersensitivity (HS) element. The LCR interacts with beta-globin gene cluster involving long range DNA interactions mediated by various transcription factors to drive the regulation of globin genes expression. However, a low level of HBBA transcript was clearly detected by digital PCR. In this patient, the observed transcription from the duplicated, distally displaced HBBA cluster demonstrates that the loss of LCR and flanking 3'HS sites do not lead to complete silencing of HBB transcription.
Transcriptional regulation of β-globin cluster genes follows a complex, highly conserved system of gene expression with developmental and tissue-specific control. The DNase I hypersensitivity (HS) ...sites in the upstream locus control region (LCR) and 3' HS1 element are thought to interact with β-globin cluster genes involving long range DNA interactions mediated by various transcription factors to drive the regulation of β-like globin gene expression. The majority of studies have focused on the role of the LCR on active transcription and globin gene switching. Various in vitro and in vivo studies have shown that the LCR interacts with one gene at a time and that absence of the LCR results in a dramatic decrease (10 -100 fold) in globin transcripts (Kiefer et. al., Mutat. Res. 2008, 647:68, Noordermeer et. al., IUBMB Life 2008, 60: 824). However, the role of the 3'HS1 downstream and other distal cis -regulatory elements are not entirely understood, with recent studies in mouse and cell-culture models suggesting they play a role in the insulation of globin genes from silencing chromatin (Bender et. al., Blood 2008, 106: 1395). Our knowledge of the β-globin LCR and 3'HS1 function is still incomplete and much can still be learned from human mutations affecting these regulatory elements.
We report a unique head-to-tail duplication of the β-globin cluster in a patient phenotypically expressing homozygous HbS (sickle-cell anemia, SCA) that provides insight into the regulatory role of the β-LCR and 3'HS1 on wild-type β-globin (β-A) expression in a background of SCA. The studies were driven by an apparent discrepancy between hemoglobin analysis of an infant with a SCA phenotype and no detectable HBA, and Sanger sequencing of the β-globin genes which showed a heterozygous genotype.
Analyses of parents' blood samples and DNA revealed that each were carriers for sickle cell allele. Hemoglobin analysis showed the father expressed HbS fraction at 41.3% and the mother at 33.3%, while the proband had a majority of HbS, some HbF and no detectable HbA. The reduced HbS fraction in the mother could be explained by co-inheritance of α-thalassemia (αα/α-3.7). The proband did not inherit α-thalassemia from the mother.
Multiplex ligation-dependent probe amplification analysis of the proband's DNA suggested duplication of the β-globin cluster, resulting in three copies of the HBB gene in the genome. Subsequent next-generation sequencing confirmed that the duplication occurred immediately adjacent to the first iteration of sequence, in head-to-tail orientation and resulted in an intact β-S cluster having both LCR and HS1 elements, followed by the duplicated β-A cluster (β-S, β-A) that excluded a part of HBE (epsilon globin) and the upstream β-LCR regions, extending through to LINE L1LBP1 (hg19 chr11:4640332-5290168). Further analyses revealed that the duplicated β-A cluster, which encompassed approximately 650 kb sequence, lacked a DNA segment containing the 3'HS1 element (figure 1). The proband's β genotype is thus (β-S/β-S, β-A). DNA analysis showed that the father carried the duplicated β-globin cluster with genotype (β-A/β-S, β-A), and the mother, a heterozygous HbS genotype (β-A/β-S).
Reverse transcription, quantitative polymerase chain reaction (RT-qPCR) was used to assess transcription levels of β-A and β-S mRNA for each family member. Analysis of the parents' reticulocyte RNA showed that the β-globin (β-A and β-S) transcript levels were nearly balanced. RT-qPCR of proband's reticulocyte RNA showed no convincing detection of β-A transcript, but the β-A transcript was clearly detected by digitalPCR, albeit at a very low level (0.4% of total HBB transcript) (figure 2).
The β-globin cluster duplication on one chromosome in a background of a phenotypically homozygous (HbSS) SCA patient has provided a unique opportunity to assess the effect of the LCR and 3'HS1 regions on the transcription of a β-A gene in an unbiased environment. Prior studies in transformed cell-lines or mouse models have shown the down regulatory effect of LCR loss and potential protective effect of the 3'HS1 element. Within the human model, the observed transcription from the duplicated, distally displaced (~650 kb) β-A cluster demonstrates that the loss of LCR and flanking HS sites does not lead to complete silencing of β-globin transcription.
VD was supported by project IGA MzCR NT13587.
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No relevant conflicts of interest to declare.
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