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Christopher Jencks' book 'The Homeless' analyzes the possible reasons for the growing number of homeless people and suggests possible measures. Homelessness may be due to the inability of the mental health system to care for mental patients outside institutions, the proliferation of crack cocaine, the reduction of job opportunities and the massive replacement of low-cost hotels and lodges by expensive hotels. Jencks' suggestions include the provision of jobs for single mothers and the establishment of services for the those who cannot work., Over the last decade and a half, substantive political, economic, and social transformations have produced a rapid growth in the number of homeless people within the United States. In The [...]

Over the last decade and a half, substantive political, economic, and social transformations have produced a rapid growth in the number of homeless people within the United States. In The [...]

Stargardt disease (STGD1) is an autosomal recessive retinal dystrophy due to mutations in ABCA4, characterized by subretinal deposition of lipofuscin-like substances and bilateral centrifugal vision loss. Despite the tremendous progress made in the understanding of STGD1, there are no approved treatments to date. This review examines the challenges in the development of an effective STGD1 therapy. A literature review was performed through to June 2021 summarizing the spectrum of retinal phenotypes in STGD1, the molecular biology of ABCA4 protein, the in vivo and in vitro models used to investigate the mechanisms of ABCA4 mutations and current clinical trials. STGD1 phenotypic variability remains an challenge for clinical trial design and patient selection. Pre-clinical development of therapeutic options has been limited by the lack of animal models reflecting the diverse phenotypic spectrum of STDG1. Patient-derived cell lines have facilitated the characterization of splice mutations but the clinical presentation is not always predicted by the effect of specific mutations on retinoid metabolism in cellular models. Current therapies primarily aim to delay vision loss whilst strategies to restore vision are less well developed. STGD1 therapy development can be accelerated by a deeper understanding of genotype-phenotype correlations. [ABSTRACT FROM AUTHOR]

Abstract Background Antisense oligomer induced exon skipping aims to reduce the severity of Duchenne muscular dystrophy by redirecting splicing during pre-RNA processing such that the causative mutation is by-passed and a shorter but partially functional Becker muscular dystrophy-like dystrophin isoform is produced. Normal exons are generally targeted to restore the dystrophin reading frame however, an appreciable subset of dystrophin mutations are intra-exonic and therefore have the potential to compromise oligomer efficiency, necessitating personalised oligomer design for some patients. Although antisense oligomers are easily personalised, it remains unclear whether all patient polymorphisms within antisense oligomer target sequences will require the costly process of producing and validating patient specific compounds. Methods Here we report preclinical testing of a panel of splice switching antisense oligomers, designed to excise exon 25 from the dystrophin transcript, in normal and dystrophic patient cells. These patient cells harbour a single base insertion in exon 25 that lies within the target sequence of an oligomer shown to be effective at removing exon 25. Results It was anticipated that such a mutation would compromise oligomer binding and efficiency. However, we show that, despite the mismatch an oligomer, designed and optimised to excise exon 25 from the normal dystrophin mRNA, removes the mutated exon 25 more efficiently than the mutation-specific oligomer. Conclusion This raises the possibility that mismatched AOs could still be therapeutically applicable in some cases, negating the necessity to produce patient-specific compounds.

Author(s): Julia Alter [1]; Fang Lou [2]; Adam Rabinowitz [1]; HaiFang Yin [1]; Jeffrey Rosenfeld [3]; Steve D Wilton [4]; Terence A Partridge [1]; Qi Long Lu (corresponding author) [3] [...]

Mutations in the splicing factor pre-messenger RNA processing factor 31 (PRPF31) gene cause autosomal dominant retinitis pigmentosa 11 (RP11) through a haplo-insufficiency mechanism. We describe the phenotype and progression of microperimetry and autofluorescence endpoints in an Indigenous Australian RP11 family. Ophthalmic examination, optical coherence tomography, fundus autofluorescence and microperimetry were performed at baseline and every 6–12 months. Baseline and annual change in best-corrected visual acuity (BCVA), microperimetry mean sensitivity (MS) and number of scotoma loci, residual ellipsoid zone (EZ) span and hyperautofluorescent ring (HAR) area were reported. Next-generation and Sanger sequencing were performed in available members. 12 affected members from three generations were examined. Mean (SD, range) age at onset of symptoms was 11 (4.5, 4–19) years. MS declined steadily from the third decade and EZ span and HAR area declined rapidly during the second decade. Serial microperimetry showed negligible change in MS over 2–3 years. However, mean EZ span, near-infrared and short-wavelength HAR area reduction was 203 (6.4%) µm/year, 1.8 (8.7%) mm2/year and 1.1 (8.6%) mm2/year, respectively. Genetic testing was performed on 11 affected and 10 asymptomatic members and PRPF31 c.1205 C > A (p.Ser402Ter) mutation was detected in all affected and two asymptomatic members (non-penetrant carriers). Our findings suggest that in the studied cohort, the optimal window for therapeutic intervention is the second decade of life and residual EZ span and HAR area can be considered as efficacy outcome measures. Further studies on larger samples with different PRPF31 mutations and longer follow-up duration are recommended. [ABSTRACT FROM AUTHOR]

In this paper, I look at the use of qualitative methods in health geography. I focus on two projects using in-depth interviews with people with HIV/AIDS. Drawing from feminist work on qualitative methodologies and the production of knowledge, two questions are posed. First, what insights do interviews offer about people's daily experiences with HIV/AIDS? Second, given that interviews involve direct contact between interviewer and respondent, what are the implications of using this methodology? Projects reveal that living with HIV/AIDS involves a complex series of negotiations. These include negotiating one's own identity within medical discourse, dealing with health care professionals, and choosing how to use medication. The projects also indicate that qualitative research itself involves a process of negotiation. Researchers' preconceptions, interview settings and formats, and relationships established during research can effect research outcomes and research participants. I argue that a willingness to reflect critically on the use of qualitative methods is needed to safeguard against these unintended consequences. Key Words: qualitative methods, in-depth interviews, HIV/AIDS, health.