Pluralising critical technical practice

In this special issue, we turn to ideas of and approaches to critical technical practices (CTPs) as entry points to doing critique and doing things critically in digitally mediated cultures and societies. We explore the pluralisation of ‘critical technical practice’, starting from its early formulations in the context of AI research and development (Agre, 1997a, 1997b) to the many ways in which it has resonated and been taken up by different publications, projects, groups, and communities of practice, and what is has come to mean. Agre defined CTP as a situational, practical, and constructive way of working: ‘a technical practice for which critical reflection upon the practice is part of the practice itself’ (1997a: XII). Communities of practice in which the notion has been adopted, adapted, and put to use range from human–computer interaction (HCI) to media art and pedagogy, from science and technology studies (STS) and computer-supported cooperative work (CSCW) to digital humanities, media studies and data studies. This special issue affirms the pluralisation of CTP, and serves as an invitation to (re)consider what it means to use this notion drawing on a wider body of work, including beyond Agre. In this introduction, we review and discuss CTPs according to (1) Agre, (2) indexed research, and (3) contributors to this special issue. We conclude with some questions and considerations for those interested in working with this notion

Identification and characterisation of putative drug binding sites in human ATP-binding cassette B5 (ABCB5) transporter.

The human ATP-binding cassette B5 (ABCB5) transporter, a member of the ABC transporter superfamily, is linked to chemoresistance in tumour cells by drug effluxion. However, little is known about its structure and drug-binding sites. In this study, we generated an atomistic model of the full-length human ABCB5 transporter with the highest quality using the X-ray crystal structure of mouse ABCB1 (Pgp1), a close homologue of ABCB5 and a well-studied member of the ABC family. Molecular dynamics simulations were used to validate the atomistic model of ABCB5 and characterise its structural properties in model cell membranes. Molecular docking simulations of known ABCB5 substrates such as taxanes, anthracyclines, camptothecin and etoposide were then used to identify at least three putative binding sites for chemotherapeutic drugs transported by ABCB5. The location of these three binding sites is predicted to overlap with the corresponding binding sites in Pgp1. These findings will serve as the basis for future in vitro studies to validate the nature of the identified substrate-binding sites in the full-length ABCB5 transporter

Melanoma circulating tumor cells: Benefits and challenges required for clinical application

© 2018 The implementation of novel therapeutic interventions has improved the survival rates of melanoma patients with metastatic disease. Nonetheless, only 33% of treated cases exhibit long term responses. Circulating tumor cell (CTC) measurements are currently of clinical value in breast, prostate and colorectal cancers. However, the clinical utility of melanoma CTCs (MelCTCs) is still unclear due to challenges that appear intrinsic to MelCTCs (i.e. rarity, heterogeneity) and a lack of standardization in their isolation, across research laboratories. Here, we review the latest developments, pinpoint the challenges in MelCTC isolation and address their potential role in melanoma management

Are women residency supervisors obligated to nurture?

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73923/1/j.1365-2929.2006.02635.x.pd

Correlates of absolute and excessive weight gain during pregnancy

OBJECTIVE: Factors associated with weight gain during pregnancy that may be linked to maternal overweight and obesity were examined. METHODS: In this observational study, 144 women reported on demographics, (prepregnancy) body weight, and lifestyles in self-reported questionnaires at 30 weeks gestation. Body weight at the end of pregnancy (self-reported at 6 weeks postpartum) was used to determine total gestational weight gain. Multivariate prediction models were developed to identify factors associated with total gestational weight gain and excessive gestational weight gain (i.e., higher weight gain than recommended by the Institute of Medicine). RESULTS: Women gained 14.4 (+/-5.0) kg during pregnancy. Obese women gained almost 4 kg less than normal weight women. Pregnant women judging themselves to be less physically active or women who reported increased food intakes during pregnancy gained significantly more weight. Over one third of women (38%) gained more weight than recommended. Being overweight, judging yourself to be less physically active than others, and a perceived elevated food intake during pregnancy were significantly associated with excessive weight gain (odds ratio [OR] = 6.33, 95% confidence interval [CI]: 2.01-19.32; OR = 3.96, 95% CI: 1.55l, 10.15; and OR = 3.14, 95% CI: 1.18, 8.36, respectively). A higher age at menarche and hours of sleep reduced the odds for excessive weight gain (OR = 0.75, 95% CI: 0.57, 0.99; and OR = 0.35, 95% CI: 0.57, 0.93, respectively). CONCLUSIONS: Mean hours of sleep, perceived physical activity, and measures of food intake at 30 weeks gestation were identified as modifiable behavioral correlates for excessive gestational weight gain. Strategies to optimize gestational weight gain need to be explored, with a focus on the identified factors

Isolation and detection of circulating tumour cells from metastatic melanoma patients using a slanted spiral microfluidic device.

Circulating Tumour Cells (CTCs) are promising cancer biomarkers. Several methods have been developed to isolate CTCs from blood samples. However, the isolation of melanoma CTCs is very challenging as a result of their extraordinary heterogeneity, which has hindered their biological and clinical study. Thus, methods that isolate CTCs based on their physical properties, rather than surface marker expression, such as microfluidic devices, are greatly needed in melanoma. Here, we assessed the ability of the slanted spiral microfluidic device to isolate melanoma CTCs via label-free enrichment. We demonstrated that this device yields recovery rates of spiked melanoma cells of over 80% and 55%, after one or two rounds of enrichment, respectively. Concurrently, a two to three log reduction of white blood cells was achieved with one or two rounds of enrichment, respectively. We characterised the isolated CTCs using multimarker flow cytometry, immunocytochemistry and gene expression. The results demonstrated that CTCs from metastatic melanoma patients were highly heterogeneous and commonly expressed stem-like markers such as PAX3 and ABCB5. The implementation of the slanted microfluidic device for melanoma CTC isolation enables further understanding of the biology of melanoma metastasis for biomarker development and to inform future treatment approaches

Multiplexed, High Density Electrophysiology with Nanofabricated Neural Probes

Extracellular electrode arrays can reveal the neuronal network correlates of behavior with single-cell, single-spike, and sub-millisecond resolution. However, implantable electrodes are inherently invasive, and efforts to scale up the number and density of recording sites must compromise on device size in order to connect the electrodes. Here, we report on silicon-based neural probes employing nanofabricated, high-density electrical leads. Furthermore, we address the challenge of reading out multichannel data with an application-specific integrated circuit (ASIC) performing signal amplification, band-pass filtering, and multiplexing functions. We demonstrate high spatial resolution extracellular measurements with a fully integrated, low noise 64-channel system weighing just 330 mg. The on-chip multiplexers make possible recordings with substantially fewer external wires than the number of input channels. By combining nanofabricated probes with ASICs we have implemented a system for performing large-scale, high-density electrophysiology in small, freely behaving animals that is both minimally invasive and highly scalable

Pneumococcal carriage in sub-Saharan Africa--a systematic review.

BACKGROUND: Pneumococcal epidemiology varies geographically and few data are available from the African continent. We assess pneumococcal carriage from studies conducted in sub-Saharan Africa (sSA) before and after the pneumococcal conjugate vaccine (PCV) era. METHODS: A search for pneumococcal carriage studies published before 2012 was conducted to describe carriage in sSA. The review also describes pneumococcal serotypes and assesses the impact of vaccination on carriage in this region. RESULTS: Fifty-seven studies were included in this review with the majority (40.3%) from South Africa. There was considerable variability in the prevalence of carriage between studies (I-squared statistic = 99%). Carriage was higher in children and decreased with increasing age, 63.2% (95% CI: 55.6-70.8) in children less than 5 years, 42.6% (95% CI: 29.9-55.4) in children 5-15 years and 28.0% (95% CI: 19.0-37.0) in adults older than 15 years. There was no difference in the prevalence of carriage between males and females in 9/11 studies. Serotypes 19F, 6B, 6A, 14 and 23F were the five most common isolates. A meta-analysis of four randomized trials of PCV vaccination in children aged 9-24 months showed that carriage of vaccine type (VT) serotypes decreased with PCV vaccination; however, overall carriage remained the same because of a concomitant increase in non-vaccine type (NVT) serotypes. CONCLUSION: Pneumococcal carriage is generally high in the African continent, particularly in young children. The five most common serotypes in sSA are among the top seven serotypes that cause invasive pneumococcal disease in children globally. These serotypes are covered by the two PCVs recommended for routine childhood immunization by the WHO. The distribution of serotypes found in the nasopharynx is altered by PCV vaccination