Impact of anti-thymocyte globulin dose for graft-versus-host disease prophylaxis in allogeneic hematopoietic cell transplantation from matched unrelated donors: a multicenter experience.

Despite the widespread use of rabbit anti-thymocyte globulin (ATG) to prevent acute and chronic graft-versus-host disease (aGVHD, cGVHD) after allogeneic hematopoietic cell transplantation (allo-HCT), convincing evidence about an optimal dose is lacking. We retrospectively evaluated the clinical impact of two different ATG doses (5 vs 6-7.5 mg/kg) in 395 adult patients undergoing HSCT from matched unrelated donors (MUD) at 3 Italian centers. Cumulative incidence of aGVHD and moderate-severe cGVHD did not differ in the 2 groups. We observed a trend toward prolonged overall survival (OS) and disease-free survival (DFS) with lower ATG dose (5-year OS and DFS 56.6% vs. 46.3%, p=0.052, and 46.8% vs. 38.6%, p=0.051, respectively) and no differences in relapse incidence and non-relapse mortality. However, a significantly increased infection-related mortality (IRM) was observed in patients who received a higher ATG dose (16.7% vs. 8.8% in the lower ATG group, p=0.019). Besides, graft and relapse-free survival (GRFS) was superior in the lower ATG group (5-year GRFS 43.1% vs. 32.4%, p=0.014). The negative impact of higher ATG dose on IRM and GRFS was confirmed by multivariate analysis. Our results suggest that ATG doses higher than 5 mg/kg are not required for MUD allo-HCT and seem associated with worse outcomes.

Simple, Scalable Proteomic Imaging for High-Dimensional Profiling of Intact Systems.

Combined measurement of diverse molecular and anatomical traits that span multiple levels remains a major challenge in biology. Here, we introduce a simple method that enables proteomic imaging for scalable, integrated, high-dimensional phenotyping of both animal tissues and human clinical samples. This method, termed SWITCH, uniformly secures tissue architecture, native biomolecules, and antigenicity across an entire system by synchronizing the tissue preservation reaction. The heat- and chemical-resistant nature of the resulting framework permits multiple rounds (>20) of relabeling. We have performed 22 rounds of labeling of a single tissue with precise co-registration of multiple datasets. Furthermore, SWITCH synchronizes labeling reactions to improve probe penetration depth and uniformity of staining. With SWITCH, we performed combinatorial protein expression profiling of the human cortex and also interrogated the geometric structure of the fiber pathways in mouse brains. Such integrated high-dimensional information may accelerate our understanding of biological systems at multiple levels.

Stochastic electrotransport selectively enhances the transport of highly electromobile molecules.

Nondestructive chemical processing of porous samples such as fixed biological tissues typically relies on molecular diffusion. Diffusion into a porous structure is a slow process that significantly delays completion of chemical processing. Here, we present a novel electrokinetic method termed stochastic electrotransport for rapid nondestructive processing of porous samples. This method uses a rotational electric field to selectively disperse highly electromobile molecules throughout a porous sample without displacing the low-electromobility molecules that constitute the sample. Using computational models, we show that stochastic electrotransport can rapidly disperse electromobile molecules in a porous medium. We apply this method to completely clear mouse organs within 1-3 days and to stain them with nuclear dyes, proteins, and antibodies within 1 day. Our results demonstrate the potential of stochastic electrotransport to process large and dense tissue samples that were previously infeasible in time when relying on diffusion.

An Online, Moderated Peer-to-Peer Support Bulletin Board for Depression: User-Perceived Advantages and Disadvantages.

BACKGROUND: Online, peer-to-peer support groups for depression are common on the World Wide Web and there is some evidence of their effectiveness. However, little is known about the mechanisms by which Internet support groups (ISGs) might work. OBJECTIVE: This study aimed to investigate consumer perceptions of the benefits and disadvantages of online peer-to-peer support by undertaking a content analysis of the spontaneous posts on BlueBoard, a well-established, moderated, online depression bulletin board. METHODS: The research set comprised all posts on the board (n=3645) for each of 3 months selected at 4 monthly intervals over 2011. The data were analyzed using content analysis and multiple coders. RESULTS: A total of 586 relevant posts were identified, 453 (77.3%) reporting advantages and 133 (22.7%) reporting disadvantages. Positive personal change (335/453, 74.0%) and valued social interactions and support (296/453, 65.3%) emerged as perceived advantages. Other identified benefits were valued opportunities to disclose/express feelings or views (29/453, 6.4%) and advantages of the BlueBoard environment (45/453, 9.9%). Disadvantages were negative personal change (50/133, 37.6%), perceived disadvantages of board rules/moderation (42/133, 31.6%), unhelpful social interactions/contact with other members (40/133, 30.1%), and technical obstacles to using the board (14/133, 10.5%). CONCLUSIONS: Consumers value the opportunity to participate in an online mutual support group for mental health concerns. Further research is required to better understand how and if these perceived advantages translate into positive outcomes for consumers, and whether the perceived disadvantages of such boards can be addressed without compromising the safety and positive outcomes of the board.

Two experimental tests of relational models of procedural justice: non-instrumental voice and authority group membership.

In both a laboratory experiment (in Australia) using university as the basis of group membership, and a scenario experiment (in India) using religion as the basis of group membership, we observe more favourable respect and fairness ratings in response to an in-group authority than an out-group authority who administers non-instrumental voice. Moreover, we observe in our second experiment that reported likelihood of protest (herein called "social-change voice") was relatively high following non-instrumental voice from an out-group authority, but relatively low following non-instrumental voice from an in-group authority. Our findings are consistent with relational models of procedural justice, and extend the work by examining likely use of alternative forms of voice as well as highlighting the relative importance of instrumentality.

Multiplex amplification of large sets of human exons.

A new generation of technologies is poised to reduce DNA sequencing costs by several orders of magnitude. But our ability to fully leverage the power of these technologies is crippled by the absence of suitable 'front-end' methods for isolating complex subsets of a mammalian genome at a scale that matches the throughput at which these platforms will routinely operate. We show that targeting oligonucleotides released from programmable microarrays can be used to capture and amplify approximately 10,000 human exons in a single multiplex reaction. Additionally, we show integration of this protocol with ultra-high-throughput sequencing for targeted variation discovery. Although the multiplex capture reaction is highly specific, we found that nonuniform capture is a key issue that will need to be resolved by additional optimization. We anticipate that highly multiplexed methods for targeted amplification will enable the comprehensive resequencing of human exons at a fraction of the cost of whole-genome resequencing.