The home-self and out-of-home placement: The home concept among adults educated in their childhood at a residential care setting

This study proposes to examine the phenomenology of home among 46 Israeli adults who had been deemed "at-risk children" and removed from their home by court order in their childhood on the grounds of parental mistreatments, such as abuse and neglect. For a comprehensive understanding of the long-term impact of out-of-home placement, adults of different ages were interviewed. The research findings reflect the close connection between home concept and self-concept, a long-standing internal dialectic between the home that did not exist and the home (as an internal-emotional space) that the adults would have liked to have. Furthermore, our findings reveal what we term the life career of the home concept, that is, the various diachronic phenomenological definitions that adults grant to the home-self in childhood, anchored in the family home, during their time in a residential care setting, their adolescence, and their adulthood. The discussion addresses the unique self-concept and home concept of care leavers.     

Analysis and correction of crosstalk effects in pathway analysis

Identifying the pathways that are significantly impacted in a given condition is a crucial step in understanding the underlying biological phenomena. All approaches currently available for this purpose calculate a P-value that aims to quantify the significance of the involvement of each pathway in the given phenotype. These P-values were previously thought to be independent. Here we show that this is not the case, and that many pathways can considerably affect each other''s P-values through a “crosstalk” phenomenon. Although it is intuitive that various pathways could influence each other, the presence and extent of this phenomenon have not been rigorously studied and, most importantly, there is no currently available technique able to quantify the amount of such crosstalk. Here, we show that all three major categories of pathway analysis methods (enrichment analysis, functional class scoring, and topology-based methods) are severely influenced by crosstalk phenomena. Using real pathways and data, we show that in some cases pathways with significant P-values are not biologically meaningful, and that some biologically meaningful pathways with nonsignificant P-values become statistically significant when the crosstalk effects of other pathways are removed. We describe a technique able to detect, quantify, and correct crosstalk effects, as well as identify independent functional modules. We assessed this novel approach on data from four experiments involving three phenotypes and two species. This method is expected to allow a better understanding of individual experiment results, as well as a more refined definition of the existing signaling pathways for specific phenotypes.The correct identification of the signaling and metabolic pathways involved in a given phenotype is a crucial step in the interpretation of high-throughput genomic experiments. Most approaches currently available for this purpose treat the pathways as independent. In fact, pathways can affect each other''s P-values through a phenomenon we refer to as crosstalk. This crosstalk may be due to the regulatory interactions among different pathways or to the gene overlap among pathways. In this work, we will use the term crosstalk to refer to the effect that pathways exercise on each other due to the presence of overlapping genes. Although it is intuitive that various pathways could influence each other, especially when they share genes, the presence and extent of this phenomenon have not been rigorously studied and, most importantly, there is no currently available technique able to quantify the amount of such crosstalk. There are three major categories of methods that aim to identify significant pathways: enrichment analysis (e.g., Fisher''s exact test–hypergeometric) (Tavazoie et al. 1999; Draghici et al. 2003); functional scoring (e.g., GSEA) (Mootha et al. 2003; Subramanian et al. 2005); and topology-based methods (e.g., impact analysis) (Draghici et al. 2007; Tarca et al. 2009). Another classification of gene set analysis methods is based on the definition of the null hypothesis and divides the methods into competitive and self-contained (Goeman and Bühlmann 2007; Nam and Kim 2008). In this work, we focus on competitive methods, and in particular on the Fisher''s exact test, although the problems identified likely apply also for self-contained methods.Here we show that the results of all these methods are affected by crosstalk effects and that this phenomenon is related to the structure of the pathways. We propose the first approach that can (1) detect crosstalk when it exists, (2) quantify its magnitude, (3) correct for it, resulting in a more meaningful ranking among pathways in a specific biological condition, and (4) identify novel functional modules that can play an independent role and have different functions than the pathway they are currently located on. This method is expected to allow a better understanding of individual experiment results, as well as a more refined definition of the existing signaling pathways for specific phenotypes.     

A prospective,iterative, adaptive trial of carfilzomib‐based desensitization

Proteasome inhibitor–based strategies hold promise in transplant but have yielded varying results. Carfilzomib, a second‐generation proteasome inhibitor, may possess advantages over bortezomib, the first‐generation proteasome inhibitors. The purpose of this study was to evaluate the safety, toxicity, and preliminary efficacy of carfilzomib in highly HLA‐sensitized kidney transplant candidates. Renal transplant candidates received escalating doses of carfilzomib followed by plasmapheresis (group A) or an identical regimen with additional plasmapheresis once weekly before carfilzomib dosing. Thirteen participants received carfilzomib, which was well tolerated with most adverse events classified as low grade. The safety profile was similar to bortezomib desensitization; however, neurotoxicity was not observed with carfilzomib. Toxicity resulted in permanent dose reduction in 1 participant but caused no withdrawals or deaths. HLA antibodies were substantially reduced with carfilzomib alone, and median maximal immunodominant antibody reduction was 72.8% (69.8% for group A, P = .031, 80.1% for group B, P = .938). After depletion, rebound occurred rapidly and antibody levels returned to baseline between days 81 and 141. Bone marrow studies revealed that approximately 69.2% of plasma cells were depleted after carfilzomib monotherapy. Carfilzomib monotherapy–based desensitization provides an acceptable safety and toxicity profile while leading to significant bone marrow plasma cell depletion and anti‐HLA antibody reduction.     

Fiber-Templated 3D Calcium-Phosphate Scaffolds for Biomedical Applications: The Role of the Thermal Treatment Ambient on Physico-Chemical Properties

A successful bone-graft-controlled healing entails the development of novel products with tunable compositional and architectural features and mechanical performances and is, thereby, able to accommodate fast bone in-growth and remodeling. To this effect, graphene nanoplatelets and Luffa-fibers were chosen as mechanical reinforcement phase and sacrificial template, respectively, and incorporated into a hydroxyapatite and brushite matrix derived by marble conversion with the help of a reproducible technology. The bio-products, framed by a one-stage-addition polymer-free fabrication route, were thoroughly physico-chemically investigated (by XRD, FTIR spectroscopy, SEM, and nano-computed tomography analysis, as well as surface energy measurements and mechanical performance assessments) after sintering in air or nitrogen ambient. The experiments exposed that the coupling of a nitrogen ambient with the graphene admixing triggers, in both compact and porous samples, important structural (i.e., decomposition of β-Ca₃(PO₄)₂ into α-Ca₃(PO₄)₂ and α-Ca₂P₂O₇) and morphological modifications. Certain restrictions and benefits were outlined with respect to the spatial porosity and global mechanical features of the derived bone scaffolds. Specifically, in nitrogen ambient, the graphene amount should be set to a maximum 0.25 wt.% in the case of compact products, while for the porous ones, significantly augmented compressive strengths were revealed at all graphene amounts. The sintering ambient or the graphene addition did not interfere with the Luffa ability to generate 3D-channels-arrays at high temperatures. It can be concluded that both Luffa and graphene agents act as adjuvants under nitrogen ambient, and that their incorporation-ratio can be modulated to favorably fit certain foreseeable biomedical applications.     

喉罩麻醉采用靶控输注丙泊酚复合瑞芬太尼的临床效果分析

目的应用靶控输注丙泊酚与瑞芬太尼方式对接受手术治疗的患者实施喉罩麻醉的临床效果进行研究。方法将我院收治的88例接受手术治疗的患者随机分为对照组和观察组,分别给予靶控输注丙泊酚方式和靶控输注丙泊酚与瑞芬太尼方式实施喉罩麻醉。结果观察组患者手术麻醉效果明显优于对照组。结论应用靶控输注丙泊酚与瑞芬太尼方式对接受手术治疗的患者实施喉罩麻醉的临床效果非常明显。     

ACL Injury prevention in female athletes: review of the literature and practical considerations in implementing an ACL prevention program

Female athletes are at 3.5 times risk of sustaining a non-contact ACL injury compared with males. Research has shown that this gender discrepancy results from differences in neuromuscular adaptations and biomechanics related to landing techniques. Studies have examined the preventative effect of ACL prevention programs, which have been designed to address these risky neuromuscular and biomechanical patterns. We review the key studies on ACL prevention in female athletes and summarize the critical components of ACL prevention strategies that have been shown to successfully decrease ACL injury risk. We also discuss recommendations and practical considerations in the implementation of ACL prevention programs in various community settings.     

Early outcomes in human lung transplantation with Thymoglobulin or Campath-1H for recipient pretreatment followed by posttransplant tacrolimus near-monotherapy

OBJECTIVES: Acute and chronic rejection remain unresolved problems after lung transplantation, despite heavy multidrug immunosuppression. In turn, the strong immunosuppression has been responsible for mortality and pervasive morbidity. It also has been postulated to interdict potential mechanisms of alloengraftment. METHODS: In 48 lung recipients we applied 2 therapeutic principles: (1) recipient pretreatment with antilymphoid antibody preparations (Thymoglobulin [SangStat, Fremont, Calif] or Campath [alemtuzumab; manufactured by ILEX Pharmaceuticals, LP, San Antonio, Tex; distributed by Berlex Laboratories, Richmond, Calif]) and (2) minimal posttransplant immunosuppression with tacrolimus monotherapy or near-monotherapy. Our principal analysis was of the events during the critical first 6 posttransplant months of highest immunologic and infectious disease risk. Results were compared with those of 28 historical lung recipients treated with daclizumab induction and triple immunosuppression (tacrolimus-prednisone-azathioprine). RESULTS: Recipient pretreatment with both antilymphoid preparations allowed the use of postoperative tacrolimus monotherapy with prevention or control of acute rejection. Freedom from rejection was significantly greater with Campath than with Thymoglobulin (P = .03) or daclizumab (P = .05). After lymphoid depletion with Thymoglobulin or Campath, patient and graft survival at 6 months was 90% or greater. Patient and graft survival after 9 to 24 months is 84.2% in the Thymoglobulin cohort, and after 10 to 12 months, it is 90% in the Campath cohort. There has been a subjective improvement in quality of life relative to our historical experience. CONCLUSION: Our results suggest that improvements in lung transplantation can be accomplished by altering the timing, dosage, and approach to immunosuppression in ways that might allow natural mechanisms of alloengraftment and diminish the magnitude of required maintenance immunosuppression.     

Serum analysis after transplant nephrectomy reveals restricted antibody specificity patterns against structurally defined HLA class I mismatches

This study deals with HLA-mismatched kidney transplants that have been removed following rejection. Sera from 27 patients were screened for HLA-specific antibodies by direct complement-dependent lymphocytotoxicity with HLA-typed cell panels. Circulating donor-specific antibodies were detected in 3 cases (11%) before and in 26 cases (97%) after allograft nephrectomy. These findings demonstrate the production of donor-specific antibodies in patients with rejected transplants, but in most cases, they were undetectable before nephrectomy, because the graft had adsorbed them. With an HLAMatchmaker-based serum analysis program, we observed restricted antibody specificity patterns against amino acid triplet-defined epitopes on donor HLA-A,B antigens. Many donor triplets were non-reactive while others were apparently recognized by antibodies. In some patients, the donor triplet specific antibodies persisted for a long time whereas in many other patients, they became undetectable after a few months. The characterization of the antibody specificity profiles of post-allograft nephrectomy sera is clinically useful in defining criteria of HLA mismatch acceptability for sensitized patients awaiting another transplant. It provides also opportunities for determining the relative immunogenicity of mismatched triplets.