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This paper offers an insight into the approach utilised by two Clinical Psychologists in the NHS Lanarkshire Psychological Therapies for Older People team, in their attempt to understand, and respond to, resident and staff wellbeing within the complex care home system during the pandemic. We highlight relevant staff wellbeing literature with a focus on those in health and social care. We then describe our approach which has been informed by various theories, such as compassionate leadership, organisational change, and psychological safety. We define our ideas for improving staff and resident wellbeing at a systems level, framed in psychological theory and quality improvement goals. We offer our reflections throughout, which we hope will be useful to others working in similar complex systems.

This chapter covers the key physical, biological and practical challenges encountered when developing cryopreservation protocols for larger biological structures and examines areas where cryopreservation has been successful in scaling to larger structures. Results from techniques being used in attempts to overcome these challenges are reviewed together with the indicators for future development that arise from them. The scale-up of cryopreservation to tissues with diverse functions and cell types makes the control of freezing and thawing more challenging. Technology may—or may not—be available depending on the size of the material involved. To meet the challenge there must be innovation in technology, techniques and understanding of damage-limiting strategies. Diversity of cell structure, size, shape and expected function means a similarly diverse response to any imposed cryopreservation conditions and interaction with ice crystals. The increasing diffusion distances involved, and diversity of permeability properties, will affect solutes, solvents, heat and cryoprotectant (CPA) transfer and so add to the diversity of response. Constructing a single protocol for cryopreservation of a larger sample (organoids to whole organs) becomes a formidable challenge.

Cytosine deaminases AID/APOBEC proteins act as potent nucleic acid editors, playing important roles in innate and adaptive immunity. However, the mutagenic effects of some of these proteins compromise genomic integrity and may promote tumorigenesis. Here, we demonstrate that human APOBEC3G (A3G), in addition to its role in innate immunity, promotes repair of double-strand breaks (DSBs) in vitro and in vivo. Transgenic mice expressing A3G successfully survived lethal irradiation, whereas wild-type controls quickly succumbed to radiation syndrome. Mass spectrometric analyses identified the differential upregulation of a plethora of proteins involved in DSB repair pathways in A3G-expressing cells early following irradiation to facilitate repair. Importantly, we find that A3G not only accelerates DSB repair but also promotes deamination-dependent error-free rejoining. These findings have two implications: (a) strategies aimed at inhibiting A3G may improve the efficacy of genotoxic therapies used to cure malignant tumours; and (b) enhancing A3G activity may reduce acute radiation syndrome in individuals exposed to ionizing radiation.

ObjectiveDelivering person-centered care in individuals with knee osteoarthritis (OA) necessitates consideration of other chronic conditions that frequently co-occur. We sought to understand the extent to which arthritis therapists consider type 2 diabetes mellitus (T2DM) when treating persons with knee OA and concomitant T2DM, and barriers to doing so.MethodsWe conducted 18 semistructured telephone interviews with arthritis therapists working within a provincially funded arthritis care program (Arthritis Society Canada) in Ontario, Canada. We first analyzed interviews deductively using the Theoretical Domains Framework (TDF) to comprehensively identify barriers and enablers to health behaviors. Then, within TDF domains, we inductively developed themes.ResultsWe identified 5 TDF domains as prominently influencing the behavior of arthritis therapists considering concomitant T2DM when developing a knee OA management plan. These were as follows: therapists’ perceived lack of specific knowledge around comorbidities including diabetes; the lack of breadth in skills in behavioral change techniques to help patients set and reach their goals, particularly when it came to physical activity; variable intention to factor a patient’s comorbidity profile to influence their treatment recommendations; the perception of their professional role and identity as joint focused; and the environmental context with lack of formalized follow-up structure of the current Arthritis Society Canada program that limited sufficient patient monitoring and follow-up.ConclusionWithin the context of a Canadian arthritis program, we identified several barriers to arthritis therapists considering T2DM in their management plan for persons with knee OA and T2DM. These results can help inform strategies to improve person-centered OA care and overall health outcomes.

Epithelial barrier tissues such as the skin and airway form an essential interface between the mammalian host and its external environment. These physical barriers are crucial to prevent damage and disease from environmental insults and allergens. Failure to maintain barrier function against such risks can lead to severe inflammatory disorders, including atopic dermatitis and asthma. Here, we discuss the role of the morphogen Sonic Hedgehog in postnatal skin and lung and the impact of Shh signalling on repair, inflammation, and atopic disease in these tissues., Our research is funded by the MRC (MR/S037764/1 and MR/P00084/1) and BBSRC (BB/T020970/1).

Allergic asthma is a common inflammatory airway disease in which Th2 immune response and inflammation are thought to be triggered by inhalation of environmental allergens. Many studies using mouse models and human tissues and genome-wide association have indicated that Sonic Hedgehog (Shh) and the Hedgehog (Hh) signaling pathway are involved in allergic asthma and that Shh is upregulated in the lung on disease induction. We used a papain-induced mouse model of allergic airway inflammation to investigate the impact of systemic pharmacological inhibition of the Hh signal transduction molecule smoothened on allergic airway disease induction and severity. Smoothened-inhibitor treatment reduced the induction of Shh, IL-4, and IL-13 in the lung and decreased serum IgE, as well as the expression of Smo, Il4, Il13, and the mucin gene Muc5ac in lung tissue. Smoothened inhibitor treatment reduced cellular infiltration of eosinophils, mast cells, basophils, and CD4+ T-cells to the lung, and eosinophils and CD4+ T-cells in the bronchoalveolar lavage. In the mediastinal lymph nodes, smoothened inhibitor treatment reduced the number of CD4+ T-cells, and the cell surface expression of Th2 markers ST2 and IL-4rα and expression of Th2 cytokines. Thus, overall pharmacological smoothened inhibition attenuated T-cell infiltration to the lung and Th2 function and reduced disease severity and inflammation in the airway.

T cell acute lymphoblastic leukemia (T-ALL) is an aggressive malignancy of immature T lymphocytes, associated with higher rates of induction failure compared with those in B cell acute lymphoblastic leukemia. The potent immunotherapeutic approaches applied in B cell acute lymphoblastic leukemia, which have revolutionized the treatment paradigm, have proven more challenging in T-ALL, largely due to a lack of target antigens expressed on malignant but not healthy T cells. Unlike B cell depletion, T-cell aplasia is highly toxic. Here, we show that the chemokine receptor CCR9 is expressed in >70% of cases of T-ALL, including >85% of relapsed/refractory disease, and only on a small fraction (

Summary Interferon‐inducible transmembrane (IFITM) proteins are a family of small homologous proteins, localized in the plasma and endolysosomal membranes, which confer cellular resistance to many viruses. In addition, several distinct functions have been associated with different IFITM family members, including germ cell specification (IFITM1–IFITM3), osteoblast function and bone mineralization (IFITM5) and immune functions (IFITM1–3, IFITM6). IFITM1–3 are expressed by T cells and recent experiments have shown that the IFITM proteins are directly involved in adaptive immunity and that they regulate CD4+ T helper cell differentiation in a T‐cell‐intrinsic manner. Here we review the role of the IFITM proteins in T‐cell differentiation and function., Recent studies have identified new T‐cell‐intrinsic roles for the IFITM family in T helper differentiation and atopic and inflammatory disease, which are independent of their functions in cellular resistance to viral infection.

Overall, the Saving Mothers, Giving Life partnership was praised as a successful model for interagency coordination. Key strengths included diversity in partner expertise, high-quality monitoring and evaluation, strong leadership, and country ownership. Uncertainty about partner roles and responsibilities, perceived power inequities between partners, bureaucratic processes, and limited Ministry of Health representation in the governance structure were some challenges that, if addressed by similar public-private partnerships under development, may improve long-term partnership success., Background: Public-private partnerships (PPPs) have garnered appeal among governments around the world, making impressive contributions to health resource mobilization and improved health outcomes. Saving Mothers, Giving Life (SMGL), a PPP aimed at reducing maternal deaths, was born out of the need to mobilize new actors, capitalize on diverse strengths, and marshal additional resources. A qualitative study was initiated to examine how the SMGL partnership functioned to achieve mortality reduction goals and foster country ownership and sustainability. Methods: We purposively selected 57 individuals from U.S. and global public and private partner organizations engaged in SMGL in Uganda and Zambia for qualitative in-depth interviews. Representative selection was based on participant knowledge of partner activities and engagement with the partnership at various points in time. Of those invited, 46 agreed to participate. Transcripts were double-coded, and discordant codes were resolved by consensus. Results: Several recurring themes emerged from our study. Perceived strengths of the partnership included goal alignment; diversity in partner expertise; high-quality monitoring, evaluation, and learning; and strong leadership and country ownership. These strengths helped SMGL achieve its goals in reducing maternal and newborn mortality. However, uncertainty in roles and responsibilities, perceived power inequities between partners, bureaucratic processes, a compressed timeline, and limited representation from ministries of health in the SMGL governance structure were reported impediments. Conclusion: While SMGL faced many of the same challenges experienced by other PPPs, local counterparts and the SMGL partners were able to address many of these issues and the partnership was ultimately praised for being a successful model of interagency coordination. Efforts to facilitate country ownership and short-term financial sustainability have been put in place for many elements of the SMGL approach; however, long-term financing is still a challenge for SMGL as well as other global health PPPs. Addressing key impediments outlined in this study may improve long-term sustainability of similar PPPs.

During positive selection at the transition from CD4+CD8+ double-positive (DP) to single-positive (SP) thymocyte, TCR signalling results in appropriate MHC restriction and signals for survival and progression. We show that the pioneer transcription factors Foxa1 and Foxa2 are required to regulate RNA splicing during positive selection of mouse T cells and that Foxa1 and Foxa2 have overlapping/compensatory roles. Conditional deletion of both Foxa1 and Foxa2 from DP thymocytes reduced positive selection and development of CD4SP, CD8SP and peripheral naïve CD4+ T cells. Foxa1 and Foxa2 regulated the expression of many genes encoding splicing factors and regulators, including Mbnl1, H1f0, Sf3b1, Hnrnpa1, Rnpc3, Prpf4b, Prpf40b and Snrpd3. Within the positively selecting CD69+DP cells, alternative RNA splicing was dysregulated in the double Foxa1/Foxa2 conditional knockout, leading to >850 differentially used exons. Many genes important for this stage of T-cell development (Ikzf1-3, Ptprc, Stat5a, Stat5b, Cd28, Tcf7) and splicing factors (Hnrnpab, Hnrnpa2b1, Hnrnpu, Hnrnpul1, Prpf8) showed multiple differentially used exons. Thus, Foxa1 and Foxa2 are required during positive selection to regulate alternative splicing of genes essential for T-cell development, and, by also regulating splicing of splicing factors, they exert widespread control of alternative splicing., Summary: The pioneer transcription factors Foxa1 and Foxa2 are required for positive selection during T-cell development in the thymus for regulation of RNA splicing.

Paediatric heart transplantation recipients suffer an increased incidence of infectious, autoimmune and allergic problems. The relative roles of thymus excision and immunosuppressive treatments in contributing to these sequelae are not clear. We compared the immunological phenotypes of 25 heart transplant recipients (Tx), 10 children who underwent thymus excision during non-transplantation cardiac surgery (TE) and 25 age range-matched controls, in two age bands: 1-9 and 10-16 years. Significant differences from controls were seen mainly in the younger age band with Tx showing lower CD3 and CD4 cell counts whilst TE showed lower CD8 cell counts. Naïve T cell and recent thymic emigrant proportions and counts were significantly lower than controls in both groups in the lower age band. T cell recombination excision circle (TREC) levels were lower than controls in both groups in both age bands. There were no differences in regulatory T cells, but in those undergoing thymus excision in infancy, their proportions were higher in TE than Tx, a possible direct effect of immunosuppression. T cell receptor V beta spectratyping showed fewer peaks in both groups than in controls (predominantly in the older age band). Thymus excision in infancy was associated with lower CD8 cell counts and higher proportions of Tregs in TE compared to Tx. These data are consistent with thymus excision, particularly in infancy, being the most important influence on immunological phenotype after heart transplantation.

Pre-T-cell receptor (TCR) signal transduction is required for developing thymocytes to differentiate from CD4

Pre-TCR signal transduction is required for developing thymocytes to differentiate from CD4-CD8- double negative (DN) to CD4+CD8+ double positive (DP) cell. Notch signalling is required for T-cell fate specification and must be maintained throughout β-selection, but inappropriate Notch activation in DN4 and DP cells is oncogenic. Here, we show that pre-TCR signalling leads to increased expression of the transcriptional repressor Bcl6 and that Bcl6 is required for differentiation to DP. Conditional deletion of Bcl6 from thymocytes reduced pre-TCR-induced differentiation to DP cell, disrupted expansion and enrichment of icTCRβ+ cells within the DN population and increased DN4 cell death. It also increased Notch1 activation and Notch-mediated transcription in the DP population. Thus, Bcl6 is required in thymocyte development for efficient differentiation from DN3 to DP cell and to attenuate Notch1 activation in DP cells. Given the importance of inappropriate NOTCH1 signalling in T-ALL, and the involvement of Bcl6 in other types of leukaemia, this study is important to our understanding of T-ALL.

The Kepler spacecraft revolutionized the field of exoplanet discovery during its prime mission and expanded upon that with its K2 extended mission following the failure of a second reaction wheel. While the K2 mission demonstrated that the Kepler spacecraft was still able to perform high-resolution photometry and find exoplanets, there were still many challenges to be faced from aging hardware, the increasing distance from the Earth and the desire to make the mission last as long as possible. This paper, which derives material from a paper the authors delivered at the SpaceOps 2018 conference [1], will review several examples of these challenges, the solutions that were devised and their outcomes with regard to improving performance, extending the mission lifetime, and demonstrating the cost-effectiveness of a small mission operations team.

Transformation and heroism are reciprocally related. Transformation produces an individual that others may call hero; one who inspires, guides, and protects something precious—an ordinary extraordinary person, master of the self. Heroes exhibit the further reaches of human development by transforming into entirely new, resplendent individuals that demonstrate valuable capacities whiles still being mortal. Because transformation is the means through which heroes are made, a more thorough understanding of the forces affecting transformation may advance collective understanding of the demands upon the individual. Founded on the scholarship of seminal authors of depth psychology, East Indian spirituality, anthropology, physics, mythology, Hermetic science, and other disciplines, this paper argues that a hero develops through both natural and supernatural processes, which can eventually produce a transhuman or superhero—depending on one's perspective, one who is natural (bound by nature) and supernatural (beyond nature). If this psychospiritual proposition has merit, advancement from ordinary to hero and from hero to super hero—each resulting from trans-form-ation—constitutes a subtle yet fundamental change in form, a microevolution of a subsect of individuals. The progressive framework begins with a description of patterns of evolution salient to heroism and transformation; an exploration of four key “laws” that govern the realm of matter, which support and delimit the budding hero as an earth-bound human; and an examination of four “supernatural” abilities the initiate must cultivate and enact in order to transform. The heart of the paper is a detailed guide identifying when during the process of transformation, the initiate can expect to receive the support of natural processes, when to be vigilant for beyond nature or Divine intervention, and when to intervene with “supernatural” activities. The framework culminates with an elucidation of how the ordinary yet heroic individual becomes a superhero or transhuman as outlined by spiritual teacher Sri Aurobindo, through three transformations of biopsychosocial maturation and spiritual realization.

BACKGROUND: Electronic diabetes registers promote structured care and enable identification of undiagnosed diabetes, but they require consistent coding of the diagnosis in electronic medical records. We investigated the potential of electronic medical records to identify undiagnosed diabetes and to support diabetes management in a large primary care population in the United States. METHODS: We conducted a cross-sectional study and retrospective observational cohort analysis of primary care electronic medical records from a nationally representative US database (GE Centricity). We tested the feasibility of identifying patients with undiagnosed diabetes by applying simple algorithms to the electronic medical record data. We compared the quality of care provided to patients in the United States who had diabetes (coded and uncoded) for at least 15 months with the quality of care provided in England using a set of 16 indicators. RESULTS: We included 11 540 454 electronic medical records from more than 9000 primary care clinics across the United States. Of the 1 110 398 records indicating diagnosed diabetes, only 61.9% contained a diagnostic code. Of the 10 430 056 records for nondiabetic patients, 0.4% (n = 40 359) had at least 2 abnormal fasting or random blood glucose values, and 0.2% (n = 23 261) of the remaining records had at least 1 documented glycated hemoglobin (HbA1c) value of 6.5% or higher. Among the 622 260 patients for whom information on quality-of-care indicators was available, those with a coded diagnosis of diabetes had a significantly higher level of quality of care than those with uncoded diabetes (p < 0.01); however, the quality of care was generally lower than that indicated in England. INTERPRETATION: We were able to identify a substantial number of patients with uncoded diabetes and probable undiagnosed diabetes using simple algorithms applied to the primary care electronic records. Electronic coding of the diagnosis was associated with improved quality of care. Electronic diabetes registers are underused in US primary care and provide opportunities to facilitate the systematic, structured approach that is established in England.

Solanki et al. show that stromal activity of the transcription factor Gli3 is required for B cell development in the fetal liver. Gli3 functions to repress Shh expression, and Shh signals to developing B cells to regulate their development at multiple developmental stages., Before birth, B cells develop in the fetal liver (FL). In this study, we show that Gli3 activity in the FL stroma is required for B cell development. In the Gli3-deficient FL, B cell development was reduced at multiple stages, whereas the Sonic hedgehog (Hh [Shh])–deficient FL showed increased B cell development, and Gli3 functioned to repress Shh transcription. Use of a transgenic Hh-reporter mouse showed that Shh signals directly to developing B cells and that Hh pathway activation was increased in developing B cells from Gli3-deficient FLs. RNA sequencing confirmed that Hh-mediated transcription is increased in B-lineage cells from Gli3-deficient FL and showed that these cells expressed reduced levels of B-lineage transcription factors and B cell receptor (BCR)/pre-BCR–signaling genes. Expression of the master regulators of B cell development Ebf1 and Pax5 was reduced in developing B cells from Gli3-deficient FL but increased in Shh-deficient FL, and in vitro Shh treatment or neutralization reduced or increased their expression, respectively.

Objectives The purpose of this study was to determine whether cancer can be attributed to statin use among a general population of older adults in the United States with at least 3 years of follow-up. Background Statins are widely prescribed drugs in the United States for the management of dyslipidemia, atherosclerosis, and cardiovascular event risk reduction. Unsettled scientific debate about the association of statins with cancer continues, with high-profile studies showing conflicting results. Methods A retrospective cohort analysis of the incidence of cancer in older adults who have and who have not used statins was performed. More than 11 million analyzable patient records from January 1990 through February 2009 were drawn from the General Electric Centricity electronic medical records database. Propensity matching found pairs of patients receiving and not receiving statin therapy who shared similar propensities for statin use. Results Propensity score methods matched 45,857 comparison pairs of patients taking a statin and patients not taking a statin. The average time in the database was 8 years, with pairs being followed for an average of 4.6 and 4.7 years. After matching, the incidence of cancer in patients taking a statin was 11.37% compared with 11.11% in matched patients not taking a statin. Multivariate-matched Cox regression analysis showed a nonsignificant hazard ratio of 1.04 (95% confidence interval: 0.99 to 1.09). Kaplan-Meier curves for diagnosis of any cancer up to 10 years also showed no difference for patients taking a statin and those not taking a statin. Conclusions This retrospective analysis of nearly 46,000 propensity-matched pairs demonstrated no statistically significant increased risk of cancer associated with statins.

Objectives Therapy for osteoporosis reduces the risk of fracture in clinical trials; real-world adherence to therapy is suboptimal and may reduce the effectiveness of intervention. The objective was to assess the fracture risk among patients nonadherent versus adherent to therapy for osteoporosis. Methods Medline, Embase, and CINAHL were searched for English-language publications of observational studies (January 1998–February 2009). Proceedings from two recent meetings of five relevant conferences were hand searched. Prospective and retrospective observational studies of patients with osteoporosis receiving bisphosphonates, parathyroid hormone, or selective estrogen receptor modulators denosumab were included. Studies were required to consider both fracture risk and adherence (compliance and/or persistence); any definition of adherence/fracture was acceptable. Data were analyzed using pooled comparisons of the odds and hazard ratios of fracture in noncompliance versus compliance and nonpersistence versus persistence. Sensitivity analyses were conducted to determine the effect of clinical heterogeneity on the results. Results Twenty-seven citations were identified, the majority of which were retrospective database analyses considering the effect of adherence to bisphosphonate therapy on fracture at any skeletal site. The absolute frequency of fracture ranged from 6% to 38% with noncompliance and from 5% to 19% with nonpersistence (104–159 weeks). Meta-analysis indicates that fracture risk increases by approximately 30% with noncompliance (odds ratio [95% confidence interval] 1.29 [1.22–1.38]; hazard ratio 1.28 [1.18–1.38]) and by 30% to 40% with nonpersistence (odds ratio 1.40 [1.29–1.52]; hazard ratio 1.32 [1.23–1.42]). Conclusions Poor medication adherence is associated with a significantly increased risk of fracture versus optimal adherence. Improving medication adherence in patients with osteoporosis may lead to a greater reduction in fracture.

Relatively little is understood regarding the aetiology of bipolar disorder (BD) other than for the influence of a large genetic component on the development of the disorder and the impact of stressful life events on changes in current mood. However, amongst a range of psychiatric diagnoses, research consistently demonstrates a higher frequency of reports of childhood abuse and neglect compared with individuals in the general population. In addition, those who report experiences of childhood maltreatment also report high levels of internalized shame in adulthood, although there is little research demonstrating this association amongst clinical populations. An adult sample of 35 participants with a diagnosis of BD and a control group of 35 participants with no psychiatric diagnoses completed measures of childhood abuse and neglect, and internalized shame. Participants in the BD group reported a significantly greater frequency of high levels of childhood trauma compared with participants in the control group, with the reported frequency of childhood emotional abuse and neglect being particularly high. Levels of current internalized shame were also significantly higher amongst participants in the BD group. Significant correlations were observed between current internalized shame and reports of childhood emotional abuse and neglect. Clinical implications of the study's findings are discussed, and limitations of the methodology are considered. Copyright © 2011 John Wiley & Sons, Ltd. Key Practitioner Message The frequency of reports of childhood trauma would appear to be higher amongst adults with a diagnosis of BD compared with individuals with no psychiatric diagnoses. Levels of internalized shame in adulthood are also likely to be higher than those in the general population, although the current literature does not shed light on the relationship between childhood abuse and neglect, mood-related behaviour, and shame. Experiences of childhood abuse and neglect, particularly childhood emotional abuse and emotional neglect, are likely to be frequently reported by clients with a diagnosis of BD. Clinicians should therefore explicitly consider these experiences in their assessment, formulation and intervention with clients with a diagnosis of BD.

The aim of the study was to explore experiences of practising mindfulness and how this related to living with, and managing, bipolar disorder. Qualitative methodology was used to explore the experiences of 12 people with bipolar disorder who had been practising mindfulness for at least 18 weeks. Semi-structured interviews exploring how mindfulness practice related to living with bipolar disorder were recorded verbatim, transcribed and analysed using thematic analysis. Seven themes emerged: Focusing on what is present; clearer awareness of mood state/change; acceptance; mindfulness practice in different mood states; reducing/stabilizing negative affect; relating differently to negative thoughts; reducing impact of mood state. All participants reported subjective benefits and challenges of mindfulness practice, and gave insights into processes of change.

What do the terms Learning Healthcare Systems, Participatory Medicine, Evidence-based Medicine, Narrative Medicine, Patient-centered Medicine, and Health 2.0 mean? What is their connection to each other, to User-Driven Healthcare, and, most importantly, to real people—healthcare providers and healthcare consumers? In this paper, the author presents current definitions of these abstractions to begin to compile a glossary of terms, a lexicon of sorts, for all stakeholders in the emerging field of User-Driven Healthcare.

Objective: To compare clinical and economic outcomes (hospital costs) in women undergoing laparoscopic hysterectomy performed with and without robotic assistance in inpatient and outpatient settings. Methods: Using the Premier hospital database, we identified women .18 years of age with a record of minimally invasive hysterectomy performed in 2007 to 2008. Univariable and multivariable analyses examined the association between robot- assisted hysterectomy and adverse events, hospital costs, surgery time, and length of stay. Results: Of 36188 patient records analyzed from 358 hospitals, 95% (n 5 34527) of laparoscopic hysterectomies were per- formed withoutrobotic assistance. Inpatientand outpatient settingsdid notdiffer substantivelyin frequencyof adverseevents. For cardiac, neurologic, wound, and vascular complications, frequencies were ,1% for robot and non-robot procedures. In inpatient and outpatient settings alike, use of robotic assistance was consistently associated with statistically significant, higher per-patient average hospital costs. Inpatient procedures with and without robotic assistance cost $9640 (95% confi- dence interval (CI) 5 $9621, $9659) versus $6973 (95% CI 5 $6959, $6987), respectively. Outpatient procedures with and without robotic assistance cost $7920 (95% CI 5 $7898, $7942) versus $5949 (95% CI 5 $5932, $5966), respectively. Inpatient surgery times were significantly longer for robot-assisted procedures, 3.22 hours (95% CI 5 3.21, 3.23) compared with non-robot procedures at 2.82 hours (95% CI 5 2.81, 2.83). Similarly, outpatient surgery times with robot averaged 2.99 hours (95% CI 5 2.98, 3.00) versus 2.46 hours (2.45, 2.47) for non-robot procedures. Conclusion: Our findings reveal little clinical differences in perioperative and postoperative events. This, coupled with the increased per-case hospital cost of the robot,suggests that further investigation is warranted when considering this technology for routine laparoscopic hysterectomies. Journal of Minimally Invasive Gynecology (2010) 17, 730-738 2010 AAGL. All rights reserved.

OBJECTIVE: The aim of this study was to determine the effects of repeated courses of prenatal corticosteroid therapy versus placebo on death or neurologic impairment among the children enrolled in the Multiple Courses of Antenatal Corticosteroids for Preterm Birth Study, at 18 to 24 months of age. METHODS: A total of 2305 infants were eligible for follow-up evaluation; 2104 infants (1069 in the prenatal corticosteroid therapy group and 1035 in the placebo group) were monitored. The primary outcome was death or neurologic impairment, defined as either cerebral palsy or cognitive delay, at 18 to 24 months of age. The secondary outcomes were measurements of growth (height, weight, and head circumference). RESULTS: Children exposed to multiple courses of prenatal corticosteroid therapy had similar rates of death or neurologic impairment, compared with children exposed to placebo (148 children [13.8%] vs 142 children [13.7%]; odds ratio: 1.001[95% confidence interval: 0.75–1.30]; P = .95). They had a mean weight of 11.94 kg, compared with 12.14 kg in the placebo group (P = .04), a mean height of 85.51 cm, compared with 85.46 cm (P = .87), and a mean head circumference of 48.18 cm, compared with 48.25 cm (P = .45). CONCLUSIONS: Multiple courses of prenatal corticosteroid therapy, given every 14 days, did not increase or decrease the risk of death or neurologic impairment at 18 to 24 months of age, compared with a single course of prenatal corticosteroid therapy. Continued follow-up monitoring of these children is necessary to assess neurobehavioral function, school performance, and possible susceptibility to disease.

The Hedgehog (Hh) signaling pathway influences multiple stages of murine T-cell development. Hh signaling mediates transcriptional changes by the activity of the Gli family of transcription factors, Gli1, Gli2 and Gli3. Both Gli2 and Gli3 are essential for mouse development and can be processed to function as transcriptional repressors or transcriptional activators, whereas Gli1, itself a transcriptional target of Hh pathway activation, can only function as a transcriptional activator and is not essential for mouse development. Gli1-deficient mice are healthy and appear normal and nonredundant functions for Gli1 have been difficult to identify. Here we show that Gli1 is non-redundant in the regulation of T-cell development in the thymus, at multiple developmental stages. Analysis of Gli1-deficient embryonic mouse thymus shows a role for Gli1 to promote the differentiation of CD4⁻CD8⁻ double negative (DN) thymocytes before pre- TCR signal transduction, and a negative regulatory function after pre-TCR signaling. In addition, introduction of a Class I-restricted transgenic TCR into the adult Gli1-deficient and embryonic Gli2-deficient thymus showed that both Gli1 and Gli2 influence its selection to the CD8 lineage.