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Functionalized lipid probes are a critical new tool to interrogate the function of individual lipid species, but the structural parameters that constrain their utility have not been thoroughly described. Here, we synthesize three palmitic acid derivatives with a diazirine at different positions on the acyl chain and examine their metabolism, subcellular localization, and protein interactions. We demonstrate that while they produce very similar metabolites and subcellular distributions, probes with the diazirine at either end pulldown distinct subsets of proteins after photo-crosslinking. This highlights the importance of thoughtful diazirine placement when developing probes based on biological molecules. [ABSTRACT FROM AUTHOR]

The article focuses on questioning the necessity of stone analysis and 24-hour urine testing in managing renal stone disease. Topics include the limitations of 24-hour urine analysis, such as variability in results and patient inconvenience, the challenges of conducting reliable stone composition analysis, and the argument for using empiric treatment over routine testing for most kidney stone patients.

Over the past few decades, there have been increasing global efforts to limit or ban the use of animals for testing cosmetic products. This ambition has been at the heart of international endeavours to develop new in vitro and animal-free approaches for assessing the safety of cosmetics. While several of these new approach methodologies (NAMs) have been approved for assessing different toxicological endpoints in the UK and across the EU, there remains an absence of animal-free methods for screening for dermal absorption; a measure that assesses the degree to which chemical substances can become systemically available through contact with human skin. Here, we identify some of the major technical barriers that have impacted regulatory recognition of an in vitro skin model for this purpose and propose how these could be overcome on-chip using artificial cells engineered from the bottom-up. As part of our future perspective, we suggest how this could be realised using a digital biomanufacturing pipeline that connects the design, microfluidic generation and 3D printing of artificial cells into user-crafted synthetic tissues. We highlight milestone achievements towards this goal, identify future challenges, and suggest how the ability to engineer animal-free skin models could have significant long-term consequences for dermal absorption screening, as well as for other applications. [ABSTRACT FROM AUTHOR]

Polyacrylamide (PAM) is grafted from the surface of activated carbon (AC) by surface‐initiated activators generated by electron transfer atom transfer radical polymerization (SI‐AGET ATRP). This is accomplished by pre‐functionalizing the surface of activated carbon by oxidation, followed by the attachment of an ATRP initiator. From this surface, SI‐AGET ATRP of acrylamide monomers is performed. The resulting AC‐PAM is characterized by FTIR, XPS, TGA, and BET analysis. Additionally, the grafted polymer is cleaved from the surface of AC and its molecular weight distribution is measured by SEC. This material is designed to explore the effect that grafting a polymer flocculant onto AC will have on the polymer's flocculating abilities. This is evaluated by measuring the flocculation and dewatering of mature fine tailings (MFT) when dosed with the AC‐PAM compared to PAM. In all, this work demonstrates the successful grafting of PAM onto AC, as well as potential wastewater applications for this composite material. [ABSTRACT FROM AUTHOR]

Objectives: To investigate global changes in ureters at the transcriptional, translational and functional levels, both while stents are indwelling and after removal and recovery, and to study the effects of targeting pathways that play a potential role. Methods: Pig ureters were stented for varying amounts of time (48 h, 72 h, 14 days) and the impact on peristalsis, dilatation and hydronephrosis were assessed. RNAseq, proteomic, histological and smooth muscle (SM) function analyses were performed on ureteric and kidney tissues to assess changes induced by stenting and recovery. Pathway analysis was performed using Ingenuity Pathway Analysis software. To study the impact of possible interventions, the effects of erythropoeitin (EPO) and a Gli1 inhibitor were assessed. Results: Stenting triggers massive ureteric dilatation, aperistalsis and moderate hydronephrosis within 48 h. Pathways associated with obstruction, fibrosis and kidney injury were upregulated by stenting. Increased expression of GLI1, clusterin‐α (a kidney injury marker) and collagen 4A2 (a fibrosis marker) was found in stented vs contralateral unstented ureters. EPO did not improve peristalsis or contraction force but did decrease non‐purposeful spasming seen exclusively in stented ureters. Tamsulosin administration increased contractility but not rate of peristalsis in stented ureters. Conclusions: Ureters respond to stents similarly to how they respond to an obstruction, that is, with activation of pathways associated with hydronephrosis, fibrosis and kidney injury. This is driven by significant dilatation and associated ureteric SM dysfunction. EPO and tamsulosin induced mild favourable changes in SM physiology, suggesting that targeting specific pathways has potential to address stent‐induced complications. [ABSTRACT FROM AUTHOR]

Canine-assisted interventions have emerged as an increasingly popular means to engage and assist veterans coping with military-associated trauma responses. The present study evaluates the use of a 14-week service dog training program for these trauma-impacted veterans. The service dog program guides veterans in small group cohorts on how to train their own dog to be their personal service animal. All 71 veterans participating in this investigation had been diagnosed with PTSD. Fifty-five veterans (77%) finished the entire 14-week program and took all pretests and posttests. Compared to pretest scores, participants reported significant decreases in self-disturbance, posttraumatic stress, externalization, and somatization after completing the program. Participants experienced significant reductions in a broad scope of psychological impacts associated with their PTSD including interpersonal difficulties and suicidality. Findings provide evidence that service dog training programs may be an effective therapeutic alternative to traditional approaches that PTSD-impacted veterans are willing to utilize. [ABSTRACT FROM AUTHOR]

The author discusses the 1960s Black Arts Movement, its artists and their impact on contemporary arts as of 2023. Topics covered include the artists' challenge of prevailing cultural norms and encouragement of Black self-expression of their own experiences, and the pivotal roles of visual artists Wadsworth Jarrell and Jae Jarrell who respectively founded an artists' collective, and empowered fashion via the "Revolutionary Suit." Also noted is the movement's influence on artists like Nick Cave.

The medical and surgical management of kidney stones is one of the most common functions of the urologist. Management choices are often nuanced, involving the decision to embark on one surgical plan among several options. As the wider medical community critically evaluates the care we provide to an increasingly diverse population, it will be important to examine patient outcomes with a particular focus on ensuring equitable care. This review examines the influence of social parameters on the care of kidney stone patients. The dearth of literature in this area warrants rigorous studies on the relationship between race as well as socioeconomic status and the management of kidney stone disease. [ABSTRACT FROM AUTHOR]

Introduction: The novel coronavirus disease (COVID-19) pandemic has had a significant impact on the care of patients with urolithiasis. Recommendations and prioritization of endourologic surgical procedures vary among regions, and a comprehensive overall international directive is needed. We used the Delphi method to obtain international consensus on managing urolithiasis patients during the pandemic. Methods: A three-round Delphi process was used to elicit expert consensus (53 global key opinion leaders within the Endourological Society from 36 countries) on an extensive survey on management of endourologic patients in a pandemic. Questions addressed general management, inpatient and outpatient procedures, clinic visits, follow-up care, and best practices for suspension and resumption of routine care. Results: Consensus was achieved in 64/84 (76%) questions. Key consensus findings included the following: consultations should be delivered remotely when possible. Invasive surgical procedures for urolithiasis patients should be reserved for high-risk situations (infection, renal failure, etc.). To prevent aerosolization, spinal anesthesia is preferred over general, whenever feasible. Treatment of asymptomatic renal stones should be deferred. Primary definitive treatment of obstructing or symptomatic stones (both renal and ureteral) is preferred over temporizing drainage. Extracorporeal shockwave lithotripsy should be continued for obstructive ureteral stones. There was consensus on treatment modalities and drainage strategies depending on location and size of the stone. Conclusion: International endourologist members of the Endourological Society participated in this Delphi initiative to provide expert consensus on management of urolithiasis during a pandemic. These results can be applied currently and during a future pandemic. [ABSTRACT FROM AUTHOR]

The band gaps of three forms of polyaniline (PANI) are calculated using the DFT method with the B3LYP functional and SV(P) basis set. This marks the first time that the band gap for this polymer has been calculated using this DFT method. The calculations include an investigation of the effect of varying the benzoid–quinoid structural units, the effect of increasing oligomer length, and the inclusion of Michael's addition structures, which could be residual in the polymer depending on the chosen synthetic method. All results were compared with the experimentally determined band gap of 1.5 eV as typically reported in the literature. A commonly used structural motif of alternating benzoid–quinoid units and a ratio of 0.5:0.5 benzoid–quinoid resulted in a computed band gap of 1.9 eV. Inclusion of one extra quinoid unit gave rise to a band gap of 1.3 eV. Incorporation of a Michael's addition structure was found to dominate the band gap calculation, yielding a localized LUMO and a band gap of 1.3 eV that was insensitive to the polymer chain length and composition. [ABSTRACT FROM AUTHOR]

We present recently developed strategies to manipulate lipid levels in live cells by light. We focus on photoremovable protecting groups that lead to subcellular restricted localization and activation and discuss alternative techniques. We emphasize the development of organelle targeting of caged lipids and discuss recent advances in chromatic orthogonality of caging groups for future applications. [ABSTRACT FROM AUTHOR]

This article describes the findings of a qualitative investigation that provide some of the first detailed information from the caregiver's perspective about utilizing hippotherapy for children with a wide range of needs. In contrast to prior studies that focused primarily on the benefits of hippotherapy for children with cerebral palsy (CP) and autism spectrum disorder (ASD), this study included children with a broader range of congenital disorders, developmental disabilities, and medical issues. Many research studies have looked at the benefits of hippotherapy for those with CP and ASD. There is limited research on the impact of this form of therapy on various other childhood diseases or disorders. This multiple case study identified patterns of caregivers' responses to semi-structured interview questions as to the impact of hippotherapy on their children. Semi-structured interviews were completed with 11 caregivers. Thematic analysis of the qualitative interviews identified four themes; caregiver life concerns for their children, benefits of hippotherapy, quality of life improvements, and use of other therapies. The findings of this study represent a valuable first step in gaining a better understanding of the benefits of hippotherapy for these children. They are consistent with and expand upon findings of earlier studies that found therapeutic benefits for children with ASD and CP who participated in hippotherapy. [ABSTRACT FROM AUTHOR]

Study Question: What are couples' preferences for fresh embryo transfer versus freezing of all embryos followed by frozen embryo transfer and the associated clinical outcomes that may differentiate them?Summary Answer: Couples' preferences are driven by anticipated chances of live birth, miscarriage, neonatal complications, and costs but not by the differences in the treatment process (including delay of embryo transfer linked to frozen embryo transfer and risk of ovarian hyperstimulation syndrome (OHSS) associated with fresh embryo transfer).What Is Known Already: A policy of freezing all embryos followed by transfer of frozen embryos results in livebirth rates which are similar to or higher than those following the transfer of fresh embryos while reducing the risk of OHSS and small for gestational age babies: it can, however, increase the risk of pre-eclampsia and large for gestational age offspring. Hence, the controversy continues over whether to do fresh embryo transfer or freeze all embryos followed by frozen embryo transfer.Study Design, Size, Duration: We used a discrete choice experiment (DCE) technique to survey infertile couples between August 2018 and January 2019.Participants/materials, Setting, Methods: We asked IVF naïve couples attending a tertiary referral centre to independently complete a questionnaire with nine hypothetical choice tasks between fresh and frozen embryo transfer. The alternatives varied across the choice occurrences on several attributes including efficacy (live birth rate), safety (miscarriage rate, neonatal complication rate), and cost of treatment. We assumed that a freeze-all strategy prolonged treatment but reduced the risk of OHSS. An error components mixed logit model was used to estimate the relative value (utility) that couples placed on the alternative treatment approaches and the attributes used to describe them. Willingness to pay and marginal rates of substitution between the non-cost attributes were calculated. A total of 360 individual questionnaires were given to 180 couples who fulfilled the inclusion criteria, of which 212 were completed and returned Our study population included 3 same sex couples (2 females and 1 male) and 101 heterosexual couples. Four questionnaires were filled by one partner only. The response rate was 58.8%.Main Results and the Role Of Chance: Couples preferred both fresh and frozen embryo transfer (odds ratio 27.93 and 28.06, respectively) compared with no IVF treatment, with no strong preference for fresh over frozen. Couples strongly preferred any IVF technique that offered an increase in live birth rates by 5% (P = 0.006) and 15% (P < 0.0001), reduced miscarriage by 18% (P < 0.0001) and diminished neonatal complications by 10% (P < 0.0001). Respondents were willing to pay an additional £2451 (95% CI 604 - 4299) and £761 (95% CI 5056-9265) for a 5 and 15% increase in the chance of live birth, respectively, regardless of whether this involved fresh or frozen embryos. They required compensation of £5230 (95% CI 3320 - 7141) and £13 245 (95% CI 10 110-16 380) to accept a 10 and 25% increase in the risk of neonatal complications, respectively (P < 0.001). Results indicated that couples would be willing to accept a 1.26% (95% CI 1.001 - 1.706) reduction in the live birth rate for a 1% reduction in the risk of neonatal complications per live birth. Older couples appeared to place less emphasis on the risk of neonatal complications than younger couples.Limitations, Reasons For Caution: DCEs can elicit intentions which may not reflect actual behaviour. The external validity of this study is limited by the fact that it was conducted in a single centre with generous public funding for IVF. We cannot rule out the potential for selection or responder bias.Wider Implications Of the Findings: If a strategy of freeze all was to be implemented it would appear to be acceptable to patients, if either success rates can be improved or neonatal complications reduced. Live birth rates, neonatal complication rates, miscarriage rates, and cost are more likely to drive their preferences than a slight delay in the treatment process. The results of this study have important implications for future economic evaluations of IVF, as they suggest that the appropriate balance needs to be struck between success and safety. A holistic approach incorporating patient preferences for expected clinical outcomes and risks should be taken into consideration for individualized care.Study Funding/competing Interest(s): No external funding was sought for this study. A.M. is the chief investigator of the randomized controlled trial 'Freeze all'. S.B. is an Editor in Chief of Human Reproduction Open. The other co-authors have no conflicts of interest to declare. Graham Scotland reports non-financial support from Merck KGaA, Darmstadt, Germany, outside the submitted work.Trial Registration Number: N/A. [ABSTRACT FROM AUTHOR]

Phylogenies are increasingly being used as a basis to provide insight into macroevolutionary history. Here, we use simulation experiments and empirical analyses to evaluate methods that use phylogenies as a basis to make estimates of divergence times and rates of diversification. This is the first study to present a comprehensive assessment of the key variables that underpin analyses in this field—including substitution rates, speciation rates, and extinction, plus character sampling and taxon sampling. We show that in unrealistically simplistic cases (where substitution rates and speciation rates are constant, and where there is no extinction), increased character and taxon sampling lead to more accurate and precise parameter estimates. By contrast, in more complex but realistic cases (where substitution rates, speciation rates, and extinction rates vary), gains in accuracy and precision from increased character and taxon sampling are far more limited. The lack of accuracy and precision even occurs when using methods that are designed to account for more complex cases, such as relaxed clocks, fossil calibrations, and models that allow speciation rates and extinction rates to vary. The problem also persists when analyzing genomic scale data sets. These results suggest two interrelated problems that occur when the processes that generated the data are more complex. First, methodological assumptions are more likely to be violated. Second, limitations in the information content of the data become more important.[Divergence time estimation; diversification rates; macroevolution; phylogeny.] [ABSTRACT FROM AUTHOR]

Understanding and representing uncertainty is crucial in academic research because it enables studies to build on the conclusions of previous studies, leading to robust advances in a particular field. Here, we evaluate the nature of uncertainty and the manner by which it is represented in divergence time estimation, a field that is fundamental to many aspects of macroevolutionary research, and where there is evidence that uncertainty has been seriously underestimated. We address this issue in the context of methods used in divergence time estimation, and with respect to the manner by which time-calibrated phylogenies are interpreted. With respect to methods, we discuss how the assumptions underlying different methods may not adequately reflect uncertainty about molecular evolution, the fossil record, or diversification rates. Therefore, divergence time estimates may not adequately reflect uncertainty and may be directly contradicted by subsequent findings. For the interpretation of time-calibrated phylogenies, we discuss how the use of time-calibrated phylogenies for reconstructing general evolutionary timescales leads to inferences about macroevolution that are highly sensitive to methodological limitations in how uncertainty is accounted for. By contrast, we discuss how the use of time-calibrated phylogenies to test specific hypotheses leads to inferences about macroevolution that are less sensitive to methodological limitations. Given that many biologists wish to use time-calibrated phylogenies to reconstruct general evolutionary timescales, we conclude that the development of methods of divergence time estimation that adequately account for uncertainty is necessary. [Divergence time estimation; macroevolution; uncertainty.] [ABSTRACT FROM AUTHOR]

Purpose: Metabolic syndrome (MetS) is a cluster of metabolic diseases that is linked to atherosclerotic cardiovascular disease. MetS has also been linked to increased nephrolithiasis. However, limited research has been conducted on MetS and its impact on stone-specific health-related quality of life (HRQOL). This study aims to examine the hypothesis that the presence of MetS is associated with decreased HRQOL. Materials and Methods: The Wisconsin Stone Quality of Life Questionnaire, a stone-specific HRQOL questionnaire, was used to survey 3051 patients with kidney stones. Medical history was collected from patients. These data were used to distinguish MetS patients from non-MetS patients. Among patients with current stones, a Wilcoxon rank sum test was used to compare HRQOL scores from MetS patients and non-MetS patients. HRQOL from patients with and without individual MetS components were also compared, and a multivariate analysis was conducted. Results: Statistical comparison between MetS patients (median score 102/140) and non-MetS patients (median score 106/140) demonstrated a lower stone-specific HRQOL in patients with MetS (p = 0.049). Among individual MetS components, patients with diabetes mellitus (DM) or body mass index (BMI) >30 had significantly lower HRQOL than patients without DM or BMI <30 (p = 0.028 and p < 0.001, respectively). The multivariate analysis supported this trend as MetS remained a significant predictor of decreased HRQOL (p = 0.002) after controlling for other variables assessed. Conclusions: This study indicates an association between MetS and a lower stone-specific QOL. This has important implications for stone prevention strategies in patients with MetS. Clinical Trial Registration number: H14-01143 [ABSTRACT FROM AUTHOR]

Introduction: Acquisition costs and prohibitively expensive technical support for endoscope maintenance, repair, and reprocessing have deterred adoption of flexible cystoscopes by many urologists internationally. This study evaluated the performance of a novel single-use digital cystoscope that can directly connect to a laptop or computer monitor for visualization, obviating the need for a tower. Materials and Methods: The performance characteristics of flexible single-use cystoscopes (NeoScope) were prospectively evaluated vs a reusable flexible cystoscope (Olympus) in three clinical cases and two independent benchtop testing episodes in Canada. Cystoscope maneuverability, imaging, deflection, irrigation, and ease of use of instrumentation were investigated. Additional investigations were performed during clinical use in Zimbabwe (7 patients), Egypt (10 patients), and Dominica (5 patients). Results: Bench testing revealed smaller tip diameter (4.06 vs 6.09 mm) and shorter (35.4 vs 38 cm) single-use cystoscopes vs reusable cystoscopes. Deflection of the single-use scope was superior with an empty working channel (230 up/220 down) vs the reusable (195 up/95 down) but showed a more substantial decrease in deflection on placement of instruments including a grasper. Clinical use revealed satisfactory maneuverability, ease of use of instruments, deflection, and visualization. Conclusions: Benchtop testing performance of the single-use digital flexible cystoscopes was inferior compared with reusable digital cystoscopes. However, these single-use endoscopes offer adequate illumination, imaging, and maneuverability. Direct connection to any computer monitor allowed truly portable use, allowing for treatment of patients in a variety of clinical settings without the need for ancillary equipment. [ABSTRACT FROM AUTHOR]

On 4 July 1918, at the Battle of Hamel, the Australian Medical Services used a Field Ambulance Resuscitation Team for the first time, delivering life‐saving blood transfusion and early definitive surgery to badly wounded soldiers very soon after their wounds had been inflicted. During the closing months of the war, many lives and limbs were saved by early resuscitation and effective surgery, an achievement that stands out in marked contrast to the situation in 1914, when inadequate resuscitation, outdated surgical methods and appalling delays in delivering treatment resulted in great numbers of unnecessary deaths. [ABSTRACT FROM AUTHOR]

On 21 March 1918, after nearly 4 years of static warfare on the Western Front, German forces launched a massive offensive from the Hindenburg Line against a depleted British Fifth Army. Elite storm troops smashed through British forward and battle zone positions and advanced more than 17 miles in 2 days. By 5 April, the Germans were outside the town of Villers‐Bretonneux, 40 miles from their starting position and 15 miles from the railway junction of Amiens. This paper examines the response of the Australian Medical Services to the restoration of mobile warfare and explains the measures that were put in place to deal with the evacuation of casualties. [ABSTRACT FROM AUTHOR]

The impact of posttraumatic stress disorder (PTSD) on our combat veterans and their families is extensive. Without support, negative outlook, lack of trust in others, negative perception of self, and lack of trust in one's judgment persist. The support of loved ones is essential to treatment adherence and rehabilitation (Meis, Barry, Kehle, Erbes, & Polusny, 2010). The Veterans Administration (VA) has been using canines to assist combat veterans in reintegrating into civilian life, and most currently as a part of psychological therapy (Rubenstein, 2012). This research examined the impact of receiving and training a service dog on combat veterans with PTSD using Stake's collective case study model. Interviews were conducted with fifteen combat veterans diagnosed with PTSD participating in a 14-week program for receiving and training their own service dog. Anger symptom severity decreases were reported, which had the residual effects of improved relationships and socialization. [ABSTRACT FROM AUTHOR]

Introduction: Current American Urological Association guidelines recommend ureteroscopy (URS) as primary management of distal ureteral stones and shock wave lithotripsy (SWL) as a secondary option. Utilization of SWL in the management of nephrolithiasis in North America has decreased. We hypothesized that SWL continues to be an effective option in the management of distal ureteral calculi and studied data from our center in patients who received SWL for distal ureteral stones. Methods: A retrospective review was performed of 104 patients treated initially with SWL for distal ureteral calculi between 2011 and 2018 at this institution. The success rate of SWL was assessed through radiologic imaging and if subsequent procedures were required to render patients stone free. Results: Operative note and chart review identified 104 patients who presented with distal ureteral stones and were treated with SWL as the initial form of management. Average patient age was 52.2 ± 15.3 years, average BMI was 27.4 ± 5.7, and average total axial stone surface area was 25.96 ± 14.32 mm2. Of these patients, 78.8% (n = 82) were stone free following one SWL and required no subsequent procedures. Of these patients, 87.5% (n = 91) were stone free following a second SWL, and 87.5% (n = 91) were stone free following a secondary URS. After the initial SWL, residual stones were identified in 21.2% of patients (n = 22). Four patients, 3.8%, required a salvage URS following a failed second SWL to achieve stone-free status. Conclusion: One SWL procedure offers a stone-free rate (SFR) of 78.8% and after two SWLs an 87.5% SFR. Only 12.5% of patients undergoing SWL at our center required URS to achieve a stone-free status. SWL is an effective modality in the treatment of distal ureteral stones. [ABSTRACT FROM AUTHOR]

Service dog programs are increasingly being explored as complementary or alternative interventions for military veterans with posttraumatic stress disorder (PTSD). This paper details the results of a control group, pre-and-post pilot investigation evaluating the use of a 14-week service dog training program for veterans in central Florida. Thirty veterans diagnosed with PTSD, 15 in the intervention group and 15 in the waitlist controlled group, completed all pretests and posttests measures, consisting of the 136-item Trauma Symptom Inventory-2 and the 36-item World Health Organization-Disability Assessment Schedule 2.0. Compared to demographically similar veterans in the control group, participants who completed the service dog training program demonstrated significant decreases in posttraumatic symptomatology, intra/interpersonal difficulties associated with psychological trauma, and in disabilities secondary to their PTSD. Study findings, in combination with results from two other recently published controlled investigations, provide evidence supporting the endorsement and use of service dog programs as helpful complementary or alternative treatment options for some veterans. Social work practitioners may want to consider referring their veteran clients with PTSD to qualified service dog programs for adjunctive support when they are having difficulty engaging with or benefiting from office-based traditional therapy approaches. [ABSTRACT FROM AUTHOR]

Flexible ureteroscopy has become an important tool in the urologist's armamentarium. Until recently, reusable ureteroscopes were the only tools available to perform ureteroscopy. However, in recent years, single-use flexible and semirigid ureteroscopes have been developed as an alternative to reusable ureteroscopes. These disposable ureteroscopes were designed to mitigate problems associated with the use of reusable ureteroscopes, including the high costs related to ureteroscope acquisition, maintenance, processing, sterilization, and repairs. In this review, we provide an overview of currently available single-use flexible ureteroscopes, which include LithoVue, Uscope, NeoFlex, and Shaogang, as well as the Neoscope semirigid ureteroscope. The functional capabilities (deflection, irrigation, and optical properties) of each ureteroscope are also discussed. [ABSTRACT FROM AUTHOR]

[Display omitted] The prevalence of immune-mediated disorders, including autoimmune conditions and allergies, is steadily increasing. However, current therapeutic approaches are often non-specific and do not address the underlying pathogenic condition, often resulting in impaired immunity and a state of generalized immunosuppression. The emergence of technologies capable of selectively inhibiting aberrant immune activation in a targeted, antigen (Ag)-specific manner by exploiting the body's intrinsic tolerance pathways, all without inducing adverse side effects, holds significant promise to enhance patient outcomes. In this review, we will describe the body's natural mechanisms of central and peripheral tolerance as well as innovative delivery strategies using cells and biomaterials targeting innate and adaptive immune cells to promote Ag-specific immune tolerance. Additionally, we will discuss the challenges and future opportunities that warrant consideration as we navigate the path toward clinical implementation of tolerogenic strategies to treat immune-mediated diseases. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the effectiveness of ureteroscopy (URS) with laser ablation as an alternative treatment for upper tract urothelial carcinoma (UTUC) lesions larger than 2 cm. Traditionally, patients with large UTUC are treated with radical nephroureterectomy (RNU). However, in patients with pre-existing renal disease, a solitary kidney, or those who decline RNU, management of UTUC may prove challenging METHODS: An institutional database review identified 80 patients with biopsy proven low-grade UTUC who had at least one lesion larger than 2 cm. We collected clinical data including demographics, operative parameters, and pathologic features. Follow-up for all patients was standardized and included cystoscopy and URS every 3 months until clear, every 6 months through the fifth year, and yearly thereafter. We calculated rates of recurrence, progression, and overall survival.Results: In total, 86 unique lesions ≥2cm were identified in the 80 qualifying patients; mean tumor size was 3.04 cm. Median follow-up was 43.6 months. During follow-up of patients treated curatively, 90.5% of tumors had ipsilateral recurrence and 31.7% progressed in grade at a median of 26.3 months. RNU was performed in 16 patients (20%); mean time to surgery was 23.2 months. Overall survival was 75%, and cancer specific survival was 84% at 5-year follow-up.Conclusion: Under strict surveillance, ureteroscopic management of large (≥ 2cm) UTUC lesions is a viable treatment alternative to RNU. While recurrence is common, URS can potentially preserve renal units in patients with large lesions. [ABSTRACT FROM AUTHOR]

Objective: To define the need for emergent intervention between patients with simultaneous bilateral ureteral calculi (SBUC) compared to unilateral ureteral calculi (UUC). Patients with SBUC represent a potential urological emergency due to possible anuria or electrolyte imbalance. While conventional practice mandates immediate intervention in these patients, little data exist to define the rate of these events.Methods: Records of all patients with ureteral stones treated ureteroscopically over an 11-year period were reviewed to identify those with SBUC. Patient presenting characteristics, time from diagnosis to intervention, and postoperative outcomes were noted. To determine the need for emergent intervention, we compared metabolic and infectious parameters between SBUC patients and age- and sex-matched patients with UUC.Results: A total of 3800 patients presented with ureteral calculi including 42 (1.1%) with SBUC. Two-thirds of patients with SBUC had an established diagnosis of nephrolithiasis. Among the 42 patients with SBUC, 11 (26.2%) were considered emergent due to metabolic (5 of 11, 45.5%), infectious (1 of 11, 9.1%), or both metabolic and infectious indications (5 of 11, 45.5%). No patients required acute dialysis before surgical intervention. Compared to patients with UUC, those with SBUC were significantly more likely to require emergent management (P = .03, odds ratio 2.3). Univariate and multivariate analyses showed this to be due to anuria (P = .001) and acidosis (P = .003).Conclusion: SBUC is an uncommon condition and, in this series, only the minority of patients presented emergently. Therefore, patients with SBUC can often be managed electively if counseled on clinical signs warranting emergent medical attention. Appropriately selected patients have excellent outcomes following single stage bilateral ureteroscopy. [ABSTRACT FROM AUTHOR]

Introduction: Advances in flexible ureteroscope design and accessory instrumentation have allowed for more challenging cases to be treated ureteroscopically. Here, we evaluate our experience with ureteroscopy (URS) for the management of large renal calculi (≥2 cm) and provide a concise review of recent reports. Methods: A retrospective review was undertaken of all URS cases between 2004 and 2014 performed by the endourologic team at a single academic tertiary care institution. We identified patients with at least one stone ≥2 cm managed with retrograde URS. Stone size was defined as the largest linear diameter of the index stone. Small diameter flexible ureteroscopes were used primarily with holmium laser. Patient demographics, intraoperative data, and postoperative outcomes were evaluated. Results: We evaluated 167 consecutive patients who underwent URS for large renal stones ≥2 cm. The initial reason for choosing URS included patient preference (29.5%), failure of other therapies (8.2%), anatomic considerations/body habitus (30.3%), and comorbidities (28.8%). Mean patient age was 55.5 years (22–84). The mean stone size was 2.75 cm with mean number of procedures per patient of 1.65 (1–6). The single session stone-free rate was 57.1%, two-stage procedure stone-free rate was 90.2% and three-stage stone-free rate was 94.0%. Access sheaths were used in 47% of patients. An association was identified between stone size and patient outcomes; smaller stones correlated with decreased number of procedures. Postoperative complications were minor. Conclusions: Single or multi-stage retrograde ureteroscopic lithotripsy is a safe and effective mode of surgical management of large renal calculi. Total stone burden is a reliable predictor of the need for a staged procedure and of stone-free rate. [ABSTRACT FROM AUTHOR]

In recent decades there have been a number of studies that have examined the contribution of women in their struggles for social reform and equal rights. Some of these researches have focused more specifically on the roles played by nineteenth century revivalist women in both England and America. They have included the ways in which the growth of industrial society brought changes to religious life and thought that in turn resulted in women moving out of the home and domestic sphere into the mills and factories. In such environments they experienced first-hand the need for reform and were compelled to be more active and vocal in the world beyond their own revivalist gatherings. Other researches have scrutinised the ways in which revivalist women were led into anti-slavery, temperance and purily campaigns. This article aims to take a further step back and examines the inherent nature of revivalist religion and the ways in which it functioned as a vehicle for women in particular as they sought for social justice and equality. [ABSTRACT FROM AUTHOR]

[Display omitted] • Highly imprecise age estimates for angiosperms are generated with minimal assumptions. • Age estimates therefore appear to be fundamentally sensitive to assumptions. • The analysed molecular dataset has minimal effect on age estimates. • Biologically justifiable assumptions are therefore important. Estimates of the age of angiosperms from molecular phylogenies vary considerably. As in all estimates of evolutionary timescales from phylogenies, generating these estimates requires assumptions about the rate that molecular sequences are evolving (using clock models) and the time duration of the branches in a phylogeny (using fossil calibrations and branching processes). Often, it is difficult to demonstrate that these assumptions reflect current knowledge of molecular evolution or the fossil record. In this study we re-estimate the age of angiosperms using a minimal set of assumptions, therefore avoiding many of the assumptions inherent to other methods. The age estimates we generate are similar for each of the four datasets analysed, ranging from 130 to 400 Ma, but are far less precise than in previous studies. We demonstrate that this reduction in precision results from making less stringent assumptions about both rate and time, and that the analysed molecular dataset has very little effect on age estimates. [ABSTRACT FROM AUTHOR]

Objectives: Shock wave lithotripsy (SWL) remains the only effective truly non-invasive treatment for nephrolithiasis. While single-treatment success rates may not equal those of ureteroscopy and percutaneous nephrolithotomy, it has an important role to play in the management of stones. In this paper, we outline the latest evidence-based recommendations for maximizing SWL outcomes, while minimizing complications. Materials and methods: A comprehensive review of the current literature was performed regarding maximizing SWL outcomes. Results: Several different considerations need to be made regarding patient selection with respect to body habitus, body mass index, anatomical location and underlying urologic abnormalities. Stone composition and stone density (Hounsfield Units) are important prognostic variables. Patient positioning is critical to allow for adequate stone localization with either fluoroscopy or ultrasound. Coupling should be optimized with a low viscosity gel applied to the therapy head first and patient movement should be limited. SWL energy should be increased slowly and shockwave rates of 60 or 90 Hz should be used. Medical expulsive therapy with alpha-blockers after SWL treatment has shown benefit, particularly with stones greater than 10 mm. Conclusion: While single-treatment success rates may not equal those of ureteroscopy or percutaneous nephrolithotomy, with proper patient selection, optimization of SWL technique, and use of adjunctive treatment after SWL, success rates can be maximized while further reducing the already low rate of serious complications. SWL remains an excellent treatment option for calculi even in 2017. [ABSTRACT FROM AUTHOR]

Purpose: Intracorporeal lithotripsy is becoming the most commonly used surgical method of stone treatment in Urology. The five major types of intracorporeal lithotripters are ultrasonic, ballistic, and combination lithotripters as well as laser and electrohydraulic lithotripters. The advantages and disadvantages of choosing each of these treatment modalities are reviewed. Methods: Extensive review of literature was performed to identify the types of intracorporeal lithotripters. An investigation was undertaken of the early development of each modality of intracorporeal lithotripsy and/or the mechanism of action. Challenges of each technique were identified and presented. Finally, a determination was made of how these lithotripters compare on the basis of effectiveness of action and cost based on information provided in primary literature as well as previous reviews of these modalities. Results: Contemporary lithotripters have found widespread use in the management of urinary lithiasis. Holmium laser lithotripsy has become one of the most commonly used tools for intracorporeal lithotripsy. Conclusion: There is a wide variety of intracorporeal lithotripters which can be chosen based on the characteristics of each modality and the requirements of the urologist. [ABSTRACT FROM AUTHOR]

Background aims. DUOC-01, a cell product being developed to treat demyelinating conditions, is composed of macrophages that arise from CD14+ monocytes in the mononuclear cell (MNC) population of banked cord blood (CB). This article demonstrates that expression of multiple gene products that promote remyelination is rapidly up-regulated during manufacturing of DUOC-01 from either MNC or purified CB CD14+ monocytes. Methods. Cell cultures were initiated with MNC or with immunoselected CD14+ monocytes isolated from the same CB unit. Cell products present in these cultures after 2 and 3 weeks were compared by three methods. First, quantitative polymerase chain reaction was used to compare expression of 77 transcripts previously shown to be differentially expressed by freshly isolated, uncultured CB CD14+ monocytes and DUOC-01. Second, accumulation of 16 soluble proteins in the culture medium was measured by Bioplex methods. Third, whole transcriptomes of the cell products were compared by microarray analysis. Results. Key transcripts in multiple pathways that promote remyelination were up-regulated in DUOC-01, and substantial secretion of proteins corresponding to many of these transcripts was detected. Cell products manufactured from MNC or from CD14+ monocytes were similar with regard to all metrics. Upregulation of gene products characteristic of DUOC-01 was largely completed within 14 days of culture. Conclusion. We demonstrate that expression of multiple gene products that promote remyelination is upregulated during the first 2 weeks of manufacturing of DUOC-01. Measuring these mechanistically important transcripts and proteins will be useful in monitoring manufacturing, evaluating manufacturing changes, and developing mechanismbased product potency assays. [ABSTRACT FROM AUTHOR]

The National Institute for Health and Clinical Excellence (NICE) invited the manufacturer of denosumab (Amgen Inc., UK) to submit evidence for the clinical and cost effectiveness of denosumab for the prevention of fragility fractures in post-menopausal women, as part of the Institute's single technology appraisal (STA) process. The University of Aberdeen Health Technology Assessment Group were commissioned to act as the Evidence Review Group (ERG); the role of the ERG being to appraise the manufacturer's submission and to produce an independent report. This article provides a description of the company submission, the ERG review and NICE's subsequent decisions. The manufacturer considered that denosumab would be appropriate for patients unable to take, comply with or tolerate oral bisphosphonates. Comparator treatments selected for the submission were, therefore, 'no treatment', raloxifene, strontium ranelate, intravenous zoledronic acid, intravenous ibandronate and teriparatide. The main effectiveness evidence for denosumab was derived from a large randomized controlled trial comparing denosumab with placebo. Given by subcutaneous injection at 6-monthly intervals for 3 years, denosumab reduced the incidence of hip fracture by 40%, and reduced the incidence of clinical vertebral fracture by 69%. An indirect treatment comparison was used to derive adjusted relative risk (RR) estimates for different types of fracture for each comparator versus placebo. The RRs (95% CI) applied for denosumab were 0.316 (0.208, 0.478) for clinical vertebral fracture, 0.605 (0.373, 0.983) for hip fracture and 0.842 (0.638, 1.110) for wrist fracture. Despite a number of concerns surrounding the methodology of the indirect comparison, the ERG was satisfied with the robustness of the effect estimates. The RR estimates were applied in a good-quality Markov model that took account of drug costs, administration and monitoring costs, costs associated with fractures, and long-term nursing home costs. Utility weights were used to adjust time spent in fracture states, allowing QALYs to be estimated. The base-case analysis was conducted for women aged 70 years with a T-score of -2.5 or less and no prior fracture, and women aged 70 years with a T-score of -2.5 or less with a prior fragility fracture. Subgroup analyses based on T-score and independent clinical risk factors were also undertaken. Applying a willingness-to-pay (WTP) threshold of £30 000 per QALY, the manufacturer's results suggested that denosumab would offer a cost-effective alternative to all treatment comparators for the primary and secondary prevention of fractures. The ERG was concerned about an assumption that denosumab would be administered in general practice at the average cost of two standard GP visits a year. As a result, the ERG requested some further sensitivity analysis and undertook some further modelling, applying an assumption that denosumab would be provided primarily in secondary care. This modification altered the cost effectiveness of denosumab versus 'no treatment' (in women with no prior fragility fracture) and zoledronic acid. The NICE Appraisal Committee concluded that, as a treatment option for the prevention of osteoporotic fractures, denosumab should be recommended only in post-menopausal women at increased risk of fracture who cannot comply with the special instructions for administering oral bisphosphonates, or have an intolerance of, or contraindication to, those treatments. For primary prevention, the Appraisal Committee also stipulated specific levels of fracture risk at which denosumab is recommended. [ABSTRACT FROM AUTHOR]

Objective: To assess whether women waiting to undergo in vitro fertilisation (IVF) view adverse outcomes associated with twin pregnancy as more desirable than having no pregnancy at all.Design: Women's preference values for five adverse birth outcomes associated with twin pregnancy were compared with their preference value for treatment failure (TF), i.e. no pregnancy at all.Setting: Aberdeen Fertility Centre, University of Aberdeen, UK.Population: A total of 74 women waiting to undergo IVF.Methods: The standard gamble method was used to elicit women's preference values for giving birth to a child with physical impairments (PI), cognitive impairments (CI), or visual impairments (VI), perinatal death (PD) without a subsequent pregnancy, premature delivery (PremD), and TF (no pregnancy).Main Outcome Measures: Preference values were elicited on a scale where 1 represents giving birth to a healthy child and 0 represents immediate death.Results: The median preference values for having a child with PI, CI, or VI were 0.940, 0.970, and 0.975, respectively. The median values for PremD, PD, and TF were 0.955, 0.725, and 0.815, respectively. Having no child at all was valued significantly lower than having a child with PI, CI, or VI (P < 0.01) but significantly higher than PD (P < 0.01).Conclusions: Some women waiting for IVF treatment view severe child disability outcomes associated with double embryo transfer as being more desirable than having no child at all. Women embarking on IVF may be influenced more strongly by considerations of 'treatment success' rather than future risks to their offspring. [ABSTRACT FROM AUTHOR]

Physiological symptoms of posttraumatic stress disorder (PTSD) manifest as increased arousal and reactivity seen as anger outburst, irritability, reckless behavior with no concern for consequences, hypervigilance, sleep disturbance, and problems with focus (American Psychiatric Association, 2013). In seeking the most beneficial treatment for PTSD, consideration must be given to the anxiety response. Relaxation techniques are shown to help address the physiological manifestations of prolonged stress. The techniques addressed by the authors in this article include mindfulness, deep breathing, yoga, and meditation. By utilizing these techniques traditional therapies can be complemented. In addition, those who are averse to the traditional evidence-based practices or for those who have tried traditional therapies without success; these alternative interventions may assist in lessening physiological manifestations of PTSD. Future research studies assessing the benefits of these treatment modalities are warranted to provide empirical evidence to support the efficacy of these treatments. [ABSTRACT FROM AUTHOR]

Aims To assess the cost-effectiveness of adopting risk-stratified approaches to extended screening intervals in the national diabetic retinopathy screening programme in Scotland. Methods A continuous-time hidden Markov model was fitted to national longitudinal screening data to derive transition probabilities between observed non-referable and referable retinopathy states. These were incorporated in a decision model simulating progression, costs and visual acuity outcomes for a synthetic cohort with a covariate distribution matching that of the Scottish diabetic screening population. The cost-effectiveness of adopting extended (2-year) screening for groups with no observed retinopathy was then assessed over a 30-year time horizon. Results Individuals with a current grade of no retinopathy on two consecutive screening episodes face the lowest risk of progressing to referable disease. For the cohort as a whole, the incremental cost per quality-adjusted life year gained for annual vs. biennial screening ranged from approximately £74 000 (for those with no retinopathy and a prior observed grade of mild or observable background retinopathy) to approximately £232 000 per quality-adjusted life year gained (for those with no retinopathy on two consecutive screening episodes). The corresponding incremental cost-effectiveness ratios in the subgroup with Type 1 diabetes were substantially lower; approximately £22 000 to £85 000 per quality-adjusted life year gained, respectively. Conclusions Biennial screening for individuals with diabetes who have no retinopathy is likely to deliver significant savings for a very small increase in the risk of adverse visual acuity and quality of life outcomes. There is greater uncertainty regarding the long-term cost-effectiveness of adopting biennial screening in younger people with Type 1 diabetes. [ABSTRACT FROM AUTHOR]

Objective: Despite following international guidelines and conducting routine preoperative dietary counseling, every bariatric surgeon will encounter technical challenges in laparoscopic gastric bypass surgery. We present a series of patients in whom the bariatric procedure was stopped after encountering insufficient exposure during diagnostic laparoscopy. These patients were sent back for dietary counseling and underwent surgery after conservative weight loss. The data from this two-step procedure are analyzed and discussed. Methods: This concept was applied and studied in 14 patients from a series of 620 bariatric procedures. Patients who underwent a primary laparoscopic gastric bypass ( n = 593) were used as references. Results: The patients in the study group were significantly heavier than those in the reference group (165 vs. 127 kg, p < 0.001), with 79 % having a BMI >50 kg/m. The patients lost a median of 11 kg after 2 months of conservative treatment, and the mean BMI decreased from 55.7 to 52.6 kg/m. All the patients in the study group underwent laparoscopic surgery for the second procedure with no need for conversion. The complication rate was not elevated in the study group. Overall hospital costs were higher for the study group compared with those for the primary laparoscopic bypass group (27,136 vs. 19,601 USD, p = 0.034). Conclusion: The primary laparoscopic procedure can be stopped in patients with insufficient exposure instead of having them undergo conversion to open surgery. These patients may undergo successful laparoscopic procedures after conservative weight loss with no increased risk and with all of the possible benefits of a laparoscopic approach. As a result of this study, we have established a fixed, preoperative lower limit of 10 % excess weight reduction before accepting superobese patients (BMI >50 kg/m) for surgery at our hospital. [ABSTRACT FROM AUTHOR]

A time-series analysis was used to investigate Arabic undergraduate students’ (n = 50) perceptions of assessed group work in a major government institution of higher education in Qatar. A longitudinal mixed methods approach was employed. Likert scale questionnaires were completed over the duration of a collaborative writing event. Additionally, open-ended questionnaires were administered after the students received their grade for their term paper. This study found that the participants’ perceptions were positive towards assessed group work throughout the duration of the event, changed in a statistically significant way after the submission of the first piece of formally assessed work, and are temporal and liable to change depending on what is experienced. The results of this study suggest that: assessed collaborative writing is a feasible pedagogical tool within higher education; undergraduate learners place value on group work as it enables them to collaboratively generate, share and develop their ideas; and researchers who investigate perceptual or attitudinal changes should consider whether their study requires time-sensitive methodology. [ABSTRACT FROM PUBLISHER]

This study aimed to evaluate the emotion recognition abilities of adults (n=23) with an intellectual disability (ID) compared with a control group of children (n=23) without ID matched for estimated cognitive ability. The study examined the impact of: task paradigm, stimulus type and preferred processing style (global/local) on accuracy. We found that, after controlling for estimated cognitive ability, the control group performed significantly better than the individuals with ID. This provides some support for the emotion specificity hypothesis. Having a more local processing style did not significantly mediate the relation between having ID and emotion recognition, but did significantly predict emotion recognition ability after controlling for group. This suggests that processing style is related to emotion recognition independently of having ID. The availability of contextual information improved emotion recognition for people with ID when compared with line drawing stimuli, and identifying a target emotion from a choice of two was relatively easier for individuals with ID, compared with the other task paradigms. The results of the study are considered in the context of current theories of emotion recognition deficits in individuals with ID. [ABSTRACT FROM AUTHOR]

The author reflects on the crucial condition of election in November 2015 for selection of new secretary general for commonwealth. She mentioned on her two fundamental beliefs including being a black Dominican girl focus on things which are common with other rather than differences and to use our talent in favor of common good. She presents her vision as a candidate for the post of secretary general, to facilitate all the member countries for their benefit from and contribution in commonwealth.

Translesion DNA synthesis (TLS) by specialized DNA polymerases (Pols) is a conserved mechanism for tolerating replication blocking DNA lesions. The actions of TLS Pols are managed in part by ring-shaped sliding clamp proteins. In addition to catalyzing TLS, altered expression of TLS Pols impedes cellular growth. The goal of this study was to define the relationship between the physiological function of Escherichia coli Pol IV in TLS and its ability to impede growth when overproduced. To this end, 13 novel Pol IV mutants were identified that failed to impede growth. Subsequent analysis of these mutants suggest that overproduced levels of Pol IV inhibit E. coli growth by gaining inappropriate access to the replication fork via a Pol III-Pol IV switch that is mechanistically similar to that used under physiological conditions to coordinate Pol IV-catalyzed TLS with Pol III-catalyzed replication. Detailed analysis of one mutant, Pol IV-T120P, and two previously described Pol IV mutants impaired for interaction with either the rim (Pol IVR) or the cleft (Pol IVC) of the β sliding clamp revealed novel insights into the mechanism of the Pol III-Pol IV switch. Specifically, Pol IV-T120P retained complete catalytic activity in vitro but, like Pol IVR and Pol IVC, failed to support Pol IV TLS function in vivo. Notably, the T120P mutation abrogated a biochemical interaction of Pol IV with Pol III that was required for Pol III-Pol IV switching. Taken together, these results support a model in which Pol III-Pol IV switching involves interaction of Pol IV with Pol III, as well as the β clamp rim and cleft. Moreover, they provide strong support for the view that Pol III-Pol IV switching represents a vitally important mechanism for regulating TLS in vivo by managing access of Pol IV to the DNA. [ABSTRACT FROM AUTHOR]

With the rapid rise in social media, alternative news sources, and blogs, ordinary citizens have become information producers as much as information consumers. Highly charged prose, images, and videos spread virally, and stoke the embers of social unrest by alerting fellow citizens to relevant happenings and spurring them into action. We are interested in using Big Data approaches to generate forecasts of civil unrest from open source indicators. The heterogenous nature of data coupled with the rich and diverse origins of civil unrest call for a multi-model approach to such forecasting. We present a modular approach wherein a collection of models use overlapping sources of data to independently forecast protests. Fusion of alerts into one single alert stream becomes a key system informatics problem and we present a statistical framework to accomplish such fusion. Given an alert from one of the numerous models, the decision space for fusion has two possibilities: (i) release the alert or (ii) suppress the alert. Using a Bayesian decision theoretical framework, we present a fusion approach for releasing or suppressing alerts. The resulting system enables real-time decisions and more importantly tuning of precision and recall. Supplementary materials for this article are available online. [ABSTRACT FROM PUBLISHER]

This review systematically examined the literature on the ability of adults with an intellectual disability (ID) to recognise facial expressions of emotion. Studies were included that: recruited only adult participants with ID; that did not specifically recruit participants with co-morbid diagnoses of syndrome(s) related to ID; and that directly compared the performance of adults with ID with a group of people without ID. Nine papers met the eligibility criteria for review and were assessed against pre-defined quality rating criteria and the findings synthesised. The majority of included studies were assessed as being of acceptable overall methodological quality. All of the studies reported a relative impairment in emotion recognition for participants with ID on at least some of the tasks administered, with a large effect size being found for most of the significant results. The review suggests that adults with ID are relatively impaired in recognising facial expressions of emotion, when compared with either adults or children without ID. Methodological variation between studies limits the extent to which any interpretations can be made as to the cause of impaired emotion recognition in adults with ID. [ABSTRACT FROM AUTHOR]