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Background and hypothesis: Kidney grafts from donors who died of stroke and related traits have worse outcomes relative to grafts from both living donors and those who died of other causes. We hypothesise that deceased donors, particularly those who died of stroke, have elevated polygenic burden for cerebrovascular traits. We further hypothesise that this donor polygenic burden is associated with inferior graft outcomes in the recipient. Methods: Using a dataset of 6666 deceased and living kidney donors from seven different European ancestry transplant cohorts, we investigated the role of polygenic burden for cerebrovascular traits (hypertension, stroke, and intracranial aneurysm (IA)) on donor age of death and recipient graft outcomes. Results: We found that kidney donors who died of stroke had elevated intracranial aneurysm and hypertension polygenic risk scores, compared to healthy controls and living donors. This burden was associated with age of death among donors who died of stroke. Increased donor polygenic risk for hypertension was associated with reduced long term graft survival (HR: 1.44, 95% CI [1.07, 1.93]) and increased burden for hypertension, and intracranial aneurysm was associated with reduced recipient estimated glomerular filtration rate (eGFR) at 1 year. Conclusions: Collectively, the results presented here demonstrate the impact of inherited factors associated with donors' death on long-term graft function. Graphical Abstract:

Anxiety problems are common in children, yet few affected children access evidence-based treatment. Digitally augmented psychological therapies bring potential to increase availability of effective help for children with mental health problems. This study aimed to establish whether therapist-supported, digitally augmented, parent-led cognitive behavioural therapy (CBT) could increase the efficiency of treatment without compromising clinical effectiveness and acceptability.

IMPORTANCE: Social Determinants of Health (SDOH) have been found to be associated with health outcome disparities in patients with peripheral artery disease (PAD). However, the association of specific components of SDOH and amputation has not been well described. OBJECTIVE: To evaluate whether individual components of SDOH and race are associated with amputation rates in the most populous counties of the US. DESIGN, SETTING, AND PARTICIPANTS: In this population-based cross-sectional study of the 100 most populous US counties, hospital discharge rates for lower extremity amputation in 2017 were assessed using the Healthcare Cost and Utilization Project State Inpatient Database. Those data were matched with publicly available demographic, hospital, and SDOH data. Data were analyzed July 3, 2022, to March 5, 2023. MAIN OUTCOME AND MEASURES: Amputation rates were assessed across all counties. Counties were divided into quartiles based on amputation rates, and baseline characteristics were described. Unadjusted linear regression and multivariable regression analyses were performed to assess associations between county-level amputation and SDOH and demographic factors. RESULTS: Amputation discharge data were available for 76 of the 100 most populous counties in the United States. Within these counties, 15.3% were African American, 8.6% were Asian, 24.0% were Hispanic, and 49.6% were non-Hispanic White; 13.4% of patients were 65 years or older. Amputation rates varied widely, from 5.5 per 100 000 in quartile 1 to 14.5 per 100 000 in quartile 4. Residents of quartile 4 (vs 1) counties were more likely to be African American (27.0% vs 7.9%, P < .001), have diabetes (10.6% vs 7.9%, P < .001), smoke (16.5% vs 12.5%, P < .001), be unemployed (5.8% vs 4.6%, P = .01), be in poverty (15.8% vs 10.0%, P < .001), be in a single-parent household (41.9% vs 28.6%, P < .001), experience food insecurity (16.6% vs 12.9%, P = .04), or be physically inactive (23.1% vs 17.1%, P < .001). In unadjusted linear regression, higher amputation rates were associated with the prevalence of several health problems, including mental distress (β, 5.25 [95% CI, 3.66-6.85]; P < .001), diabetes (β, 1.73 [95% CI, 1.33-2.15], P < .001), and physical distress (β, 1.23 [95% CI, 0.86-1.61]; P < .001) and SDOHs, including unemployment (β, 1.16 [95% CI, 0.59-1.73]; P = .03), physical inactivity (β, 0.74 [95% CI, 0.57-0.90]; P < .001), smoking, (β, 0.69 [95% CI, 0.46-0.92]; P = .002), higher homicide rate (β, 0.61 [95% CI, 0.45-0.77]; P < .001), food insecurity (β, 0.51 [95% CI, 0.30-0.72]; P = .04), and poverty (β, 0.46 [95% CI, 0.32-0.60]; P < .001). Multivariable regression analysis found that county-level rates of physical distress (β, 0.84 [95% CI, 0.16-1.53]; P = .03), Black and White racial segregation (β, 0.12 [95% CI, 0.06-0.17]; P < .001), and population percentage of African American race (β, 0.06 [95% CI, 0.00-0.12]; P = .03) were associated with amputation rate. CONCLUSIONS AND RELEVANCE: Social determinants of health provide a framework by which the associations of environmental factors with amputation rates can be quantified and potentially used to guide interventions at the local level.

Corporate actors have behaved badly in ways that have significantly harmed society. Some of the behavior is illegal - improving enforcement may help. But some of the behavior is not illegal and some is in a grey area. The law’s ability, using its traditional instrumental force, to address the problem is very limited. But penumbral and expressive law can play an important role. Law can encourage firms to take more seriously individual attributes of employees, including executives, in their hiring, firing or other punishment, compensation, and training, and how people with such attributes may interact and influence each other. This encouragement can come from judges’ decisions and regulators’ interactions with firms, and from an articulation of best practices under Caremark. The force of expressive and penumbral law, informed by a more nuanced understanding of people, can be more effective than it thus far has been to limit societal harm.

Misuse of opioids can lead to a potential lethal overdose. Timely administration of naloxone is critical for survival. Here, we designed a polymer–naloxone conjugate that can provide on-demand phototriggered opioid reversal. Naloxone was attached to the polymer poly(lactic-co-glycolic acid) via a photocleavable coumarin linkage and formulated as injectable nanoparticles. In the absence of irradiation, the formulation did not release naloxone. Upon irradiation with blue (400 nm) light, the nanoparticles released free naloxone, reversing the effect of morphine in mice. Such triggered events could be performed days and weeks after the initial administration of the nanoparticles and could be performed repeatedly.

Venous malformations (VMs) consist of hugely enlarged and dysmorphic veins. These lesions cause significant disfigurement, pain, and complications such as bleeding and coagulopathy. Pharmacotherapy for the treatment of VMs has limited efficacy and potentially limiting toxicity. Current treatment for patients with VMs entails life-long pharmacotherapy or surgical procedures. Here we explored whether intravenously administered agents can be used to destroy VMs by photothermal therapy (PTT), using gold nanoshells (AuNSs) that generated heat following irradiation with near-infrared (NIR) light. In a murine model of VMs, intravenous AuNSs accumulated within the VMs. Irradiation of the VMs induced marked regression and even elimination. Nanoparticle-based photothermal therapy can provide effective therapy for VMs, which are otherwise relatively refractory to treatment.

Inadequate drug loading and control of payload leakage limit the duration of the effect of liposomal drug carriers and may cause toxicity. Here, we report a liposome system as a depot for sustained drug delivery whose design is inspired by the low permeability of Archaeal membranes to protons and solutes. Incorporating methyl-branched phospholipids into lipid bilayers decreased payload diffusion across liposomal membranes, thereby enhancing the drug load capacity by 10–16% and reducing the release of small molecules in the first 24 h by 40–48%. The in vivo impact of this approach was demonstrated by injection at the sciatic nerve. Methyl-branched liposomes encapsulating the anesthetic tetrodotoxin (TTX) achieved markedly prolonged local anesthesia lasting up to 70 h, in comparison to the 16 h achieved with liposomes containing conventional lipids. The present work demonstrates the usefulness of methyl-branched liposomes to enhance liposomal depot systems for sustained drug delivery.

Takayasu arteritis is a rare, chronic large vessel vasculitis of unknown etiology which predominantly affects women younger than 40 years of age. Symptoms are highly variable based on the location and extent of the stenosis, arterial occlusion, aneurysm, and thrombosis. Diagnosis is based on clinical presentation, relevant laboratory work-up, and imaging findings of wall thickening and stenosis of medium and large vessels. Management includes glucocorticoid therapy, frequently paired with adjunctive immunosuppressants, and sometimes surgical intervention in severe cases. Here, we present a unique case of Takayasu arteritis with critical distal aortic stenosis with very severe wall thickening involving the bilateral common iliac artery and leading to left iliac artery thrombosis. Based on our literature review, our article represents a very rare presentation of Takayasu arteritis with severe iliac artery thrombosis.

Due to differing perspectives or role boundaries, the working relationships between librarians and technicians have often been fraught with tension and difficulty. If this divide results in a negative team dynamic in the workplace, it can have an impact on the service of the library or information agency and in some cases, its budget. This article disseminates the results of a survey of over 200 library workers conducted by the author in January 2013 on the subject of working relationships. Librarians, library technicians and other support staff across all sectors participated in the survey. The article discusses the tasks that librarians and library technicians often undertake, the differences between the two roles and any areas of role overlap, and areas of tension or difficulty in working relationships. The article also examines some of the reasons why library technicians upgrade their qualifications, and if holding dual (librarian and library technician) credentials has changed their relationships with other library technicians, and introduces ideas to improve relationships, including measures that the industry can take to forge a greater understanding between librarians and library technicians. The potential outcomes can ensure that libraries and information services retain staff.

Little is known of Edmund Husserl's direct encounter with Georg Cantor's ideas on Platonic idealism and the abstraction of number concepts during the late 19th century, when Husserl's philosophical orientation changed considerably and definitely. Closely analyzing and comparing the two men's writings during that important time in their intellectual careers, I describe the crucial shift in Husserl's views on psychologism and metaphysical idealism as it relates to Cantor's philosophy of arithmetic. I thus establish connections between their ideas which have been until now been virtually unsuspected and contribute to a better understanding of the development of Husserl's thought and of the philosophical and metaphysical ideas within which Cantor chose to frame his theories.

Evidence is drawn together to connect sources of inconsistency that Frege discerned in his foundations for arithmetic with the origins of the paradox derived by Russell in Basic LawsI and then with antinomies, paradoxes, contradictions, riddles associated with modal and intensional logics. Examined are: Frege's efforts to grasp logical objects; the philosophical arguments that compelled Russell to adopt a description theory of names and a eliminative theory of descriptions; the resurfacing of issues surrounding reference, descriptions, identity, substitutivity, paradox in the debates concerning modal and intensional logics; the development of the New Theory of Reference. I consider this to be the philosophical ground upon which the debates regarding that theory should take place.

Edmund Husserl was one of the very first to experience the directimpact of challenging problems in set theory and his phenomenology first began to takeshape while he was struggling to solve such problems. Here I study three difficultiesassociated with Frege's use of sets that Husserl explicitly addressed: reference to non-existent, impossible, imaginary objects; the introduction of extensions; and “Russell's” paradox.I do so within the context of Husserl's struggle to overcome the shortcomings of set theory andto develop his own theory of manifolds. I define certain issues involved and discuss howHusserl's theory of manifolds might confront them. In so doing I hope to help bring Husserl'stheories about sets and manifolds out of the realm of abstract theorizing and promptfurther exploration of uncharted philosophical territory rich in philosophical implications.

Retroviruses may cause diseases in their vertebrate hosts. They are distinguished by their common means of replication involving reverse transcription, a process inhibited by nucleoside reverse transcriptase inhibitors (NRTIs) and other compounds used in antiretroviral chemotherapy. Previous work on NRTIs has been limited to their effect on human immunodeficiency virus (HIV) (for review see Ho & Hitchcock, 1989; Weller, 1999) and little information exists regarding the efficacy and therapeutic potential of these drugs against other retroviruses. We have tested all six NRTIs licensed for HIV treatment [didanosine (ddI), zalcitabine (ddC), lamivudine (3TC), stavudine (d4T), zidovudine (AZT) and abacavir (ABC)] against seven retroviruses representative of the traditional subfamilies: Spumavirinae, Lentivirinaeand the Oncovirinae.As expected, each drug showed a range of activities against the panel of retroviruses, some drugs inhibiting other viruses at concentrations well below those required for HIV. Overall, AZT was the most active inhibitor (IC50range, 0.032–1.0 μM), being most active against the Spuma (foamy) viruses. Abacavir was inhibitory for HIV-1, MN strain (HIV-1 MN), amphotrophic murine leukemia virus (MLV-A) and simian foamy virus type 6 (SFV-6). The least effective inhibitor, 3TC (IC50range, 0.32–>100 μM), was most potent against simian retrovirus types 1 and 2 (SRV-1, SRV-2) and HIV-1, but did not inhibit foamy viruses and MLV-A. Additionally, there were differences in the concentration of drug required to inhibit closely related viruses. Taken together, these data suggest that NRTIs have a wide spectrum of antiretroviral activity and the activity of compounds, even against closely related retroviruses, cannot be predicted.

Venous aneurysms of the head and neck region are very uncommon. Aneurysms of the external jugular vein in children are exceedingly rare, and consequently the best approach to diagnosis and management has not been clearly defined. We present the case of a 15-year-old girl with a non-pulsatile, occasionally painful, enlarging fullness in her right supraclavicular fossa and neck. Imaging demonstrated a large and complex right external jugular vein aneurysm with thrombus. Given the symptomatic nature of this aneurysm, recurrent episodes of thrombosis, and the risk of thromboembolism, she underwent surgical excision. Thorough pre-operative planning with additional imaging to better understand the anatomy of this aneurysm was critical to a safe and successful intervention.

Cytoplasmic polyhedrosis virus (CPV) is unique among the double-stranded RNA viruses of the family Reoviridae in having a single capsid layer. Analysis by cryo-electron microscopy allows comparison of the single shelled CPV and orthoreovirus with the high resolution crystal structure of the inner shell of the bluetongue virus (BTV) core. This suggests that the novel arrangement identified in BTV, of 120 protein subunits in a so-called 'T=2' organization, is a characteristic of the Reoviridae and allows us to delineate structural similarities and differences between two subgroups of the family — the turreted and the smooth-core viruses. This in turn suggests a coherent picture of the structural organization of many dsRNA viruses.

Since the launching of the mortgage backed market in the early 1970s, securitization has experienced extraordinary growth and spread to a remarkable variety of receivables. But financial economists in the tradition of Miller and Modigliani have been hard pressed to explain such growth. When viewed within the context of an M & M world of “perfect markets,” securitization appears to be simply another way—and a highly complex and costly one, at that—for a company to carve up its operating cash flows and repackage them for investors.

With emerging markets now in crisis, companies in developing countries are finding it difficult to obtain financing. Securitization, a transaction structure in which the securities sold to investors are backed by a company's receivables, is one of the few vehicles with at least the potential to provide financing at economic rates in the current environment of uncertainty.

Autosomal-dominant Alport syndrome is a recognized, but relatively uncommon, form of Alport syndrome. Recently, mutations in theCOL4A3andCOL4A4genes, which encode collagen type IV α3 and α4 chains, respectively, have been shown to cause the disease. However, the distribution of α(IV) chains has yet to be determined. To clarify the renal distribution of α(IV) chains, immunohistochemistry of α1(IV) to α6(IV) chains was performed, using chain-specific monoclonal antibodies, raised by us, and an antigen retrieval procedure. Paraffin-embedded renal sections, obtained from 8 patients from 3 families with the disease, were examined. The distribution of all 6 α(IV) chains was not significantly different between the 8 patients and the controls. Collagen type IV α1 and α2 chains were ubiquitously expressed, while α3 to α6 chains were detected in the basement membranes of the glomerulus and Bowman's capsule, and/or part of the tubular basement membranes. Our findings contrast with those of X-linked and autosomal-recessive Alport syndrome. The distribution pattern of α(IV) chains may provide a useful means of distinguishing the different forms of Alport syndrome.

Few have entertained the idea that Georg Cantor, the creator of set theory, might have influenced Edmund Husserl, the founder of the phenomenological movement. Yet an exchange of ideas took place between them when Cantor was at the height of his creative powers and Husserl in the throes of an intellectual struggle during which his ideas were particularly malleable and changed considerably and definitively. Here their writings are examined to show how Husserl's and Cantor's ideas overlapped and crisscrossed in the areas of philosophy and mathematics, arithmetization, abstraction, consciousness and pure logic, psychologism, metaphysical idealism, new numbers, and sets and manifolds.

This single center study is the largest series of renal transplant recipients and donors screened for the commonest prothrombotic genotypes. A total of 562 transplant recipients and 457 kidney donors were genotyped for the factor V Leiden and prothrombin G20210A mutations. The prevalence of heterozygous factor V Leiden was 3.4 and 2.6 and prothrombin G20210A was 2.0 and 1.1 in recipients and donors, respectively, similar frequencies to that of the general U.K. population. The 30-day and 1-year graft survival rates in recipients with thrombophilic mutations were 93 and 93, compared with 88 and 82 in patients without these mutations (log-rank P0.34). Thrombophilia in recipients (odds ratio 0.55; confidence interval 0.06–2.29; P0.56) or in donors (odds ratio 1.53; confidence interval 0.27–5.74; P0.46) did not correlate with graft loss at 30 days after transplantation. In contrast to recent reports, this study did not demonstrate an association between thrombophilia and renal allograft loss, and routine screening is not recommended.

We have used a low dose of steroid (20 mg of prednisolone), commencing the day after transplantation, for 151 consecutive renal transplants in 141 patients. Five patients received grafts from living related donors, 146 received cadaver grafts. All patients received azathioprine for routine immunosuppression and the first 47 received a single dose of actinomycin C i.v. for treatment of rejection. No other immunosuppressive drugs were used. This treatment provided satisfactory immunosuppression as 109 of 151 grafts continue to function for periods of 3 months to 10 years and, of 42 grafts lost, only 17 failed from rejection. The cumulative survival of first cadaver grafts at 1 and 2 years in recipients of all ages (7 to 55 years) was 77.9 and 76.0, respectively; in recipients 15 to 34 years old, 90.9 and 86.1, respectively. Twenty-three patients died, no patient died from infection during the admission for transplantation, and infection played a part in the deaths of only four patients. The incidence of other complications was low; seven patients developed gastrointestinal complications, one died, four patients developed diabetes, all survived; only one patient developed avascular necrosis of bone.

Several letters to the editor are presented in response to articles in previous issues including one by María E. Naranjo on Allison-James in the 2007 issue, "Crypto DNA" in the 2007 issue and the review of the book "Beyond Crypto Judaism," in the 2007 issue of La Herencia.

Judge Jed Rakoff has famously written opinions that contain very strong dicta describing his views. In the contexts in which he is writing, law ‘on the books' has not sufficed and probably could not suffice: society has been harmed, and the actors harming it cannot be sufficiently constrained. Judge Rakoff's dicta may help expand law's penumbra to encompass what ‘law on the books' cannot.

The article provides information on the development of a Library Tour program by the Social and Tours Committee in Perth, Western Australia which is intended for delegates of the Libtech 2011 conference.

Presents information on the mentoring program being provided by the Australian Library and Information Association (ALIA) Mentoring New South Wales (NSW) Group. Aims of the ALIA Mentoring NSW Group; Features of the 2005 mentoring program; Success of the mentoring programs.