Polyomavirus nephropathy (PVN) is a common viral infection of renal allografts, with biopsy-proven incidence of approximately 5%. A generally accepted morphologic classification of definitive PVN ...that groups histologic changes, reflects clinical presentation, and facilitates comparative outcome analyses is lacking. Here, we report a morphologic classification scheme for definitive PVN from the Banff Working Group on Polyomavirus Nephropathy, comprising nine transplant centers in the United States and Europe. This study represents the largest systematic analysis of definitive PVN undertaken thus far. In a retrospective fashion, clinical data were collected from 192 patients and correlated with morphologic findings from index biopsies at the time of initial PVN diagnosis. Histologic features were centrally scored according to Banff guidelines, including additional semiquantitative histologic assessment of intrarenal polyomavirus replication/load levels. In-depth statistical analyses, including mixed effects repeated measures models and logistic regression, revealed two independent histologic variables to be most significantly associated with clinical presentation: intrarenal polyomavirus load levels and Banff interstitial fibrosis ci scores. These two statistically determined histologic variables formed the basis for the definition of three PVN classes that correlated strongest with three clinical parameters: presentation at time of index biopsy, serum creatinine levels/renal function over 24 months of follow-up, and graft failure. The PVN classes 1-3 as described here can easily be recognized in routine renal biopsy specimens. We recommend using this morphologic PVN classification scheme for diagnostic communication, especially at the time of index diagnosis, and in scientific studies to improve comparative data analysis.
We report
in situ measurements of stress evolution in a silicon thin-film electrode during electrochemical lithiation and delithiation by using the multi-beam optical sensor (MOS) technique. Upon ...lithiation, due to substrate constraint, the silicon electrode initially undergoes elastic deformation, resulting in rapid rise of compressive stress. The electrode begins to deform plastically at a compressive stress of
ca. −1.75
GPa; subsequent lithiation results in continued plastic strain, dissipating mechanical energy. Upon delithiation, the electrode first undergoes elastic straining in the opposite direction, leading to a tensile stress of
ca. 1
GPa; subsequently, it deforms plastically during the rest of delithiation. The plastic flow stress evolves continuously with lithium concentration. Thus, mechanical energy is dissipated in plastic deformation during both lithiation and delithiation, and it can be calculated from the stress measurements; we show that it is comparable to the polarization loss. Upon current interruption, both the film stress and the electrode potential relax with similar time constants, suggesting that stress contributes significantly to the chemical potential of lithiated silicon.
The world food crisis in 2008 highlighted the susceptibility of the global food system to price shocks. Here we use annual staple food production and trade data from 1992-2009 to analyse the changing ...properties of the global food system. Over the 18 year study period, we show that the global food system is relatively homogeneous (85% of countries have low or marginal food self-sufficiency) and increases in complexity, with the number of global wheat and rice trade connections doubling and trade flows increasing by 42 and 90%, respectively. The increased connectivity and flows within these global trade networks suggest that the global food system is vulnerable to systemic disruptions, especially considering the tendency for exporting countries to switch to non-exporting states during times of food scarcity in the global markets. To test this hypothesis, we superimpose continental-scale disruptions on the wheat and rice trade networks. We find greater absolute reductions in global wheat and rice exports along with larger losses in network connectivity as the networks evolve due to disruptions in European wheat and Asian rice production. Importantly, our findings indicate that least developed countries suffer greater import losses in more connected networks through their increased dependence on imports for staple foods (due to these large-scale disturbances): mean (median) wheat losses as percentages of staple food supply are 8.9% (3.8%) for 1992-1996, increasing to 11% (5.7%) for 2005-2009. Over the same intervals, rice losses increase from 8.2% (2.2%) to 14% (5.2%). Our work indicates that policy efforts should focus on balancing the efficiency of international trade (and its associated specialization) with increased resilience of domestic production and global demand diversity.
Charge lost per unit surface area of a silicon electrode due to the formation of solid-electrolyte-interphase (SEI) layer during initial lithiation was quantified, and the species that constitute ...this layer were identified. Coin cells made with Si thin-film electrodes were subjected to a combination of galvanostatic and potentiostatic lithiation and delithiation cycles to accurately measure the capacity lost to SEI layer formation. While the planar geometry of amorphous thin films allows accurate calculation of surface area, creation of additional surface by cracking was prevented by minimizing the thickness of the Si film. The cycled electrodes were analyzed with X-ray photoelectron spectroscopy to characterize the composition of the SEI layer. The charge lost due to SEI formation measured from coin cell experiments was found to be in good agreement with the first-cycle capacity loss during the initial lithiation of a Si(100) crystal with planar geometry. The methodology presented in this work is expected to provide a useful practical tool for battery-material developers in estimating the expected capacity loss due to first cycle SEI layer formation and in choosing an appropriate particle size distribution that balances mechanical integrity and the first cycle capacity loss in large volume expansion electrodes for lithium-ion batteries.
► A method to quantify capacity loss per unit area due to initial SEI formation on Si. ► Identify species that constitute the SEI layer. ► Reported data can be used to predict first-cycle capacity loss on any geometry.
RuO2 is a promising candidate for high-performance electrodes in thin film lithium-ion batteries, due to its large volumetric charge capacity, high rate capability, excellent cyclability and ...compatibility with silicon integrated circuit fabrication techniques. The evolution of mechanical stress associated with the lithiation and delithiation of RuO2 was investigated using in situ stress measurements, and the behavior was found to be fundamentally different from that of previously studied Si and Ge thin film electrodes. Most significantly, the tensile stress during delithiation of RuO2 was found to be very small, especially after the first cycle. The differences can be ascribed to the reversibility of SEI formation on RuO2, which does not occur in the case of Si and Ge. The decomposition of the SEI layer during delithiation allows freer interfacial sliding compared to Si or Ge, which accommodates the stress induced by significant volume changes during cycling. This might explain the relatively better cyclability of RuO2 films compared to Si or Ge films.
Display omitted
•Stress evolution in RuO2 films is fundamentally different from that of Si and Ge.•The tensile stress during delithiation of RuO2 thin films is very small.•The reversible formation of SEI on RuO2 leads to this unique behavior.•RuO2 electrodes form island structures but retain capacity.
 Incidence rate ratio SE 95% CI P value Self-reported exacerbations (yes/no)low * 2.141dagger 0.082 1.99-2.31 <.001 HRUdouble dagger     No. of prescriptions     All cause 1.208 0.015 ...1.18-1.24 <.001 Asthma specific 1.247 0.017 1.22-1.28 <.001 Oral prednisone 1.617 0.067 1.49-1.75 <.001 SABA 1.466 0.029 1.41-1.52 <.001 ICS 1.072 0.016 1.04-1.10 <.001 No. of visits/encounters     All cause     ED 1.356 0.083 1.20-1.53 <.001 Inpatient 1.245 0.115 1.043-1.49 .02 Outpatient 1.129 0.020 1.09-1.17 <.001 Telephone/E-mail encounters 1.121 0.022 1.08-1.16 <.001 Asthma specific     ED 1.586 0.125 1.36-1.85 <.001 Inpatient 1.242 0.123 1.02-1.51 .03 Outpatient 1.277 0.030 1.22-1.34 <.001 Telephone/E-mail encounters 1.441 0.066 1.32-1.58 <.001 Table II Regression results: exacerbations and HRU (incremental effect for a 1-point change in ACQ-5 score per 4 months) Controlling for round and group, age, sex, family income level, race, educational attainment, ethnicity, and smoking status. Sample disposition  No. of surveys completed  Round 1 2681 Round 2 2186 Round 3 1799 All rounds 6666 Baseline demographics n = 2681 Sex (female) 0.65 Mean age (y) 47.9 Age group  12-24 y 0.13 25-34 y 0.11 35-44 y 0.16 45-54 y 0.22 55-64 y 0.26 65-74 y 0.09 75-84 y 0.03 >85 y 0.01 Race  White 0.85 Asian 0.02 African American 0.04 American Indian 0.04 Native Hawaiian 0.01 Multiple race 0.00 NA 0.04 Ethnicity  Hispanic 0.13 Non-Hispanic 0.86 NA 0.01 Income (US dollars/y)  <$10,000 0.02 $10,000-$30,000 0.08 $30,000-$50,000 0.16 $50,000-$70,000 0.15 $70,000-$90,000 0.16 >$90,000 0.31 NA 0.04 No answer 0.08 Education  Less than eighth grade 0.03 High school but did not graduate 0.05 High school graduate or GED 0.14 Some college 0.27 College graduate 0.25 Postgraduate 0.25 NA 0.01 Smoking history  Never smoked 0.66 Current smoker 0.05 Previous smoker 0.28 Allergieslow * 0.74 Employed 0.69 Exacerbationdagger 0.19 Controller adherencelow * 0.77 Table E1 Sample disposition and baseline demographics Data represent proportion of patients, unless otherwise indicated.
Pangolin scales form a durable armor whose hierarchical structure offers an avenue towards high performance bio-inspired materials design. In this study, the fracture resistance of African pangolin ...scales is examined using single edge crack three-point bend fracture testing in order to understand toughening mechanisms arising from the structures of natural mammalian armors. In these mechanical tests, the influence of material orientation and hydration level are examined. The fracture experiments reveal an exceptional fracture resistance due to crack deflection induced by the internal spatial orientation of lamellae. An order of magnitude increase in the measured fracture resistance due to scale hydration, reaching up to ~ 25kJ/m
was measured. Post-mortem analysis of the fracture samples was performed using a combination of optical and electron microscopy, and X-ray computerized tomography. Interestingly, the crack profile morphologies are observed to follow paths outlined by the keratinous lamellae structure of the pangolin scale. Most notably, the inherent structure of pangolin scales offers a pathway for crack deflection and fracture toughening. The results of this study are expected to be useful as design principles for high performance biomimetic applications.
The aim of the study was to assess the rate of insulin independence in patients after total pancreatectomy (TP) and islet autotransplantation in our center. TP followed by islet autotransplantation ...was performed in 10 patients. Severe unrelenting pain associated with chronic pancreatitis was the major indication for surgery. Islets were isolated using the modified Ricordi method and infused through the portal vein. Exogenous insulin therapy was implemented for at least two months posttransplant to support islet engraftment and was subsequently weaned off, if possible. Median follow-up was 26 months (range, 2 to 60 months). Median islet yield was 158,860 islet equivalents (IEQ) (range, 40,203 to 330,472 IEQ) with an average islet yield of 2,478 IEQ/g (range, 685 to 6,002 IEQ/g) of processed pancreas. One patient developed transient partial portal vein thrombosis, which resolved without sequela. Five (50%) patients are currently off insulin with excellent glucose control and HbA1c below 6. Patients who achieved and maintained insulin independence were transplanted with significantly more islets (median, 202,291 IEQ; range, 145,000 to 330,474 IEQ) than patients who required insulin support (64,348 IEQ; range, 40,203 to 260,476 IEQ; P < 0.05). Patient body mass index and time of chronic pancreatitis prior transplant procedure did not correlate with the outcome. The remaining five patients, who require insulin support, had present C-peptide in blood and experience good glucose control without incidence of severe hypoglycemic episodes. Islet autotransplantation efficiently preserved beta cell function in selected patients with chronic pancreatitis and the outcome correlated with transplanted islet mass.
The aim of this study was to assess short-term and long-term results of the pancreatic islet transplantation using the Edmonton protocol at the University of Chicago.
Nine patients underwent ...pancreatic islet cell transplantation using the Edmonton Protocol; they were followed up for 10 years after initial islet transplant with up to 3 separate islet infusions. They were given induction treatment using an IL-2R antibody and their maintenance immunosuppression regimen consisted of sirolimus and tacrolimus.
Nine patients received a total of 18 islet infusions. Five patients dropped out in the early phase of the study. Greater than 50% drop-out and noncompliance rate resulted from both poor islet function and recurrent side effects of immunosuppression. The remaining 4 (44%) patients stayed insulin free with intervals for at least over 5 years (cumulative time) after the first transplant. Each of them received 3 infusions, on average 445 000 islet equivalent per transplant. Immunosuppression regimen required multiple adjustments in all patients due to recurrent side effects. In the long-term follow up, kidney function remained stable, and diabetic retinopathy and polyneuropathy did not progress in any of the patients. Patients' panel reactive antibodies remained zero and anti-glutamic acid decarboxylase 65 antibody did not rise after the transplant. Results of metabolic tests including hemoglobin A1c, arginine stimulation, and mixed meal tolerance test were correlated with clinical islet function.
Pancreatic islet transplantation initiated according to Edmonton protocol offered durable long-term insulin-free glycemic control in only highly selected brittle diabetics providing stable control of diabetic neuropathy and retinopathy and without increased sensitization or impaired renal function. Immunosuppression adjustments and close follow-up were critical for patient retention and ultimate success.
5595 Background: DUO-E (NCT04269200) showed statistically significant, clinically meaningful improvement in progression-free survival (PFS) with addition of durvalumab to CP, followed by durvalumab ± ...the PARP inhibitor olaparib, vs CP alone for patients (pts) with EC (Westin SN et al. J Clin Oncol 2024;42:283–99). PARP inhibitors are an established approach to targeting tumors with homologous recombination deficiency, so we performed post hoc exploratory analyses of PFS by BRCAm status. Methods: Pts with newly diagnosed FIGO Stage III/IV or recurrent EC and naïve to first-line systemic treatment were randomized 1:1:1 to CP (CP + durvalumab placebo pbo; 6 cycles followed by durvalumab pbo + olaparib pbo), CP+D (CP + durvalumab 1120 mg q3w; 6 cycles followed by durvalumab 1500 mg q4w + olaparib pbo) or CP+D+O (CP + durvalumab 6 cycles followed by durvalumab + olaparib 300 mg bid). Tissue BRCAm status was determined retrospectively (FoundationOneCDx assay, Foundation Medicine). Results: Of 718 pts randomized, 19.9% were mismatch repair deficient (dMMR) and 80.1% MMR proficient (pMMR). At primary analysis (April 12, 2023), PFS improvement was observed for CP+D and CP+D+O vs CP irrespective of BRCAm status (Table). BRCAm prevalence was low overall (dMMR: 12.6% BRCAm, 61.5% non-BRCAm, 25.9% unknown; pMMR: 4.0% BRCAm, 65.9% non-BRCAm, 30.1% unknown). PFS outcomes for CP+D+O vs CP in pMMR non-BRCAm pts (HR 0.57, 95% CI 0.42–0.78) were consistent with the overall pMMR subgroup (HR 0.57, 95% CI 0.44–0.73); BRCAm subgroup analyses were descriptive due to small sample size. Conclusions: Clinical benefit with addition of durvalumab to CP, followed by durvalumab + olaparib, vs CP alone was observed in the ITT and pMMR populations irrespective of BRCAm status. Clinical trial information: NCT04269200 . Table: see text
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