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2D materials can be isolated as monolayer sheets when interlayer interactions involve weak van der Waals forces. These atomically thin structures enable novel topological physics and open chemical questions of how to tune the structure and properties of the sheets while maintaining them as isolated monolayers. Here, this work investigates 2D electroactive sheets that exfoliate in solution into colloidal nanosheets, but aggregate upon oxidation, giving rise to tunable interlayer charge transfer absorption and photoluminescence. This optical behavior resembles interlayer excitons, now intensely studied due to their long-lived emission, but which remain difficult to tune through synthetic chemistry. Instead, the interlayer excitons of these framework sheets can be modulated through control of solvent, electrolyte, oxidation state, and the composition of the framework building blocks. Compared to other 2D materials, these framework sheets display the largest known interlayer binding strengths, attributable to specific orbital interactions between the sheets, and among the longest interlayer exciton lifetimes. Taken together, this study provides a microscopic basis for manipulating long-range opto-electronic behavior in van der Waals materials through molecular synthetic chemistry., (© 2024 Wiley‐VCH GmbH.)

Understanding and characterizing the intrinsic properties of charge carrier transport across the interfaces in van der Waals heterostructures is critical to their applications in modern electronics, thermoelectrics, and optoelectronics. However, there are very few published cross-plane resistivity measurements of thin samples because these inherently 2-probe measurements must be corrected for contact and lead resistances. Here, we present a method to extract contact resistances and metal lead resistances by fitting the width dependence of the contact end voltages of top and bottom electrodes of different contact widths to a model based on current crowding. These contributions are then subtracted from the total 2-probe cross-plane resistance to obtain the cross-plane resistance of the material itself without needing multiple devices and/or etching steps. This approach was used to measure cross-plane resistivities of a (PbSe) 1 (VSe 2 ) 1 heterostructure containing alternating layers of PbSe and VSe 2 with random in-plane rotational disorder. Several samples measured exhibited a 4 order of magnitude difference between cross-plane and in-plane resistivities over the 6-300 K temperature range. We also reported the observation of charge density wave transition in the cross-plane transport of the (PbSe) 1 (VSe 2 ) 1 heterostructure. The device fabrication process is fully liftoff compatible, and the method developed enables the straightforward measurement of the resistivity anisotropy of most thin film materials with nm thicknesses.

Purpose: Because multiple management options exist for clinical T1 renal masses, patients may experience a state of uncertainty about the course of action to pursue (ie, decisional conflict). To better support patients, we examined patient, clinical, and decision-making factors associated with decisional conflict among patients newly diagnosed with clinical T1 renal masses suspicious for kidney cancer., Materials and Methods: From a prospective clinical trial, participants completed the Decisional Conflict Scale (DCS), scored 0 to 100 with < 25 associated with implementing decisions, at 2 time points during the initial decision-making period. The trial further characterized patient demographics, health status, tumor burden, and patient-centered communication, while a subcohort completed additional questionnaires on decision-making. Associations of patient, clinical, and decision-making factors with DCS scores were evaluated using generalized estimating equations to account for repeated measures per patient., Results: Of 274 enrollees, 250 completed a DCS survey; 74% had masses ≤ 4 cm in size, while 11% had high-complexity tumors. Model-based estimated mean DCS score across both time points was 17.6 (95% CI 16.0-19.3), though 50% reported a DCS score ≥ 25 at least once. On multivariable analysis, DCS scores increased with age (+2.64, 95% CI 1.04-4.23), high- vs low-complexity tumors (+6.50, 95% CI 0.35-12.65), and cystic vs solid masses (+9.78, 95% CI 5.27-14.28). Among decision-making factors, DCS scores decreased with higher self-efficacy (-3.31, 95% CI -5.77 to -0.86]) and information-seeking behavior (-4.44, 95% CI -7.32 to -1.56). DCS scores decreased with higher patient-centered communication scores (-8.89, 95% CI -11.85 to -5.94)., Conclusions: In addition to patient and clinical factors, decision-making factors and patient-centered communication relate with decisional conflict, highlighting potential avenues to better support patient decision-making for clinical T1 renal masses.

Competing Interests: Disclosures Dr Behr has undertaken consulting for Boston Scientific in the last 3 years. The other authors report no conflicts.

Objectives: To develop a method for determining the effect of including drug costs in alternative payment models (APMs)., Study Design: Retrospective claims analysis., Methods: Using the Oncology Care Model as an example, we developed an oncology episode payment model for a commercial payer using historical claims data. We defined 6-month episodes of chemotherapy. Using claims data, we characterized episodes and developed a risk adjustment model. We used bootstrapping to estimate the variation in episode cost with drugs included and without., Results: Episode costs were approximately $100,000. Although absolute cost variation was higher when we included drugs, the percent of total cost represented by variation was lower. Under reasonable assumptions about potential savings from drug and nondrug spending, our results suggest that including drugs in APMs can improve the risk-benefit trade-off faced by provider groups. We introduce a risk-mitigated sharing rate that may enable inclusion of drugs in APMs without substantially increasing downside risk., Conclusions: We have developed a method to assess whether the inclusion of drug spending in APMs is a good decision for provider groups. Including drug costs in episode payments for oncology patients may be preferable for many provider groups.

The interplay between charge transfer and electronic disorder in transition-metal dichalcogenide multilayers gives rise to superconductive coupling driven by proximity enhancement, tunneling and superconducting fluctuations, of a yet unwieldy variety. Artificial spacer layers introduced with atomic precision change the density of states by charge transfer. Here, we tune the superconductive coupling betweenNbSe2monolayers from proximity-enhanced to tunneling-dominated. We correlate normal and superconducting properties inSnSe1+δmNbSe21tailored multilayers with varying SnSe layer thickness (m=1-15). From high-field magnetotransport the critical fields yield Ginzburg-Landau coherence lengths with an increase of140%cross-plane (m=1-9), trending towards two-dimensional superconductivity form>9. We show cross-overs between three regimes: metallic with proximity-enhanced coupling (m=1-4), disordered-metallic with intermediate coupling (m=5-9) and insulating with Josephson tunneling (m>9). Our results demonstrate that stacking metal mono- and dichalcogenides allows to convert a metal/superconductor into an insulator/superconductor system, prospecting the control of two-dimensional superconductivity in embedded layers., (Creative Commons Attribution license.)

Background: Meniscal and chondral damage is common in the patient undergoing revision anterior cruciate ligament (ACL) reconstruction., Purpose: To determine if meniscal and/or articular cartilage pathology at the time of revision ACL surgery significantly influences a patient's outcome at 6-year follow-up., Study Design: Cohort study; Level of evidence, 3., Methods: Patients undergoing revision ACL reconstruction were prospectively enrolled between 2006 and 2011. Data collection included baseline demographics, surgical technique, pathology, treatment, and scores from 4 validated patient-reported outcome instruments: International Knee Documentation Committee (IKDC), Knee injury and Osteoarthritis Outcome Score (KOOS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and Marx Activity Rating Scale. Patients were followed up at 6 years and asked to complete the identical set of outcome instruments. Regression analysis assessed the meniscal and articular cartilage pathology risk factors for clinical outcomes 6 years after revision ACL reconstruction., Results: An overall 1234 patients were enrolled (716 males, 58%; median age, 26 years). Surgeons reported the pathology at the time of revision surgery in the medial meniscus (45%), lateral meniscus (36%), medial femoral condyle (43%), lateral femoral condyle (29%), medial tibial plateau (11%), lateral tibial plateau (17%), patella (30%), and trochlea (21%). Six-year follow-up was obtained on 79% of the sample (980/1234). Meniscal pathology and articular cartilage pathology (medial femoral condyle, lateral femoral condyle, lateral tibial plateau, trochlea, and patella) were significant drivers of poorer patient-reported outcomes at 6 years (IKDC, KOOS, WOMAC, and Marx). The most consistent factors driving outcomes were having a medial meniscal excision (either before or at the time of revision surgery) and patellofemoral articular cartilage pathology. Six-year Marx activity levels were negatively affected by having either a repair/excision of the medial meniscus (odds ratio range, 1.45-1.72; P ≤ .04) or grade 3-4 patellar chondrosis (odds ratio, 1.72; P = .04). Meniscal pathology occurring before the index revision surgery negatively affected scores on all KOOS subscales except for sports/recreation ( P < .05). Articular cartilage pathology significantly impaired all KOOS subscale scores ( P < .05). Lower baseline outcome scores, higher body mass index, being a smoker, and incurring subsequent surgery all significantly increased the odds of reporting poorer clinical outcomes at 6 years., Conclusion: Meniscal and chondral pathology at the time of revision ACL reconstruction has continued significant detrimental effects on patient-reported outcomes at 6 years after revision surgery.

Herpes simplex virus (HSV) and varicella zoster virus (VZV) rely on transport of virus particles in neuronal axons to spread from sites of viral latency in sensory ganglia to peripheral tissues then on to other hosts. This process of anterograde axonal transport involves kinesin motors that move virus particles rapidly along microtubules. α-herpesvirus anterograde transport has been extensively studied by characterizing the porcine pseudorabies virus (PRV) and HSV, with most studies focused on two membrane proteins: gE/gI and US9. It was reported that PRV and HSV US9 proteins bind to kinesin motors, promoting tethering of virus particles on the motors, and furthering anterograde transport within axons. Alternatively, other models have argued that HSV and PRV US9 and gE/gI function in the cytoplasm and not in neuronal axons. Specifically, HSV gE/gI and US9 mutants are defective in the assembly of virus particles in the cytoplasm of neurons and the subsequent sorting of virus particles to cell surfaces and into axons. However, PRV US9 and gE/gI mutants have not been characterized for these cytoplasmic defects. We examined neurons infected with PRV mutants, one lacking both gE/gI and US9 and the other lacking just US9, by electron microscopy. Both PRV mutants exhibited similar defects in virus assembly and cytoplasmic sorting of virus particles to cell surfaces. As well, the mutants exhibited reduced quantities of infectious virus in neurons and in cell culture supernatants. We concluded that PRV US9 primarily functions in neurons to promote cytoplasmic steps in anterograde transport.

Background: The role of prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) imaging in the initial staging of men with prostate cancer (PCa) has yet to be evaluated adequately., Objective: To investigate the concordance of PSMA PET/CT with conventional imaging (CI) with cross-sectional abdominopelvic and/or radionuclide bone imaging in the initial staging of patients with treatment-naïve PCa., Design, Setting, and Participants: We performed a post hoc retrospective cohort study of patients enrolled in a prospective single-arm trial (NCT03368547). We included patients with intermediate-risk (IR) and high-risk (HR) PCa who underwent PSMA PET/CT within 6 mo of CI. Patients with any treatment prior to PSMA PET/CT were excluded. Patient- and tumor-specific data, and imaging findings were obtained., Outcome Measurements and Statistical Analysis: Our primary outcome measurement was the concordance rate of PSMA PET/CT with CI for the identification of N, M1a, M1b, and M1c disease. Descriptive statistics were used., Results and Limitations: A total of 168 patients with treatment-naïve IR and HR PCa met the inclusion criteria. HR disease accounted for 124/168 (73.8%) patients. The median prostate-specific antigen was 11.4 (6.8-24.6)ng/ml. The rates of nonconcordance between PSMA PET/CT and CI were 34/162 (21.0%), 5/70 (7.1%), 8/92 (8.7%), and 1/71 (1.4%) for N, M1a, M1b, and M1c disease, respectively. PSMA PET/CT assigned a higher stage in 37/168 (22.0%) patients and a lower stage in 12/170 (7.1%) patients. In a subset of 50 patients treated with radical prostatectomy and pelvic lymph node dissection, the prevalence of PSMA PET/CT-positive and that of CI-positive nodal disease were 14% and 4%, and the false negative rates were 30% and 32%, respectively. The principal limitations of this study include the heterogeneity in CI modalities and the 6-mo time frame between CI and PSMA PET., Conclusions: PSMA PET/CT imaging may serve as a valuable tool in the initial staging of treatment-naïve IR and HR PCa., Patient Summary: We evaluated how prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) compared with standard imaging (such as computed tomography, bone scan, and prostate magnetic resonance imaging) for initial staging of patients with prostate cancer. Our findings suggest that PSMA PET/CT may detect and rule out more metastatic lesions, which could prove valuable in guiding treatment., (Copyright © 2020 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Controlling charge carrier concentrations remains a major challenge in the application of quasi-two-dimensional materials. A promising approach is the modulation doping of transport channels via charge transfer from neighboring layers in stacked heterostructures. Ferecrystals, which are metastable layered structures created from artificial elemental precursors, are a perfect model system to investigate modulation doping, as they offer unparalleled freedom in the combination of different constituents and variable layering sequences. In this work, differently stacked combinations of rock-salt structured PbSe and VSe 2 were investigated using X-ray photoelectron spectroscopy. The PbSe layers act as electron donors in all heterostructures, with about 0.1 to 0.3 donated electrons per VSe 2 unit cell. While they initially retain their inherent semiconducting behavior, they themselves become metallic when combined with a larger number of VSe 2 layers, as evidenced by a change of the XPS core level lineshape. Additional analysis of the valence band structure was performed for selected stacking orders at different sample temperatures to investigate a predicted charge density wave (CDW) transition. While there appear to be hints of a gap opening, the data so far is inconclusive and the application of spatially resolved techniques such as scanning tunneling microscopy is encouraged for further studies.

Background: Measurement of two grazing management's influence on pasture productivity, soil food web structure, soil organic carbon and soil microbial respiration efficiency was conducted on five southeastern US, across-the-fence ranch pairs to compare adaptive multi-paddock grazing (AMP) management, using short grazing events with planned, adaptive recovery periods, to conventional grazing (CG) management, with continuous grazing at low stock density., Methodology: A point-in-time experimental field analysis was conducted to compare five AMP or CG ranch pairs to better understand the influence of grazing management on (a) standing crop biomass productivity; (b) soil food web community population, structure and functionality; (c) soil organic carbon accrual; and d) soil-C (CO 2 ) respiration kinetics., Results: AMP grazing systems outperformed CG systems by generating: (a) 92.68 g m -2 more standing crop biomass (SCB), promoting 46% higher pasture photosynthetic capacity (Two sample Mann-Whitney; Z = 6.1836; no DF in MW; p  = 6.26 × 10 -10 ; Effect size = 0.35) (b) a strong positive linear relationship of SCB with fungal biomass (R = 0.9915; F(1,3) = 175.35; p  = 0.015); fungal to bacterial (F:B) biomass ratio (R = 0.9616; F(1,3) = 36.75; p  = 0.009) and a soil food web proxy (R = 0.9616; F(1,3) = 36.75; p  = 0.009) and a concurrent very strong inverse relationship with bacteria biomass (R = -0.946; F(1,3) = 25.56; p  = 0.015); (c) significant predator/prey interactions with an inverse relationship with bacterial population biomass ( R  =  - 0.946; F(1,3) = 25.56; p  = 0.015) and a positive relationship with total protozoa enumeration (R = 0.9826; F(1,3) = 83.68; p  = 0.003) when compared to SCB; (d) a 19.52% reduction in soil C (CO 2 ) respiration rates (Two sample t -test; T = -2.3581; DF = 52.3541; p  = 0.0221; Effect size = 0.59); and (e) a 20.6% increase in soil organic carbon (SOC) in the top 10 cm of soil profile (Two sample Mann-Whitney; Z = 2.6507; no DF in MW; p  = 0.008; Effect size = 0.24). Rancher conversion to AMP grazing strategies would appear to regenerate soil food web population, structure, diversity and biological functionality helping to improve: carbon flow into plant biomass, buildup of soil carbon, predator/prey nutrient cycling and soil microbial respiration efficiency while offering improved climate resilience and a strategy to increase the capture and storage of atmospheric CO 2 in soils of the world's rangeland., Competing Interests: David C. Johnson, Richard Teague and Peter Byck declare that they have no competing interests. Steven I. Apfelbaum is a director of Applied Ecological Institute, Inc. and he declares no competing interests. Ry Thompson is an employee of Applied Ecological Services Inc. and he declares no competing interests., (©2022 Johnson et al.)

Background: Lytic or malpositioned tunnels may require bone grafting during revision anterior cruciate ligament reconstruction (rACLR) surgery. Patient characteristics and effects of grafting on outcomes after rACLR are not well described., Purpose: To describe preoperative characteristics, intraoperative findings, and 2-year outcomes for patients with rACLR undergoing bone grafting procedures compared with patients with rACLR without grafting., Study Design: Cohort study; Level of evidence, 3., Methods: A total of 1234 patients who underwent rACLR were prospectively enrolled between 2006 and 2011. Baseline revision and 2-year characteristics, surgical technique, pathology, treatment, and patient-reported outcome instruments (International Knee Documentation Committee [IKDC], Knee injury and Osteoarthritis Outcome Score [KOOS], Western Ontario and McMaster Universities Osteoarthritis Index, and Marx Activity Rating Scale [Marx]) were collected, as well as subsequent surgery information, if applicable. The chi-square and analysis of variance tests were used to compare group characteristics., Results: A total of 159 patients (13%) underwent tunnel grafting-64 (5%) patients underwent 1-stage and 95 (8%) underwent 2-stage grafting. Grafting was isolated to the femur in 31 (2.5%) patients, the tibia in 40 (3%) patients, and combined in 88 patients (7%). Baseline KOOS Quality of Life (QoL) and Marx activity scores were significantly lower in the 2-stage group compared with the no bone grafting group ( P ≤ .001). Patients who required 2-stage grafting had more previous ACLRs ( P < .001) and were less likely to have received a bone-patellar tendon-bone or a soft tissue autograft at primary ACLR procedure ( P ≤ .021) compared with the no bone grafting group. For current rACLR, patients undergoing either 1-stage or 2-stage bone grafting were more likely to receive a bone-patellar tendon-bone allograft ( P ≤ .008) and less likely to receive a soft tissue autograft ( P ≤ .003) compared with the no bone grafting group. At 2-year follow-up of 1052 (85%) patients, we found inferior outcomes in the 2-stage bone grafting group (IKDC score = 68; KOOS QoL score = 44; KOOS Sport/Recreation score = 65; and Marx activity score = 3) compared with the no bone grafting group (IKDC score = 77; KOOS QoL score = 63; KOOS Sport/Recreation score = 75; and Marx activity score = 7) ( P ≤ .01). The 1-stage bone graft group did not significantly differ compared with the no bone grafting group., Conclusion: Tunnel bone grafting was performed in 13% of our rACLR cohort, with 8% undergoing 2-stage surgery. Patients treated with 2-stage grafting had inferior baseline and 2-year patient-reported outcomes and activity levels compared with patients not undergoing bone grafting. Patients treated with 1-stage grafting had similar baseline and 2-year patient-reported outcomes and activity levels compared with patients not undergoing bone grafting.

Background: Patients with anterior cruciate ligament (ACL) revision report lower outcome scores on validated knee questionnaires postoperatively compared to cohorts with primary ACL reconstruction. In a previously active population, it is unclear if patient-reported outcomes (PROs) are associated with a return to activity (RTA) or vary by sports participation level (higher level vs. recreational athletes)., Hypotheses: Individual RTA would be associated with improved outcomes (ie, decreased knee symptoms, pain, function) as measured using validated PROs. Recreational participants would report lower PROs compared with higher level athletes and be less likely to RTA., Study Design: Cohort study; Level of evidence, 2., Methods: There were 862 patients who underwent a revision ACL reconstruction (rACLR) and self-reported physical activity at any level preoperatively. Those who did not RTA reported no activity 2 years after revision. Baseline data included patient characteristics, surgical history and characteristics, and PROs: International Knee Documentation Committee questionnaire, Marx Activity Rating Scale, Knee injury and Osteoarthritis Outcome Score, and the Western Ontario and McMaster Universities Osteoarthritis Index. A binary indicator was used to identify patients with same/better PROs versus worse outcomes compared with baseline, quantifying the magnitude of change in each direction, respectively. Multivariable regression models were used to evaluate risk factors for not returning to activity, the association of 2-year PROs after rACLR surgery by RTA status, and whether each PRO and RTA status differed by participation level., Results: At 2 years postoperatively, approximately 15% did not RTA, with current smokers (adjusted odds ratio [aOR] = 3.3; P = .001), female patients (aOR = 2.9; P < .001), recreational participants (aOR = 2.0; P = .016), and those with a previous medial meniscal excision (aOR = 1.9; P = .013) having higher odds of not returning. In multivariate models, not returning to activity was significantly associated with having worse PROs at 2 years; however, no clinically meaningful differences in PROs at 2 years were seen between participation levels., Conclusion: Recreational-level participants were twice as likely to not RTA compared with those participating at higher levels. Within a previously active cohort, no RTA was a significant predictor of lower PROs after rACLR. However, among patients who did RTA after rACLR, approximately 20% reported lower outcome scores. Most patients with rACLR who were active at baseline improved over time; however, patients who reported worse outcomes at 2 years had a clinically meaningful decline across all PROs.

Human cytomegalovirus (HCMV) entry involves trimer (gH/gL/gO) that interacts with PDGFRα in fibroblasts. Entry into epithelial and endothelial cells requires trimer, which binds unidentified receptors, and pentamer (gH/gL/UL128-131), which binds neuropilin-2. To identify functionally important domains in trimer, we screened an overlapping 20-mer gO peptide library and identified two sets of peptides: 19/20 (a.a. 235-267) and 32/33 (a.a. 404-436) that could block virus entry. Soluble trimer containing wild type gO blocked HCMV entry, whereas soluble trimers with the 19/20 or 32/33 sequences mutated did not block entry. Interestingly, the mutant trimers retained the capacity to bind to cellular receptors including PDGFRα. Peptide 19/20 and 32/33 sequences formed a lobe extending from the surface of gO and an adjacent concave structure, respectively. Neither of these sets of sequences contacted PDGFRα. Instead, our data support a model in which the 19/20 and 32/33 trimer sequences function downstream of receptor binding, e.g. trafficking of HCMV into endosomes or binding to gB for entry fusion. We also screened for peptides that bound antibodies (Abs) in human sera, observing that peptides 20 and 26 bound Abs. These peptides engendered neutralizing Abs (NAbs) after immunization of rabbits and could pull out NAbs from human sera. Peptides 20 and 26 sequences represent the first NAb epitopes identified in trimer. These studies describe two important surfaces on gO defined by: i) peptides 19/20 and 32/33, which apparently act downstream of receptor binding and ii) peptide 26 that interacts with PDGFRα. Both these surfaces are targets of NAbs., Competing Interests: The authors have declared that no competing interests exist.

Many payers and clinicians are committed to advancing value-based care through the establishment of alternative payment models (APMs) that incentivize practices and clinicians to improve quality and reduce cost. A multistakeholder working group has observed that in specialty fields such as oncology, despite many attempts to design and implement APM pilots for commercial and Medicare Advantage populations, practical challenges and small numbers of episodes and patients present headwinds to viability and scalability. Despite this, some payers report emerging good practices and are optimistic about APMs. Careful and realistic consideration of the specific goals of a proposed model is warranted, as is close examination of the feasibility of transferring risk.

This study investigated the impact of seasonal variation and operating conditions on recovery of potable quality water from municipal wastewater effluent using an integrated algal treatment process with a dual forward osmosis (FO)-reverse osmosis (RO) membrane system. Pilot study of the algal process treating primary effluent validated the technical viability and seasonal performance during warm weather (May to October, 25-55 °C) using an extremophilic algal strain Galdieria sulphuraria, and during cold weather (November to April, 4-17 °C) using polyculture strains of algae and bacteria. Algal effluents from both seasons were used as the feed solution for the laboratory FO-RO study. In addition, pilot-scale FO-RO experiments were conducted to compare the system performance during treatment of algal effluent and secondary effluent from the conventional treatment facility. At 90% water recovery, the FO-RO achieved over 90% overall rejection of major ions and organic matter using the bench-scale system and over 99% rejection of all contaminants in pilot-scale studies. Detailed water quality analysis indicated that the product water from the integrated system met both the primary and secondary drinking water standards. This study demonstrated that the FO-RO system can be engineered as a viable alternative to treat algal effluent and secondary effluent for potable water reuse independent of seasonal variations and operating conditions., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Municipal wastewater is a reliable source from which water, renewable energy, and nutrients could be recovered for beneficial use. Our previous efforts have documented that an innovative algal-based wastewater treatment (WWT) system could recover energy and nutrients from wastewater while having a lower energy footprint than conventional WWT processes. As a biological treatment process, the algal WWT can be affected by algal species, operating conditions, and meteorological factors. This study aimed to identify suitable algal cultures to treat municipal wastewater during warm and cold weather. The algal system achieved the secondary effluent discharge standards for biochemical oxygen demand and nutrients within 2-3 days during warm weather (May to October, 25-55 °C) using an extremophilic algal strain Galdieria sulphuraria; and within 1-2 days in winter (November to April, 4-17 °C) using polyculture strains of algae with bacteria. The impact of seasonal variation and operating conditions on the water quality of pilot-scale algal bioreactors was compared with a full-scale conventional WWT system. The treatment performance of the algal system (NH 4 -N: 1.3 ± 1.25 mg/L in winter and not detected in summer and conventional system; PO 4 -P: 0.89 ± 0.6 mg/L in winter, 0.02 ± 0.03 mg/L in summer and, 5.93 ± 1.32 mg/L in conventional system) was comparable or better than that of the conventional WWT in nutrients removal and other contaminants were below the discharge standards. This study indicates that the algal system can be engineered for reliable wastewater treatment independent of seasonal variations., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Herpesvirus capsids are assembled in the nucleus and undergo a two-step process to cross the nuclear envelope. Capsids bud into the inner nuclear membrane (INM) aided by the nuclear egress complex (NEC) proteins UL31/34. At that stage of egress, enveloped virions are found for a short time in the perinuclear space. In the second step of nuclear egress, perinuclear enveloped virions (PEVs) fuse with the outer nuclear membrane (ONM) delivering capsids into the cytoplasm. Once in the cytoplasm, capsids undergo re-envelopment in the Golgi/trans-Golgi apparatus producing mature virions. This second step of nuclear egress is known as de-envelopment and is the focus of this review. Compared with herpesvirus envelopment at the INM, much less is known about de-envelopment. We propose a model in which de-envelopment involves two phases: (i) fusion of the PEV membrane with the ONM and (ii) expansion of the fusion pore leading to release of the viral capsid into the cytoplasm. The first phase of de-envelopment, membrane fusion, involves four herpes simplex virus (HSV) proteins: gB, gH/gL, gK and UL20. gB is the viral fusion protein and appears to act to perturb membranes and promote fusion. gH/gL may also have similar properties and appears to be able to act in de-envelopment without gB. gK and UL20 negatively regulate these fusion proteins. In the second phase of de-envelopment (pore expansion and capsid release), an alpha-herpesvirus protein kinase, US3, acts to phosphorylate NEC proteins, which normally produce membrane curvature during envelopment. Phosphorylation of NEC proteins reverses tight membrane curvature, causing expansion of the membrane fusion pore and promoting release of capsids into the cytoplasm.

Background: Brugada syndrome (BrS) is associated with mutations in the cardiac sodium channel gene, SCN5A. However, genetic studies of patients with BrS with arrhythmic events have been limited. We sought to compare various clinical, ECG, and electrophysiological parameters according to SCN5A genotype in a large cohort of BrS probands with first arrhythmic event., Methods: Survey on Arrhythmic Events in Brugada Syndrome is a survey of 10 Western and 4 Asian countries, gathering 678 patients with BrS with first arrhythmic event. Only probands were included, and SCN5A genotype adjudicated. Patients without appropriate genetic data were excluded. Associations of genotype with clinical features were analyzed., Results: The study group comprised 392 probands: 92 (23.5%) SCN5A+ (44 pathogenic/likely pathogenic [P/LP] and 48 variants of unknown significance) and 300 (76.5%) SCN5A-. SCN5A missense variants and the patients hosting them were similar regardless of adjudication. A higher proportion of patients with P/LP were pediatric (<16 years) compared with SCN5A- (11.4% versus 3%, P =0.023). The proportion of females was higher among patients with P/LP compared with SCN5A - (18.2% versus 6.3%, P =0.013). P/LP probands were more likely to have a family history of sudden cardiac death compared with SCN5A - (41.9% versus 16.8%, P <0.001). A higher proportion of patients with P/LP were White compared with SCN5A- (87.5% versus 47%, P <0.001). Ethnicity (odds ratio, 5.41 [2.8-11.19], P <0.001) and family history of sudden cardiac death (odds ratio, 2.73 [1.28-5.82], P =0.009) were independent variables associated with P/LP genotype following logistic regression., Conclusions: The genetic basis of BrS has a complex relationship with gender, ethnicity, and age. Probands hosting a P/LP variant tended to experience their first arrhythmic event at a younger age and to have events triggered by fever compared with patients with SCN5A- . In addition, they were more likely to be White and to have family history of sudden cardiac death. Among females, a P/LP variant suggests an increased risk of being symptomatic. This association should be further studied on an ethnically specific basis in large prospectively collected international cohorts.

Objectives: Health systems and provider groups currently lack a systematic mechanism to evaluate the financial implications of value-based alternative payments. We sought to develop a method to prospectively quantify the financial implications, including risk and uncertainty of (1) transitioning from a fee-for-service to an episode-based payment model and (2) modifying episode-specific clinical cost drivers. Finally, we highlight practical applications for the model to help facilitate stakeholder engagement in the transition to value-based payment models., Study Design: We created a financial simulation from empirical data to demonstrate the feasibility and potential use cases within the context of a hypothetical episode-based payment model for prostate cancer surgery (prostatectomy)., Methods: We used Monte Carlo simulation methods to predict financial outcomes under various clinical and payment model scenarios for our pilot prostatectomy episode use case. We input patient-level empirical cost, reimbursement, and clinical data for a cohort of 157 patients at our institution into our model to quantify expected financial outcomes (payments, financial margins) and financial risk for stakeholders (payer, hospital, providers) under an episode-based payment model., Results: Compared with the status quo, there is a range of expected financial outcomes for various stakeholders depending on the financial parameters (episode price, shared savings, downside risk, stop-loss) in an episode-based payment model. Modifying clinical cost drivers has a profound impact on these outcomes. Uncertainty is high due to the small number of episodes., Conclusions: The simulation demonstrates that both financial parameters and clinical cost drivers significantly affect the expected financial outcomes for stakeholders in value-based payment models.

Background: Although graft choice may be limited in the revision setting based on previously used grafts, most surgeons believe that graft choice for anterior cruciate ligament (ACL) reconstruction is an important factor related to outcome., Hypothesis: In the ACL revision setting, there would be no difference between autograft and allograft in rerupture rate and patient-reported outcomes (PROs) at 6-year follow-up., Study Design: Cohort study; Level of evidence, 2., Methods: Patients who had revision surgery were identified and prospectively enrolled in this cohort study by 83 surgeons over 52 sites. Data collected included baseline characteristics, surgical technique and pathology, and a series of validated PRO measures. Patients were followed up at 6 years and asked to complete the identical set of PRO instruments. Incidence of additional surgery and reoperation because of graft failure were also recorded. Multivariable regression models were used to determine the predictors (risk factors) of PROs, graft rerupture, and reoperation at 6 years after revision surgery., Results: A total of 1234 patients including 716 (58%) men were enrolled. A total of 325 (26%) underwent revision using a bone-patellar tendon-bone (BTB) autograft; 251 (20%), soft tissue autograft; 289 (23%), BTB allograft; 302 (25%), soft tissue allograft; and 67 (5%), other graft. Questionnaires and telephone follow-up for subsequent surgery information were obtained for 809 (66%) patients, while telephone follow-up was only obtained for an additional 128 patients for the total follow-up on 949 (77%) patients. Graft choice was a significant predictor of 6-year Marx Activity Rating Scale scores ( P = .024). Specifically, patients who received a BTB autograft for revision reconstruction had higher activity levels than did patients who received a BTB allograft (odds ratio [OR], 1.92; 95% CI, 1.25-2.94). Graft rerupture was reported in 5.8% (55/949) of patients by their 6-year follow-up: 3.5% (16/455) of patients with autografts and 8.4% (37/441) of patients with allografts. Use of a BTB autograft for revision resulted in patients being 4.2 times less likely to sustain a subsequent graft rupture than if a BTB allograft were utilized ( P = .011; 95% CI, 1.56-11.27). No significant differences were found in graft rerupture rates between BTB autograft and soft tissue autografts ( P = .87) or between BTB autografts and soft tissue allografts ( P = .36). Use of an autograft was found to be a significant predictor of having fewer reoperations within 6 years compared with using an allograft ( P = .010; OR, 0.56; 95% CI, 0.36-0.87)., Conclusion: BTB and soft tissue autografts had a decreased risk in graft rerupture compared with BTB allografts. BTB autografts were associated with higher activity level than were BTB allografts at 6 years after revision reconstruction. Surgeons and patients should consider this information when choosing a graft for revision ACL reconstruction.

There have been a number of surprising reports of unexpected products when preparing heterostructures of Bi 2 Se 3 with other 2D layers. These reports prompted us to explore the formation of metastable heterostructures containing Bi 2 Se 3 using X-ray diffraction techniques to follow the reaction pathway. We discovered that the products formed depend on the electronic properties of the second constituent. Bi|Se layers deposited in a 2:3 ratio with enough atoms to make a single five-plane layer evolved to form thermodynamically stable Bi 2 Se 3 as expected from the phase diagram. When the same Bi|Se layers were sequentially deposited with M|Se layers that form semiconductor layers (PbSe and 2H-MoSe 2 ), Bi 2 Se 3 -containing heterostructures formed. When the same Bi|Se layers were deposited with M|Se layers that form metallic layers (TiSe 2, VSe 2 , and 1T-MoSe 2 ), BiSe-containing heterostructures formed. The amount of excess Se in the precursor controls whether [(Bi 2 Se 3 ) 1+δ ] 1 [(MoSe 2 )] 1 or [(BiSe) 1+γ ] 1 [(MoSe 2 )] 1 forms. XPS data indicates that a mixture of both metallic 1T and semiconducting 2H-MoSe 2 is present in [(BiSe) 1+γ ] 1 [(MoSe 2 )] 1 , while only semiconducting 2H-MoSe 2 is present when layered with Bi 2 Se 3 . The electronic structure of adjacent layers impacts the formation of different structures from layers with similar local compositions. This provides an important additional parameter to consider when designing the synthesis of heterostructures, similar to substituent effects in molecular chemistry.

α-herpesviruses have been very successful, principally because they establish lifelong latency in sensory ganglia. An essential piece of the lifecycle of α-herpesviruses involves the capacity to travel from sensory neurons to epithelial tissues following virus reactivation from latency, a process known as anterograde transport. Virus particles formed in neuron cell bodies hitchhike on kinesin motors that run along microtubules, the length of axons. Herpes simplex virus (HSV) and pseudorabies virus (PRV) have been intensely studied to elucidate anterograde axonal transport. Both viruses use similar strategies for anterograde transport, although there are significant differences in the form of virus particles transported in axons, the identity of the kinesins that transport viruses, and how certain viral membrane proteins, gE/gI and US9, participate in this process. This review compares the older models for HSV and PRV anterograde transport with recent results, which are casting a new light on several aspects of this process., (Copyright © 2021. Published by Elsevier Inc.)

Background. Multiple studies have shown that digitally mediated decision aids help prepare patients for medical decision making with their providers. However, few studies have investigated whether decision-support preferences differ between non-English-speaking and English-speaking Latino men with limited literacy. Objective. To identify and compare health information seeking patterns, preferences for information presentation, and interest in digital decision aids in a sample of Southern Californian underserved Latino men with newly diagnosed prostate cancer at a county hospital. Methods. We conducted semistructured, in-depth telephone interviews with 12 Spanish-speaking and 8 English-speaking Latino men using a purposive sampling technique. Following transcription of taped interviews, Spanish interviews were translated. Using a coding protocol developed by the team, two bilingual members jointly analyzed the transcripts for emerging themes. Coder agreement exceeded 80%. Differences were resolved through discussion. Results. Thematic differences between groups with different preferred languages emerged. Most respondents engaged in online health information seeking using cellphones, perceived a paternalistic patient-provider relationship, and expressed willingness to use hypothetical digital decision aids if recommended by their provider. English speakers reported higher digital technology proficiency for health-related searches. They also more frequently indicated family involvement in digital search related to their condition and preferred self-guided, web-based decision aids. In comparison, Spanish speakers reported lower digital technology proficiency and preferred family-involved, coach-guided, paper and visual decision aids. English speakers reported substantially higher levels of formal education. Conclusion. Preferences regarding the use of digital technology to inform prostate cancer treatment decision making among underserved Latino men varied depending on preferred primary language. Effective preparation of underserved Latino men for shared decision making requires consideration of alternative approaches depending on level of education attainment and preferred primary language., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2021.)

Prostate cancer is a complex disease that affects millions of men globally, predominantly in high human development index regions. Patients with localized disease at a low to intermediate risk of recurrence generally have a favourable outcome of 99% overall survival for 10 years if the disease is detected and treated at an early stage. Key genetic alterations include fusions of TMPRSS2 with ETS family genes, amplification of the MYC oncogene, deletion and/or mutation of PTEN and TP53 and, in advanced disease, amplification and/or mutation of the androgen receptor (AR). Prostate cancer is usually diagnosed by prostate biopsy prompted by a blood test to measure prostate-specific antigen levels and/or digital rectal examination. Treatment for localized disease includes active surveillance, radical prostatectomy or ablative radiotherapy as curative approaches. Men whose disease relapses after prostatectomy are treated with salvage radiotherapy and/or androgen deprivation therapy (ADT) for local relapse, or with ADT combined with chemotherapy or novel androgen signalling-targeted agents for systemic relapse. Advanced prostate cancer often progresses despite androgen ablation and is then considered castration-resistant and incurable. Current treatment options include AR-targeted agents, chemotherapy, radionuclides and the poly(ADP-ribose) inhibitor olaparib. Current research aims to improve prostate cancer detection, management and outcomes, including understanding the fundamental biology at all stages of the disease.

Purpose: Oncologic efficacy of focal therapies in prostate cancer depends heavily on accurate tumor size estimation. We aim to evaluate the agreement between radiologic tumor size and pathological tumor size, and identify predictors of pathological tumor size., Materials and Methods: This single arm study cohort included all consecutive patients with biopsy proven prostate cancer and a corresponding PI-RADS®v2 3 or greater index tumor on multiparametric magnetic resonance imaging who subsequently underwent radical prostatectomy. Radiologic tumor size was defined as maximum tumor diameter on multiparametric magnetic resonance imaging and compared to whole mount histopathology tumor correlates. The difference between radiologic tumor size and pathological tumor size was assessed, and clinical, pathological and radiographic predictors of pathological tumor size were examined., Results: A total of 461 consecutive lesions in 441 men were included for statistical analysis. Mean radiologic tumor size and pathological tumor size was 1.57 and 2.37 cm, respectively (p <0.001). Radiologic tumor size consistently underestimated pathological tumor size regardless of the preoperative covariates, and the degree of underestimation increased with smaller radiologic tumor size and lower PI-RADSv2 scores. Pathological tumor size was significantly larger for biopsy Gleason Grade Group (GG) 5 compared to GG1 (mean change 0.37 cm, p=0.014), PI-RADSv2 5 lesions compared to PI-RADSv2 4 (mean change 0.26, p=0.006) and higher prostate specific antigen density. The correlations between radiologic tumor size vs pathological tumor size according to biopsy GG and radiologic covariates were generally low with correlation coefficients ranging between 0.1 and 0.65., Conclusions: Multiparametric magnetic resonance imaging frequently underestimates pathological tumor size and the degree of underestimation increases with smaller radiologic tumor size and lower PI-RADSv2 scores. Therefore, a larger ablation margin may be required for smaller tumors and lesions with lower PI-RADSv2 scores. These variables must be considered when estimating treatment margins in focal therapy.

Infection is a rare occurrence after revision anterior cruciate ligament reconstruction (rACLR). Because of the low rates of infection, it has been difficult to identify risk factors for infection in this patient population. The purpose of this study was to report the rate of infection following rACLR and assess whether infection is associated with patient- and surgeon-dependent risk factors. We reviewed two large prospective cohorts to identify patients with postoperative infections following rACLR. Age, sex, body mass index (BMI), smoking status, history of diabetes, and graft choice were recorded for each patient. The association of these factors with postoperative infection following rACLR was assessed. There were 1423 rACLR cases in the combined cohort, with 9 (0.6%) reporting postoperative infections. Allografts had a higher risk of infection than autografts (odds ratio, 6.8; 95% CI, 0.9-54.5; p = .045). Diabetes (odds ratio, 28.6; 95% CI, 5.5-149.9; p = .004) was a risk factor for infection. Patient age, sex, BMI, and smoking status were not associated with risk of infection after rACLR., (© 2020 Orthopaedic Research Society. Published by Wiley Periodicals LLC.)

Purpose: To assess the impact of N-methylnaltrexone, a peripherally acting mu-opioid receptor antagonist, on the post-operative recovery of patients undergoing robotic-assisted radical cystectomy for bladder cancer., Methods: We retrospectively reviewed patients undergoing robotic-assisted radical cystectomy by a single surgeon (KC) prior to (control group) and after (treatment group) the routine use of N-methylnaltrexone. Kaplan-Meier curves and the log-rank test were used to quantify time to flatus, bowel movement, and discharge. Daily mean opioid use, daily pain assessment rating, and episodes of severe pain (7-10/10) were compared. Gastrointestinal-related complications, including ileus, emesis, and/or need for post-op nasogastric tube placement, and 30-day readmissions were also compared between groups. Charge capture data were compared between groups to analyze cost impact., Results: 29 patients each in the control and treatment group met inclusion criteria. Patients receiving N-methylnaltrexone had reduced length of stay compared with no N-methylnaltrexone (median 4 vs. 7 days, p < 0.01). Time to flatus and bowel movement, however, were similar. In a multivariable analysis controlling for possible confounders, however, the improvement in length of stay associated with N-methylnaltrexone use did not reach statistical significance (p = 0.11). Episodes of severe pain and composite gastrointestinal-related complications were reduced in the N-methylnaltrexone group (44.8% vs. 10.3%, p < 0.01). The reduction in length of stay was associated with approximately $10,500 in cost savings per patient., Conclusions: In this study, N-methylnaltrexone was associated with reduced length of stay, fewer episodes of severe pain, and reduced costs. These results provide the impetus for further study.

We explore the effect of charge density wave (CDW) on the in-plane thermoelectric transport properties of (PbSe) 1+δ (VSe 2 ) 1 and (PbSe) 1+δ (VSe 2 ) 2 heterostructures. In (PbSe) 1+δ (VSe 2 ) 1 we observe an abrupt 86% increase in the Seebeck coefficient, 245% increase in the power factor, and a slight decrease in resistivity over the CDW transition. This behavior is not observed in (PbSe) 1+δ (VSe 2 ) 2 and is rather unusual compared to the general trend observed in other materials. The abrupt transition causes a deviation from the Mott relationship through correlated electron states. Raman spectra of the (PbSe) 1+δ (VSe 2 ) 1 material show the emergence of additional peaks below the CDW transition temperature associated with VSe 2 material. Temperature-dependent in-plane X-ray diffraction (XRD) spectra show a change in the in-plane thermal expansion of VSe 2 in (PbSe) 1+δ (VSe 2 ) 1 due to lattice distortion. The increase in the power factor and decrease in the resistivity due to CDW suggest a potential mechanism for enhancing the thermoelectric performance at the low temperature region.

The herpes simplex virus (HSV) heterodimer gE/gI and another membrane protein, US9, which has neuron-specific effects, promote the anterograde transport of virus particles in neuronal axons. Deletion of both HSV gE and US9 blocks the assembly of enveloped particles in the neuronal cytoplasm, which explains why HSV virions do not enter axons. Cytoplasmic envelopment depends upon interactions between viral membrane proteins and tegument proteins that encrust capsids. We report that tegument protein UL16 is unstable, i.e., rapidly degraded, in neurons infected with a gE-/US9- double mutant. Immunoprecipitation experiments with lysates of HSV-infected neurons showed that UL16 and three other tegument proteins, namely, VP22, UL11, and UL21, bound either to gE or gI. All four of these tegument proteins were also pulled down with US9. In neurons transfected with tegument proteins and gE/gI or US9, there was good evidence that VP22 and UL16 bound directly to US9 and gE/gI. However, there were lower quantities of these tegument proteins that coprecipitated with gE/gI and US9 from transfected cells than those of infected cells. This apparently relates to a matrix of several different tegument proteins formed in infected cells that bind to gE/gI and US9. In cells transfected with individual tegument proteins, this matrix is less prevalent. Similarly, coprecipitation of gE/gI and US9 was observed in HSV-infected cells but not in transfected cells, which argued against direct US9-gE/gI interactions. These studies suggest that gE/gI and US9 binding to these tegument proteins has neuron-specific effects on virus HSV assembly, a process required for axonal transport of enveloped particles. IMPORTANCE Herpes simplex viruses 1 and 2 and varicella-zoster virus cause significant morbidity and mortality. One basic property of these viruses is the capacity to establish latency in the sensory neurons and to reactivate from latency and then cause disease in peripheral tissues, such as skin and mucosal epithelia. The transport of nascent HSV particles from neuron cell bodies into axons and along axons to axon tips in the periphery is an important component of this reactivation and reinfection. Two HSV membrane proteins, gE/gI and US9, play an essential role in these processes. Our studies help elucidate how HSV gE/gI and US9 promote the assembly of virus particles and sorting of these virions into neuronal axons., (Copyright © 2020 American Society for Microbiology.)

Background: Meniscal preservation has been demonstrated to contribute to long-term knee health. This has been a successful intervention in patients with isolated tears and tears associated with anterior cruciate ligament (ACL) reconstruction. However, the results of meniscal repair in the setting of revision ACL reconstruction have not been documented., Purpose: To examine the prevalence and 2-year operative success rate of meniscal repairs in the revision ACL setting., Study Design: Case-control study; Level of evidence, 3., Methods: All cases of revision ACL reconstruction with concomitant meniscal repair from a multicenter group between 2006 and 2011 were selected. Two-year follow-up was obtained by phone and email to determine whether any subsequent surgery had occurred to either knee since the initial revision ACL reconstruction. If so, operative reports were obtained, whenever possible, to verify the pathologic condition and subsequent treatment., Results: In total, 218 patients (18%) from 1205 revision ACL reconstructions underwent concurrent meniscal repairs. There were 235 repairs performed: 153 medial, 48 lateral, and 17 medial and lateral. The majority of these repairs (n = 178; 76%) were performed with all-inside techniques. Two-year surgical follow-up was obtained on 90% (197/218) of the cohort. Overall, the meniscal repair failure rate was 8.6% (17/197) at 2 years. Of the 17 failures, 15 were medial (13 all-inside, 2 inside-out) and 2 were lateral (both all-inside). Four medial failures were treated in conjunction with a subsequent repeat revision ACL reconstruction., Conclusion: Meniscal repair in the revision ACL reconstruction setting does not have a high failure rate at 2-year follow-up. Failure rates for medial and lateral repairs were both <10% and consistent with success rates of primary ACL reconstruction meniscal repair. Medial tears underwent reoperation for failure at a significantly higher rate than lateral tears.

The reaction of ultrathin layers of Mo and Ti with Se was investigated, and significantly different reaction pathways were found. However, in both systems postdeposition annealing results in smooth dichalcogenide films with specific thicknesses determined by the precursor. X-ray diffraction (XRD) patterns of as-deposited Mo|Se films around a 1:2 ratio of Mo to Se contain weak, broad reflections from small and isolated MoSe 2 crystallites that nucleated during deposition and a sharper intensity maximum resulting from the composition modulation created from the alternating deposition of Mo and Se layers. In contrast, as-deposited Ti|Se films around a 1:2 ratio of Ti to Se contain narrow and intense 00 l reflections from TiSe 2 crystallites and do not contain a Bragg reflection from the sequence of deposited Ti|Se layers. The as-deposited TiSe 2 crystallites have a larger c- axis lattice parameter than was previously reported for TiSe 2 , however, which suggests a poor vertical interlayer registry and/or high defect densities including interstitial atoms. In-plane XRD patterns show the nucleation of both TiSe 2 and Ti 2 Se during deposition, with the Ti 2 Se at the substrate. For both systems, annealing the precursors decreases the peak width and increases the intensity of reflections from crystalline TiSe 2 and MoSe 2 . Optimized films consist of a single phase after the annealing and show clear Laue oscillations in the specular XRD patterns, which can only occur if a majority of the diffracting crystallites in the film consist of the same number of unit cells. The highest quality films was obtained when an excess of ∼10% Se was deposited in the precursor, which presumably acts as a flux to facilitate diffusion of metal atoms to crystallite growth fronts and compensates for Se loss to the open system during annealing.

This work presents the preparation of a series of [(PbSe) 1+δ ] 4 [TiSe 2 ] 4 isomers via a low temperature synthesis approach that exploits precursor nanoarchitecture to direct formation of specific isomers. The targeted isomers formed even when the precursors did not have the correct amount of each element to make a unit cell from each repeating sequence of elemental layers deposited. This suggests that the exact composition of the precursors is less important than the nanoarchitecture in directing the formation of the compounds. The as-deposited diffraction data show that the isomers begin to form during the deposition, and Ti 2 Se, in addition to PbSe and TiSe 2 , are present in the specular diffraction patterns. HAADF-STEM images reveal impurity layers above and below an integer number of targeted isomer unit cells. The structural data suggest that Ti 2 Se forms as Se is deposited on the initial Ti layers and remains throughout isomer self-assembly. During growth, the isomers deplete the local supply of Ti and Pb, creating diffusion gradients that drive additional cations toward the growth front, which leaves surface impurity layers of TiSe 2 and TiO 2 after the supply of Pb is exhausted. The deposited stacking sequences direct formation of the targeted isomers, but fewer repeating units form than intended due to the lack of material per layer in the precursor and formation of impurity layers. All isomers have negative Hall and Seebeck coefficients, indicating that electrons are the majority carrier. The carrier concentration and conductivity of the isomers increase with the number of interfaces in the unit cell, resulting from charge donation between adjacent layers. The opposite variation of the carrier concentration and mobility with temperature result in minima in the resistivity between 50 and 100 K. The very weak temperature dependence of the carrier concentration likely results from changes in the amount of charge transfer between the layers with temperature.

Introduction: Renal mass biopsy (RMB) may not be indicated when the results are unlikely to impact management, such as in young and/or healthy patients and in elderly and/or frail patients. We analyzed the utility of RMB in three patient cohorts stratified by age-adjusted Charlson comorbidity index score (ACCI)., Materials and Methods: We identified patients with cT1a renal tumors in the National Cancer Database from 2004-2014. We combined age and Charlson-Deyo scores to identify young and/or healthy patients ('healthy-ACCI'), elderly and/or frail patients ('frail-ACCI'), and a reference cohort. We performed multivariable logistic regression to identify predictors of RMB and treatment. We evaluated the impact of RMB on management by analyzing the proportion of high-grade disease on final pathology as a surrogate for risk stratification., Results: We identified 36,720 healthy-ACCI, 2,516 frail-ACCI, and 18,989 reference-ACCI patients. Healthy-ACCI patients were less likely to undergo RMB (7.5% versus 10.8%; p < 0.001) while frail-ACCI patients underwent RMB at similar rates (11.8% versus 10.8%; p = 0.14) compared with reference-ACCI patients. On multivariable logistic regression, in both healthy-ACCI and frail-ACCI patients, RMB was associated with decreased odds of surgical treatment, and increased odds of ablation and surveillance (all p < 0.01). In the frail-ACCI patients, higher grade disease at surgery was identified in the RMB cohort (32.9% versus 23.5%, p = 0.05)., Conclusions: RMB is performed less frequently in healthy-ACCI patients compared with the reference cohort. RMB is associated with decreased odds of surgical treatment and increased odds of surveillance and ablation in all cohorts. In frail-ACCI patients who underwent surgery, RMB may provide additional risk stratification as these patients had lower rates of low-grade disease.

In solid-state chemistry, the direct reaction of elements at low temperatures is limited by low solid-state interdiffusion rates. This and the limited number of processing parameters often prevent the synthesis of metastable compounds. Precisely controlling the number of atoms and nanoarchitecture of layered elemental precursors enabled the selective synthesis of two closely related metastable tin vanadium selenides via near-diffusionless reactions at low temperatures. Although the nanoarchitectures of the precursors required to form [(SnSe 2 ) 0.80 ] 1 (VSe 2 ) 1 and [(SnSe) 1.15 ] 1 (VSe 2 ) 1 are very similar, controlling the local composition of the Sn|Se layers in the precursors enables the selective synthesis of either compound. The metastable alloy Sn x V 1- x Se 2 was preferentially formed over [(SnSe 2 ) 0.80 ] 1 (VSe 2 ) 1 , which has the identical composition, by modifying the nanoarchitecture of the precursor. Ex situ in-plane X-ray diffraction and X-ray reflectivity collected as a function of annealing temperature provided information on lateral and perpendicular growth of [(SnSe 2 ) 0.80 ] 1 (VSe 2 ) 1 . The presence of Laue oscillations throughout the self-assembly provided atomic-scale information on the thickness of the [(SnSe 2 ) 0.80 ] 1 (VSe 2 ) 1 domains, giving insights into the self-assembly process. A reaction mechanism is proposed and used to rationalize how composition and nanoarchitecture control the reaction pathway through the free energy landscape.

The number of known inorganic compounds is dramatically less than predicted due to synthetic challenges, which often constrains products to only the thermodynamically most stable compounds. Consequently, a mechanism-based approach to inorganic solids with designed structures is the holy grail of solid state synthesis. This article discusses a number of synthetic approaches using the concept of an energy landscape, which describes the complex relationship between the energy of different atomic configurations as a function of a variety of parameters such as initial structure, temperature, pressure, and composition. Nucleation limited synthesis approaches with high diffusion rates are contrasted with diffusion limited synthesis approaches. One challenge to the synthesis of new compounds is the inability to accurately predict what structures might be local free energy minima in the free energy landscape. Approaches to this challenge include predicting potentially stable compounds thorough the use of structural homologies and/or theoretical calculations. A second challenge to the synthesis of metastable inorganic solids is developing approaches to move across the energy landscape to a desired local free energy minimum while avoiding deeper free energy minima, such as stable binary compounds, as reaction intermediates. An approach using amorphous intermediates is presented, where local composition can be used to prepare metastable compounds. Designed nanoarchitecture built into a precursor can be preserved at low reaction temperatures and used to direct the reaction to specific structural homologs., (© 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Background: Firearm-related violence is a leading cause of mortality in the United States (US). Prior research suggests that public policy plays a role in firearm mortality, but the role of healthcare resources (physicians, insurance coverage) within the US policy context has not yet been studied., Objective: To examine how healthcare resources and social/firearm policy affect firearm-related suicide and homicide rates in the US., Design: Longitudinal, ecological study., Setting: US., Participants: US states from 2012 to 2016 (N = 242)., Measurement: The outcome variables were age-adjusted, firearm-related suicide and homicide rates. Predictor variables were healthcare resources (physicians, Medicaid benefits generosity) and policy context (social policy, firearm policy) with covariates for sociodemographic factors., Results: Healthcare provider variables did not have significant associations to firearm-related suicide or homicide. In fully saturated models, more worker protection laws, greater average population density, more alcohol regulation, and more firearm prohibition policies were associated with fewer firearm-related suicides. Higher generosity of Medicaid benefits was associated with fewer firearm-related homicides. Poverty rate was a predictor of both outcomes., Limitations: This state-level study cannot make individual-level inferences. Only proxy variables were available for measuring gun ownership and actual gun ownership rates may not have been ideally captured at the state level., Conclusions: At the state level, there are protective associations of certain social, healthcare, and firearm policies to firearm-related suicide and homicide rates. Healthcare resources play a role in population-level firearm outcomes but alone are not sufficient to decrease firearm-related homicide or suicide.

We argue that there is not enough evidence to safely offer focal therapy to men with Gleason grade group 3-5 prostate cancer., (Published by Elsevier B.V.)

Objectives: To create reliable predictive metrics of unilateral disease using spatial tracking from a fusion device, thereby improving patient selection for hemi-gland ablation of prostate cancer., Patients and Methods: We identified patients who received magnetic resonance imaging (MRI)/ultrasound-guided biopsy and radical prostatectomy at a single institution between 2011 and 2018. In addition to standard clinical features, we extracted quantitative features related to biopsy core and MRI target locations predictive of tumour unilaterality. Classification and Regression Tree (CART) analysis was used to create a decision tree (DT) for identifying cancer laterality. We evaluated concordance of model-determined laterality with final surgical pathology., Results: A total of 173 patients were identified with biopsy coordinates and surgical pathology available. Based on CART analysis, in addition to biopsy- and MRI-confirmed disease unilaterality, patients should be further screened for cancer detected within 7 mm of midline in a 40 mL prostate, which equates to the central third of any-sized prostate by radius. The area under the curve for this DT was 0.82. Standard diagnostics and the DT correctly identified disease laterality in 73% and 80% of patients, respectively (P = 0.13). Of the patients identified as unilateral by standard diagnostics, 47% had undetected contralateral disease or were otherwise incorrectly identified. This error rate was reduced to 17% (P = 0.01) with the DT., Conclusion: Using spatial tracking from fusion devices, a DT was more reliable for identifying laterality of prostate cancer compared to standard diagnostics. Patients with cancer detected within the central third of the prostate by radius are poor hemi-gland ablation candidates due to the risk of midline extension of tumour., (© 2019 The Authors BJU International © 2019 BJU International Published by John Wiley & Sons Ltd.)

Introduction: Positive surgical margins (PSMs) are associated with treatment failure after radical prostatectomy (RP) for patients with prostate cancer (CaP). We investigated institutional variations in PSM after RP, as well as clinical and demographic factors predicting PSM., Patients and Methods: Patients undergoing RP for clinically localized CaP were identified in the National Cancer Database in 2010 to 2013 and clinicodemographics were recorded. Treating institution was defined as academic (AMC) or nonacademic medical centers (nAMC). The primary outcome was the PSM rate. Multivariable logistic regression and propensity matching with inverse probability treatment weighing were used to both compare outcomes between AMC and nAMC and to identify predictors of PSM following RP., Results: A total of 167,260 patients met our inclusion criteria. PSM rate was significantly lower in patients treated at AMC (13,435, 18.9%) compared with 22,145 (23.0%) in those treated at nAMC (P < 0.01). The difference between PSM rate in AMC and nAMC was more pronounced in lower volume centers while it was not significant in higher volume centers. On multivariable analysis, age, race, prostate-specific antigen (PSA), biopsy Gleason score, comorbidity profile, insurance type, income, and treatment facility were significantly associated with PSM rate., Conclusion: PSM rates appear to be lower at AMC and higher volume facilities, which can potentially reflect institutional differences in surgical quality. In addition, we identified several socioeconomic and demographic factors that contribute to the likelihood of PSM following RP for localized CaP, suggesting potential systematic variation in the quality of surgical care. The cause of this variation warrants further investigation and evaluation., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objective: To evaluate the impact of frailty on adverse perioperative outcomes in patients treated with radical cystectomy for bladder cancer., Material and Methods: We identified 9459 adults (age ≥18) in the Nationwide Readmission Database who underwent radical cystectomy in 2014 for bladder cancer. We defined patients' frailty status using Johns Hopkins Adjusted Clinical Groups frailty-defining diagnosis indicator and compared in-hospital mortality, ICU-level complications, 30-day readmissions, nonhome discharge, length of hospitalization, and hospital-related costs between frail and nonfrail patients using χ 2 tests. We used multivariate logistic regression to identify predictors of the primary outcomes of interest., Results: Of 9459 patients undergoing radical cystectomy, 7.1% (n = 673) met criteria. Frail patients were more likely than nonfrail patients to have comorbid conditions (68.2% vs 59.7%; P= .005), in-hospital mortality (4.2% vs 1.5%; P= .04), ICU-level complications (52.9% vs 18.6%; P<.001), nonhome discharge (33.9% vs 11.6%; P <.001), longer length of stay (median 15 vs 7 days; P<.001), and higher median cost of the index admission ($39,665 vs $27,307). Frailty was the strongest independent predictor of ICU-level complications, nonhome discharge, increased length of stay, and hospital-related costs of any covariate., Conclusion: Frail patients receiving radical cystectomy were more likely than nonfrail patients to have adverse perioperative outcomes and higher odds of in-hospital mortality, ICU-level complications, nonhome discharge, increased length of stay, and hospital-related costs. Preoperative consideration of frailty may be useful in clinical guidance and shared decision-making., (Published by Elsevier Inc.)

Background: Hemiablation is a less morbid treatment alternative for appropriately selected patients with unilateral prostate cancer (PCa). However, to the authors' knowledge, traditional diagnostic techniques inadequately identify appropriate candidates. In the current study, the authors quantified the accuracy for identifying hemiablation candidates using contemporary diagnostic techniques, including multiparametric magnetic resonance imaging (mpMRI) and MRI-fusion with complete systematic template biopsy., Methods: A retrospective analysis of patients undergoing MRI and MRI-fusion prostate biopsy, including full systematic template biopsy, prior to radical prostatectomy in a single tertiary academic institution between June 2010 and February 2018 was performed. Hemiablation candidates had unilateral intermediate-risk PCa (Gleason score [GS] of 3+4 or 4+3, clinical T classification ≤T2, and prostate-specific antigen level <20 ng/dL) on MRI-fusion biopsy and 2) no contralateral highly or very highly suspicious Prostate Imaging Reporting and Data System version 2 (PI-RADSv2) MRI lesions. Hemiablation candidates were inappropriately selected if pathologists identified contralateral GS ≥3+4 or high-risk ipsilateral PCa on prostatectomy. The authors tested a range of hemiablation inclusion criteria and performed multivariable analysis of preoperative predictors of undetected contralateral disease., Results: Of 665 patients, 92 met primary hemiablation criteria. Of these 92 patients, 44 (48%) were incorrectly identified due to ipsilateral GS ≥3+4 tumors crossing the midline (21 patients), undetected distinct contralateral GS ≥3+4 tumors (20 patients), and/or ipsilateral high-risk PCa (3 patients) on prostatectomy. The rate of undetected contralateral disease ranged from 41% to 48% depending on inclusion criteria. On multivariable analysis, men with anterior index tumors were found to be 2.4 times more likely to harbor undetected contralateral GS ≥3+4 PCa compared with men with posterior lesions (P < .05)., Conclusions: Clinicians and patients must weigh the risk of inadequate oncologic treatment against the functional benefits of hemiablation. Further investigation into methods for improving patient selection for hemiablation is necessary., (© 2019 American Cancer Society.)

Purpose: Patients with metastatic renal cell carcinoma (mRCC) commonly present with tumor thrombi in the renal vein and inferior vena cava (IVC). The benefit of cytoreductive nephrectomy (CN) in this population is unclear and the effect on overall survival (OS) has been incompletely evaluated., Materials and Methods: We queried the National Cancer Database from 2010 to 2013 for patients diagnosed with mRCC and tumor thrombi, which was defined as renal vein, infradiaphragmatic IVC, or supradiaphragmatic IVC. Descriptive statistics were performed and associations between clinicopathologic variables and utilization of CN were analyzed. Patients were matched on the receipt of CN and Kaplan-Meier analyses and multivariable Cox proportional hazards models were used to estimate survival., Results: In total, 8,629 patients were found to have mRCC during the study period. Approximately 27% (n = 2,376) had tumor thrombus. Tumor thrombus was associated with increased rates of CN utilization, however rates decreased as thrombus level increased. In a matched Kaplan-Meier analysis, CN was associated with improved OS in patients without thrombus, and with renal vein or infradiaphragmatic thrombus (all P < 0.01). Patients with supradiaphragmatic thrombus did not benefit from CN (P = 0.46). This effect was confirmed in a Cox proportional hazards model., Conclusions: Tumor thrombus is common in patients with mRCC. OS is poor, and patient and tumor specific factors influence the use of CN. Despite discrepancies in utilization, CN is associated with improved OS, although this effect appears to be limited to those with mRCC and tumor thrombus limited to the renal vein and infradiaphragmatic IVC., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Purpose: The United States health care system is rapidly moving away from fee for service reimbursement in an effort to improve quality and contain costs. Episode based reimbursement is an increasingly relevant value based payment model of surgical care. We sought to quantify the impact of modifiable cost inputs on institutional financial margins in an episode based payment model for prostate cancer surgery., Materials and Methods: A total of 157 consecutive patients underwent robotic radical prostatectomy in 2016 at a tertiary academic medical center. We compiled comprehensive episode costs and reimbursements from the most recent urology consultation for prostate cancer through 90 days postoperatively and benchmarked the episode price as a fixed reimbursement to the median reimbursement of the cohort. We identified 2 sources of modifiable costs with undefined empirical value, including preoperative prostate magnetic resonance imaging and perioperative functional recovery counseling visits, and then calculated the impact on financial margins (reimbursement minus cost) under an episode based payment., Results: Although they comprised a small proportion of the total episode costs, varying the use of preoperative magnetic resonance imaging (33% vs 100% of cases) and functional recovery counseling visits (1 visit in 66% and 2 in 100%) reduced average expected episode financial margins up to 22.6% relative to the margin maximizing scenario in which no patient received these services., Conclusions: Modifiable cost inputs have a substantial impact on potential operating margins for prostate cancer surgery under an episode based payment model. High cost health systems must develop the capability to analyze individual cost inputs and quantify the contribution to quality to inform value improvement efforts for multiple service lines.

The examination of anisotropic nanostructures, such as wires, platelets or spikes, inside a transmission electron microscope is normally performed only in plan view. However, intrinsic defects such as growth twin interfaces could occasionally be concealed from direct observation for geometric reasons, leading to superposition. This article presents the shadow-focused ion-beam technique to prepare multiple electron-beam-transparent cross-section specimens of ZnO nanospikes, via a procedure which could be readily extended to other anisotropic structures. In contrast with plan-view data of the same nanospikes, here the viewing direction allows the examination of defects without superposition. By this method, the coexistence of two twin configurations inside the wurtzite-type structure is observed, namely and , which were not identified during the plan-view observations owing to superposition of the domains. The defect arrangement could be the result of coalescence twinning of crystalline nuclei formed on the partially molten Zn substrate during the flame-transport synthesis. Three-dimensional defect models of the twin interface structures have been derived and are correlated with the plan-view investigations by simulation., (© Niklas Wolff et al. 2019.)

Background: While genome-wide association studies (GWAS) of multiple myeloma (MM) have identified variants at 23 regions influencing risk, the genes underlying these associations are largely unknown. To identify candidate causal genes at these regions and search for novel risk regions, we performed a multi-tissue transcriptome-wide association study (TWAS)., Results: GWAS data on 7319 MM cases and 234,385 controls was integrated with Genotype-Tissue Expression Project (GTEx) data assayed in 48 tissues (sample sizes, N = 80-491), including lymphocyte cell lines and whole blood, to predict gene expression. We identified 108 genes at 13 independent regions associated with MM risk, all of which were in 1 Mb of known MM GWAS risk variants. Of these, 94 genes, located in eight regions, had not previously been considered as a candidate gene for that locus., Conclusions: Our findings highlight the value of leveraging expression data from multiple tissues to identify candidate genes responsible for GWAS associations which provide insight into MM tumorigenesis. Among the genes identified, a number have plausible roles in MM biology, notably APOBEC3C, APOBEC3H, APOBEC3D, APOBEC3F, APOBEC3G, or have been previously implicated in other malignancies. The genes identified in this TWAS can be explored for follow-up and validation to further understand their role in MM biology.

Background: Patient-reported outcomes (PROs) are a valid measure of results after revision anterior cruciate ligament (ACL) reconstruction. Revision ACL reconstruction has been documented to have worse outcomes when compared with primary ACL reconstruction. Understanding positive and negative predictors of PROs will allow surgeons to modify and potentially improve outcome for patients., Purpose/hypothesis: The purpose was to describe PROs after revision ACL reconstruction and test the hypothesis that patient- and technique-specific variables are associated with these outcomes., Study Design: Cohort study; Level of evidence, 2., Methods: Patients undergoing revision ACL reconstruction were identified and prospectively enrolled by 83 surgeons over 52 sites. Data included baseline demographics, surgical technique and pathology, and a series of validated PRO instruments: International Knee Documentation Committee (IKDC), Knee injury and Osteoarthritis Outcome Score (KOOS), Western Ontario and McMaster Universities Osteoarthritis Index, and Marx Activity Rating Scale. Patients were followed up at 2 years and asked to complete the identical set of outcome instruments. Multivariate regression models were used to control for a variety of demographic and surgical factors to determine the positive and negative predictors of PRO scores at 2 years after revision surgery., Results: A total of 1205 patients met the inclusion criteria and were successfully enrolled: 697 (58%) were male, with a median cohort age of 26 years. The median time since their most recent previous ACL reconstruction was 3.4 years. Two-year questionnaire follow-up was obtained from 989 patients (82%). The most significant positive predictors of 2-year IKDC scores were a high baseline IKDC score, high baseline Marx activity level, male sex, and having a longer time since the most recent previous ACL reconstruction, while negative predictors included having a lateral meniscectomy before the revision ACL reconstruction or having grade 3/4 chondrosis in either the trochlear groove or the medial tibial plateau at the time of the revision surgery. For KOOS, having a high baseline score and having a longer time between the most recent previous ACL reconstruction and revision surgery were significant positive predictors for having a better (ie, higher) 2-year KOOS, while having a lateral meniscectomy before the revision ACL reconstruction was a consistent predictor for having a significantly worse (ie, lower) 2-year KOOS. Statistically significant positive predictors for 2-year Marx activity levels included higher baseline Marx activity levels, younger age, male sex, and being a nonsmoker. Negative 2-year activity level predictors included having an allograft or a biologic enhancement at the time of revision surgery., Conclusion: PROs after revision ACL reconstruction are associated with a variety of patient- and surgeon-related variables. Understanding positive and negative predictors of PROs will allow surgeons to guide patient expectations as well as potentially improve outcomes.

Films containing 8, 16, 24, 32 and 64 MoSe 2 layers were synthesized using the modulated elemental reactants method. X-ray reflectivity patterns showed that the annealed films were the targeted number of MoSe 2 layers thick with atomically smooth interfaces. In-plane x-ray diffraction (XRD) scans contained only hk0 reflections for crystalline MoSe 2 monolayers. Specular XRD patterns contained only 00l reflections, also indicating that the hk0 plane of the MoSe 2 layers are parallel to the substrate. Both XRD and electron microscopy techniques indicated that the hk0 planes are rotationally disordered with respect to one another, with all orientations equally probable for large areas. The rotational disorder between MoSe 2 layers is present even when analyzed spots are within 10 nm of one another. Cross-plane thermal conductivities of 0.07-0.09 W m -1 K -1 were measured by time domain thermoreflectance, with the thinnest films exhibiting the lowest conductivity. The structural analysis suggests that the ultralow thermal conductivity is a consequence of rotational disorder, which increases the separation between MoSe 2 layers. The bonding environment of the Se atoms also becomes significantly distorted from C 3v symmetry due to the rotational disorder between layers. This structural disorder efficiently reduces the group velocity of the transverse phonon modes but not that of longitudinal modes. Since rotational disorder between adjacent layers in heterostructures is expected if the constituents have incommensurate lattices, this study indicates that these heterostructures will have very low cross-plane thermal conductivity.

Genomic regions of homozygosity (ROH), detectable in outbred populations, have been implicated as determinants of inherited risk. To examine whether ROH is associated with risk of multiple myeloma (MM), we performed whole-genome homozygosity analysis using single-nucleotide polymorphism genotype data from 2,282 MM cases and 5,197 controls, with replication in an additional 878 MM cases and 7,083 controls. Globally, the distribution of ROH between cases and controls was not significantly different. However, one ROH at chromosome 9q21, harboring the B-cell transcription factor gene KLF9, showed evidence of a consistent association and may therefore warrant further investigation as a candidate risk factor for MM. Overall, our analysis provides little support for a homozygosity signature being a significant factor in MM risk., (© 2019 The Authors. Annals of Human Genetics published by University College London (UCL) and John Wiley & Sons Ltd.)