Algorithmic Midline Approach to Perineal Urethrostomy is Associated With Long-term Success and High Patient Satisfaction.

OBJECTIVE: To assess surgical success and patient-reported outcomes of perineal urethrostomy via midline approach. MATERIALS AND METHODS: Charts of patients undergoing primary perineal urethrostomy between May 2008 and June 2022 were reviewed. Background characteristics were assessed; success was defined as freedom from re-intervention. Patient-reported outcome measures were assessed using a cross-sectional phone survey. Several validated questionnaires were used to assess lower urinary tract symptoms, quality of life, and erectile dysfunction. RESULTS: Among 1768 urethroplasties performed over the study period, 103 patients (5.8%) underwent midline perineal urethrostomy. Surgery was successful in 95.1% of cases (98/103); 5 patients (4.9%) required re-intervention at a median of 8.7 months. Post-operative complications occurred in 5.8% of cases (6/103) and were both mild and self-limited. Forty-nine patients (47.6%) were reached via phone survey at a median of 61 months post-operatively. Some questions were not answered by all patients. Most patients (42/49, 86%) were satisfied or very satisfied with surgical results, and 82% (40/49) reported an improvement in their overall health. Most patients (31/41, 76%) were unbothered by sitting to urinate. Although 20% of patients (10/49) reported post-operative urinary symptoms that interfered "a lot" with their daily life, only 3 (6%) of these patients reported dissatisfaction with the outcome. Regarding sexual function, 64% (27/42) reported indifference to or increased satisfaction with sexual encounters vs before surgery. The rate of de novo erectile dysfunction was 24% (12/49). CONCLUSION: The midline approach to perineal urethrostomy provides excellent, durable success rates with high levels of patient satisfaction.

Experimental upper bounds for resonance-enhanced entangled two-photon absorption cross section of indocyanine green.

Resonant intermediate states have been proposed to increase the efficiency of entangled two-photon absorption (ETPA). Although resonance-enhanced ETPA (r-ETPA) has been demonstrated in atomic systems using bright squeezed vacuum, it has not been studied in organic molecules. We investigate for the first time r-ETPA in an organic molecular dye, indocyanine green (ICG), when excited by broadband entangled photons in near-IR. Similar to many reported virtual state mediated ETPA (v-ETPA) measurements, no r-ETPA signals are measured, with an experimental upper bound for the cross section placed at 6(±2) × 10-23 cm2. In addition, the classical resonance-enhanced two-photon absorption (r-TPA) cross section of ICG at 800 nm is measured for the first time to be 20(±13) GM, where 1 GM equals 10-50 cm4 s, suggesting that having a resonant intermediate state does not significantly enhance two-photon processes in ICG. The spectrotemporally resolved emission signatures of ICG excited by entangled photons are also presented to support this conclusion.

Ternary complexes of isopentenyl phosphate kinase from Thermococcus paralvinellae reveal molecular determinants of non-natural substrate specificity.

Isopentenyl phosphate kinases (IPKs) have recently garnered attention for their central role in biocatalytic "isoprenol pathways," which seek to reduce the synthesis of the isoprenoid precursors to two enzymatic steps. Furthermore, the natural promiscuity of IPKs toward non-natural alkyl-monophosphates (alkyl-Ps) as substrates has hinted at the isoprenol pathways' potential to access novel isoprenoids with potentially useful activities. However, only a handful of IPK crystal structures have been solved to date, and even fewer of these contain non-natural substrates bound in the active site. The current study sought to elucidate additional ternary complexes bound to non-natural substrates using the IPK homolog from Thermococcus paralvinellae (TcpIPK). Four such structures were solved, each bound to a different non-natural alkyl-P and the phosphoryl donor substrate/product adenosine triphosphate (ATP)/adenosine diphosphate (ADP). As expected, the quaternary, tertiary, and secondary structures of TcpIPK closely resembled those of IPKs published previously, and kinetic analysis of a novel alkyl-P substrate highlighted the potentially dramatic effects of altering the core scaffold of the natural substrate. Even more interesting, though, was the discovery of a trend correlating the position of two α helices in the active site with the magnitude of an IPK homolog's reaction rate for the natural reaction. Overall, the current structures of TcpIPK highlight the importance of continued structural analysis of the IPKs to better understand and optimize their activity with both natural and non-natural substrates.

Impact of COVID-19-related lifestyle changes on diabetic macular edema.

AIM: To assess diabetic macular edema (DME) progression during the early phases of the COVID-19 pandemic, when severe societal restrictions raised the concern of possible deterioration of health in patients with systemic conditions, particularly those requiring frequent office visits. METHODS: This is a multicenter retrospective chart review of 370 patients (724 eyes) with an established diagnosis of DME seen on 3 separate visits between January 2019 and July 2021. Period 1 was January 2019 to February 2020 (considered pre-COVID-19), period 2 was March 2020 to December 2020 (considered the height of the pandemic; highest level of pandemic-related clinical and societal regulations) and period 3 was January 2021 to July 2021 (re-adjustment to the new "pandemic norms"). Main outcome measures included visual acuity, body mass index (BMI), blood pressure (BP), hemoglobin A1c (HbA1c), macular thickness, patient adherence to scheduled ophthalmology visits, and DME treatment(s) received at each visit. To facilitate measurement of macular thickness, each macula was divided into 9 Early Treatment Diabetic Retinopathy Study (ETDRS)-defined macular sectors as measured by OCT imaging. RESULTS: There was no change of BMI, systolic BP, and diastolic BP between any of the time periods. HbA1c showed a very small increase from period 1 (7.6%) to period 2 (7.8%, P=0.015) and decreased back to 7.6% at period 3 (P=0.12). Macular thickness decreased for 100% of macular regions. The central macular thickness decreased across all 3 periods from 329.5 to 316.6 µm (P=0.0045). After analysis of multiple variables including HbA1c, BMI, adherence to scheduled appointments, different clinic centers, and treatment interventions, there was no easily identifiable subgroup of patients that experienced the increase in DME. CONCLUSION: DME doesn't worsen during the COVID-19 pandemic, instead sustaining a very small but statistically significant improvement. While identifying a mechanism behind our findings is beyond the scope of this study, potential explanations may include a delay in retinal changes beyond our study period, an unexpected increase in treatment frequency despite pandemic restrictions, and an unanticipated pandemic-related improvement in some lifestyle factors that may have had a positive impact on DME.

The Incidence of Pouch Neoplasia Following Ileal Pouch-Anal Anastomosis in Patients With Inflammatory Bowel Disease.

BACKGROUND: Ileal pouch-anal anastomosis (IPAA) is the standard restorative procedure following proctocolectomy in patients with inflammatory bowel disease (IBD) who require colectomy. However, removal of the diseased colon does not eliminate the risk of pouch neoplasia. We aimed to assess the incidence of pouch neoplasia in IBD patients following IPAA. METHODS: All patients at a large tertiary center with International Classification of Diseases-Ninth Revision/International Classification of Diseases-Tenth Revision codes for IBD who underwent IPAA and had subsequent pouchoscopy were identified using a clinical notes search from January 1981 to February 2020. Relevant demographic, clinical, endoscopic, and histologic data were abstracted. RESULTS: In total, 1319 patients were included (43.9% women). Most had ulcerative colitis (95.2%). Out of 1319 patients, 10 (0.8%) developed neoplasia following IPAA. Neoplasia of the pouch was seen in 4 cases with neoplasia of the cuff or rectum seen in 5 cases. One patient had neoplasia of the prepouch, pouch, and cuff. Types of neoplasia included low-grade dysplasia (n = 7), high-grade dysplasia (n = 1), colorectal cancer (n = 1), and mucosa-associated lymphoid tissue lymphoma (n = 1). Presence of extensive colitis, primary sclerosing cholangitis, backwash ileitis, and rectal dysplasia at the time of IPAA were significantly associated with increased risk of pouch neoplasia. CONCLUSIONS: The incidence of pouch neoplasia in IBD patients who have undergone IPAA is relatively low. Extensive colitis, primary sclerosing cholangitis, and backwash ileitis prior to IPAA and rectal dysplasia at the time of IPAA raise the risk of pouch neoplasia significantly. A limited surveillance program might be appropriate for patients with IPAA even with a history of colorectal neoplasia.

The incidence of pouch neoplasia in inflammatory bowel disease patients who have undergone ileal pouch­anal anastomosis (IPAA) is low. Extensive colitis, primary sclerosing cholangitis, and backwash ileitis prior to IPAA as well as rectal dysplasia at time of IPAA raise the risk of pouch neoplasia significantly.

Current opinions on the management of prolonged ischemic priapism: does penoscrotal decompression outperform corporoglanular tunneling?

Prolonged ischemic priapism presents a treatment challenge given the difficulty in achieving detumescence and effects on sexual function. To evaluate current practice patterns, an open, web-based multi-institutional survey querying surgeons' experience with and perceived efficacy of tunneling maneuvers (corporoglanular tunneling and penoscrotal decompression), as well as impressions of erectile recovery, was administered to members of societies specializing in male genital surgery. Following distribution, 141 responses were received. Tunneling procedures were the favored first-line surgical intervention in the prolonged setting (99/139, 71.2% tunneling vs. 14/139, 10.1% implant, p < .001). Although respondents were more likely to have performed corporoglanular tunneling than penoscrotal decompression (124/138, 89.9% vs. 86/137, 62.8%, p < .001), penoscrotal decompression was perceived as more effective among those who had performed both (47.3% Very or Extremely Effective for penoscrotal decompression vs. 18.7% for corporoglanular tunneling; p < .001). Many respondents who had performed both tunneling procedures felt that most regained meaningful sexual function after either corporoglanular tunneling or penoscrotal decompression (33/75, 44.0% vs. 33/74, 44.6%, p = .942). While further patient-centered investigation is warranted, this study suggests that penoscrotal decompression may outperform corporoglanular tunneling for prolonged priapism, and that recovery of sexual function may be higher than previously thought after tunneling procedures.

Investigating Deferral Rates in Cochlear Implantation: How Often Do Candidates Defer and Why?

OBJECTIVE: Evaluate the rate at which cochlear implant (CI) candidates decline surgery and identify associated factors. STUDY DESIGN: Retrospective cohort study. SETTING: Tertiary referral center. PATIENTS: Four hundred ninety-three CI candidates from July 1989 to December 2020 with complete demographic and socioeconomic data. INTERVENTIONS: Diagnostic. MAIN OUTCOME MEASURES: Age, sex, race, marital and employment status, median household income percentile, distance-to-CI-center, and residence in a medically underserved county. RESULTS: Of the 493 CI candidates included, 80 patients (16.2%) declined surgery. Based on chart checking, the most common reason patients did not receive the implant was due to loss of follow-up (38%). African American patients were 73% less likely to undergo implantation compared with White patients (odds ratio [OR], 0.27 [0.11-0.68]; p = 0.005). Asian patients were 95% less likely to undergo implantation (OR, 0.05 [0.009-0.25]; p = 0.0003) compared with White patients. For every 1-year age increase, patients were 4% less likely to undergo implantation (OR, 0.96 [0.94-0.98]; p < 0.0001) and for every 10-year age increase, the patients were 33% less likely. Compared with their single counterparts, married patients were more likely to undergo implantation (OR, 1.87 [1.12-3.15]; p = 0.02). No differences were observed when comparing implanted and nonimplanted CI candidates in sex, employment status, distance-to-CI-center, or median family income percentile. A χ2 test of independence showed no association between receiving CIs and living in medically underserved counties ( χ2 = 2; N = 493; 0.3891; p = 0.53). CONCLUSIONS: Not infrequently, CI candidates decline surgery. Although demographic factors (race, age, and marital status) were associated with the cochlear implantation decision, socioeconomic factors (median family income and residence in a medically underserved community) were not. Perhaps cultural components of a patient's race have a larger impact on whether or not the patients get implanted.

Unlocking New Prenylation Modes: Azaindoles as a New Substrate Class for Indole Prenyltransferases.

Aza-substitution, the replacement of aromatic CH groups with nitrogen atoms, is an established medicinal chemistry strategy for increasing solubility, but current methods of accessing functionalized azaindoles are limited. In this work, indole-alkylating aromatic prenyltransferases (PTs) were explored as a strategy to directly functionalize azaindole-substituted analogs of natural products. For this, a series of aza-l-tryptophans (Aza-Trp) featuring N-substitution of every aromatic CH position of the indole ring and their corresponding cyclic Aza-l-Trp-l-proline dipeptides (Aza-CyWP), were synthesized as substrate mimetics for the indole-alkylating PTs FgaPT2, CdpNPT, and FtmPT1. We then demonstrated most of these substrate analogs were accepted by a PT, and the regioselectivity of each prenylation was heavily influenced by the position of the N-substitution. Remarkably, FgaPT2 was found to produce cationic N-prenylpyridinium products, representing not only a new substrate class for indole PTs but also a previously unobserved prenylation mode. The discovery that nitrogenous indole bioisosteres can be accepted by PTs thus provides access to previously unavailable chemical space in the search for bioactive indolediketopiperazine analogs.

Efficacy of futibatinib, an irreversible fibroblast growth factor receptor inhibitor, in FGFR-altered breast cancer.

Several alterations in fibroblast growth factor receptor (FGFR) genes have been found in breast cancer; however, they have not been well characterized as therapeutic targets. Futibatinib (TAS-120; Taiho) is a novel, selective, pan-FGFR inhibitor that inhibits FGFR1-4 at nanomolar concentrations. We sought to determine futibatinib's efficacy in breast cancer models. Nine breast cancer patient-derived xenografts (PDXs) with various FGFR1-4 alterations and expression levels were treated with futibatinib. Antitumor efficacy was evaluated by change in tumor volume and time to tumor doubling. Alterations indicating sensitization to futibatinib in vivo were further characterized in vitro. FGFR gene expression between patient tumors and matching PDXs was significantly correlated; however, overall PDXs had higher FGFR3-4 expression. Futibatinib inhibited tumor growth in 3 of 9 PDXs, with tumor stabilization in an FGFR2-amplified model and prolonged regression (> 110 days) in an FGFR2 Y375C mutant/amplified model. FGFR2 overexpression and, to a greater extent, FGFR2 Y375C expression in MCF10A cells enhanced cell growth and sensitivity to futibatinib. Per institutional and public databases, FGFR2 mutations and amplifications had a population frequency of 1.1%-2.6% and 1.5%-2.5%, respectively, in breast cancer patients. FGFR2 alterations in breast cancer may represent infrequent but highly promising targets for futibatinib.

A global examination of ecological niche modeling to predict emerging infectious diseases: a systematic review.

Introduction: As emerging infectious diseases (EIDs) increase, examining the underlying social and environmental conditions that drive EIDs is urgently needed. Ecological niche modeling (ENM) is increasingly employed to predict disease emergence based on the spatial distribution of biotic conditions and interactions, abiotic conditions, and the mobility or dispersal of vector-host species, as well as social factors that modify the host species' spatial distribution. Still, ENM applied to EIDs is relatively new with varying algorithms and data types. We conducted a systematic review (PROSPERO: CRD42021251968) with the research question: What is the state of the science and practice of estimating ecological niches via ENM to predict the emergence and spread of vector-borne and/or zoonotic diseases? Methods: We searched five research databases and eight widely recognized One Health journals between 1995 and 2020. We screened 383 articles at the abstract level (included if study involved vector-borne or zoonotic disease and applied ENM) and 237 articles at the full-text level (included if study described ENM features and modeling processes). Our objectives were to: (1) describe the growth and distribution of studies across the types of infectious diseases, scientific fields, and geographic regions; (2) evaluate the likely effectiveness of the studies to represent ecological niches based on the biotic, abiotic, and mobility framework; (3) explain some potential pitfalls of ENM algorithms and techniques; and (4) provide specific recommendation for future studies on the analysis of ecological niches to predict EIDs. Results: We show that 99% of studies included mobility factors, 90% modeled abiotic factors with more than half in tropical climate zones, 54% modeled biotic conditions and interactions. Of the 121 studies, 7% include only biotic and mobility factors, 45% include only abiotic and mobility factors, and 45% fully integrated the biotic, abiotic, and mobility data. Only 13% of studies included modifying social factors such as land use. A majority of studies (77%) used well-recognized ENM algorithms (MaxEnt and GARP) and model selection procedures. Most studies (90%) reported model validation procedures, but only 7% reported uncertainty analysis. Discussion: Our findings bolster ENM to predict EIDs that can help inform the prevention of outbreaks and future epidemics. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier (CRD42021251968).

Entangled Photon Correlations Allow a Continuous-Wave Laser Diode to Measure Single-Photon, Time-Resolved Fluorescence.

Fluorescence lifetime experiments are a standard approach for measuring excited-state dynamics and local environmental effects. Here, we show that entangled photon pairs produced from a continuous-wave (CW) laser diode can replicate pulsed laser experiments without phase modulation. As a proof of principle, picosecond fluorescence lifetimes of indocyanine green are measured in multiple environments. The use of entangled photons has three unique advantages. First, low-power CW laser diodes and entangled photon source design lead to straightforward on-chip integration for a direct path to distributable fluorescence lifetime measurements. Second, the entangled pair's wavelength is easily tuned by adjusting the temperature or electric field, allowing a single source to cover octave bandwidths. Third, femtosecond temporal resolutions can be reached without requiring major advances in source technology or external phase modulation. Entangled photons could therefore provide increased accessibility to time-resolved fluorescence while also opening new scientific avenues in photosensitive and inherently quantum systems.

Adavosertib Enhances Antitumor Activity of Trastuzumab Deruxtecan in HER2-Expressing Cancers.

PURPOSE: Cyclin E (CCNE1) has been proposed as a biomarker of sensitivity to adavosertib, a Wee1 kinase inhibitor, and a mechanism of resistance to HER2-targeted therapy. EXPERIMENTAL DESIGN: Copy number and genomic sequencing data from The Cancer Genome Atlas and MD Anderson Cancer Center databases were analyzed to assess ERBB2 and CCNE1 expression. Molecular characteristics of tumors and patient-derived xenografts (PDX) were assessed by next-generation sequencing, whole-exome sequencing, fluorescent in situ hybridization, and IHC. In vitro, CCNE1 was overexpressed or knocked down in HER2+ cell lines to evaluate drug combination efficacy. In vivo, NSG mice bearing PDXs were subjected to combinatorial therapy with various treatment regimens, followed by tumor growth assessment. Pharmacodynamic markers in PDXs were characterized by IHC and reverse-phase protein array. RESULTS: Among several ERBB2-amplified cancers, CCNE1 co-amplification was identified (gastric 37%, endometroid 43%, and ovarian serous adenocarcinoma 41%). We hypothesized that adavosertib may enhance activity of HER2 antibody-drug conjugate trastuzumab deruxtecan (T-DXd). In vitro, sensitivity to T-DXd was decreased by cyclin E overexpression and increased by knockdown, and adavosertib was synergistic with topoisomerase I inhibitor DXd. In vivo, the T-DXd + adavosertib combination significantly increased γH2AX and antitumor activity in HER2 low, cyclin E amplified gastroesophageal cancer PDX models and prolonged event-free survival (EFS) in a HER2-overexpressing gastroesophageal cancer model. T-DXd + adavosertib treatment also increased EFS in other HER2-expressing tumor types, including a T-DXd-treated colon cancer model. CONCLUSIONS: We provide rationale for combining T-DXd with adavosertib in HER2-expressing cancers, especially with co-occuring CCNE1 amplifications. See related commentary by Rolfo et al., p. 4317.

Surgical Management of Male Stress Incontinence: Techniques, Indications, and Pearls for Success.

Purpose: Male stress urinary incontinence (SUI) has detrimental and long-lasting effects on patients. Management of this condition is an evolving field with multiple options for surgical treatment. We sought to review the pre-operative evaluation, intra-operative considerations, post-operative care, and future directions for treatment of male SUI. Methods: A literature review was performed using the PubMed platform to identify peer-reviewed, English-language articles published within the last 5 years pertaining to management of male stress urinary incontinence with an emphasis on devices currently on the market in the United States including the artificial urinary sphincter (AUS), male urethral slings, and the ProACTTM system. Patient selection criteria, success rates, and complications were compared between the studies. Results: Twenty articles were included in the final contemporary review. Pre-operative workup most commonly included demonstration of incontinence, PPD, and cystoscopy. Definition of success varied by study; the most common definition used was social continence (0-1 pads per day). Reported rates of success were higher for the AUS than for male urethral slings (73-93% vs 70-90%, respectively). Complications for these procedures include urinary retention, erosions, infections, and device malfunction. Newer treatment options including adjustable balloon systems and adjustable slings show promise but lack long-term follow-up. Conclusion: Patient selection remains the primary consideration for surgical decision-making for management of male SUI. The AUS continues to be the gold standard for moderate-to-severe male SUI but comes with inherent risk of need for revision. Male slings may be a superior option for appropriately selected men with mild incontinence but are inferior to the AUS for moderate and severe incontinence. Ongoing research will shed light on long-term results for newer options such as the ProACT and REMEEX systems.

Mechanical indications for inflatable penile prosthesis revision: analysis and implications for revision surgery.

BACKGROUND: Despite technical advancements, inflatable penile prostheses (IPPs) are inherently at risk of mechanical failure given their nature as hydraulic devices. AIM: To characterize IPP component failure location at the time of device revision and stratify by manufacturer: American Medical Systems (Boston Scientific [BSCI]) and Coloplast (CP). METHODS: A retrospective review of penile prosthesis cases from July 2007 to May 2022 was conducted, identifying men who underwent revision surgery. Cases were excluded if documentation did not denote the cause of failure or the manufacturer. Mechanical indications for surgery were categorized by location (eg, tubing, cylinder, or reservoir leak; pump malfunction). Nonmechanical revisions were excluded (component herniation, erosion, or crossover). Categorical variables were assessed with Fisher exact or chi-square analysis; Student t-test and Mann-Whitney U test were used for continuous variables. OUTCOMES: Primary outcomes included specific location of IPP mechanical failure among BSCI and CP devices and time to mechanical failure. RESULTS: We identified 276 revision procedures, 68 of which met inclusion criteria (46 BSCI and 22 CP). Revised CP devices were longer than BSCI devices (median cylinder length, 20 vs 18 cm; P < .001). Log-rank analysis revealed a similar time to mechanical failure between brands (P = .096). CP devices failed most often due to tubing fracture (19/22, 83%). BSCI devices had no predominant site of failure. Between manufacturers, tubing failure was more common in CP devices (19/22 vs 15/46 for BSCI, P < .001), while cylinder failure was more common among BSCI devices (10/46 vs 0/22 for CP, P = .026). CLINICAL IMPLICATIONS: The distribution of mechanical failure is significantly different between BSCI and CP devices; this has implications regarding the approach to revision surgery. STRENGTHS AND LIMITATIONS: This is the first study to directly compare when and where mechanical failure occurs in IPPs and to compare the 2 main manufacturers head-to-head. This study would be strengthened by being repeated in a multi-institutional fashion to provide more robust and objective evaluation. CONCLUSION: CP devices commonly failed at the tubing and rarely elsewhere, while BSCI devices showed no predominant failure site; these findings may inform decision making regarding revision surgery.

Delayed or Forgone Healthcare Due to COVID-19 among Adults with Vision Impairment.

INTRODUCTION: Decreased public transit, no­visitor policies, and other restrictions to reduce the spread of COVID­19 may limit healthcare access for vision impaired adults. This study aimed to assess rates of healthcare delayed or forgone due to COVID­19 among adults with low vision. METHODS: Data were analyzed from the 2021 National Health Interview Survey, a representative sample of US adults. Vision and hearing impairment were determined by self­report. The primary study outcome was delayed or canceled medical care due to COVID­19. Multivariable logistic regression models adjusted for gender, age, race, education, insurance, income, region, and chronic comorbidities were constructed to examine associations of medical care delayed due to COVID­19. RESULTS: Overall, 1.6% (n=457) of adults had vision impairment and 1.6% (n=438) had hearing impairment. Vision impairment was not associated with having taken a COVID­19 test (P=0.34) or previous COVID­19 infection (P=0.46). Adults with vs without low vision had higher rates of delayed (30.7% vs 19.2%, 1.86 [1.43-2.42], P<.0001) and cancelled care due to COVID-19 (23.9% vs 12.2%, 2.21 [1.66-2.94], P<.0001). Even compared to adults with hearing impairment, those with vision impairment were more likely to report canceled medical care due to COVID­19 (1.20 [1.02-1.41], P=0.03). CONCLUSION: Adults with low vision had increased risk of delayed and canceled medical care due to COVID­19, with increased rates of canceled medical care even when compared to those with hearing impairment. These results suggest COVID­19 and interventions to limit its spread have had a disproportionate impact on adults with low vision and place them at risk of poor health outcomes.

A procedure for predicting, illustrating, communicating, and optimizing patient-centered outcomes of epilepsy surgery using nomograms and Bayes' theorem.

Clinicians have an ethical obligation to obtain and convey relevant information about possible treatment outcomes in a manner that can be comprehended by patients. This contributes to the processes of informed consent and shared prospective decision-making. In epilepsy neurosurgery, there has historically been an emphasis on studying clinician-centered (e.g., seizure- and cognition-related) outcomes and using these data to inform recommendations and, by extension, to frame pre-surgical counseling with respect to patients' decisions about elective neurosurgery. In contrast, there is a relative dearth of available data related to patient-centered outcomes of epilepsy neurosurgery, such as functional (e.g., employment) status, and there is also a lack of methods to communicate these data to patients. Here, illustrated using a hypothetical case scenario, we present a potential solution to the latter of these problems using principles of evidence-based neuropsychology; published data on patient employment status before and after epilepsy neurosurgery; and Bayes' theorem. First, we reviewed existing literature on employment outcomes following epilepsy neurosurgery to identify and extract data relevant to our hypothetical patient, clinical question, and setting. Then, we used the base rate (prior probability) of post-surgical unemployment, contingency tables (to derive likelihood ratios), and Bayes' theorem to compute the conditional (posterior) probability of post-surgical employment status for our hypothetical patient scenario. Finally, we translated this information to an intuitive visual format (Bayesian nomogram) that can support evidence-based pre-surgical counseling. We propose that the application of our patient-centered decision-support process and visual aid will improve clinician-patient communication about prospective risks and benefits of epilepsy neurosurgery and will empower clinicians and patients to make informed decisions about whether or not to pursue elective neurosurgery with a greater degree of confidence and with more realistic and concrete expectations about possible outcomes. We further propose that clinicians and patients would benefit from incorporating this evidence-based framework into a broader sequence of function-focused epilepsy treatment that includes pre-surgical assessments and interventions ("prehabilitation"), neurosurgery, and post-surgical cognitive/vocational rehabilitation.

Single-Photon Scattering Can Account for the Discrepancies among Entangled Two-Photon Measurement Techniques.

Entangled photon pairs are predicted to linearize and increase the efficiency of two-photon absorption, allowing continuous wave laser diodes to drive ultrafast time-resolved spectroscopy and nonlinear processes. Despite a range of theoretical studies and experimental measurements, inconsistencies in the value of the entanglement-enhanced interaction cross section persist. A spectrometer that can temporally and spectrally characterize the entangled photon state before, during, and after any potential two-photon excitation event is constructed. For the molecule rhodamine 6G, which has a virtual state pathway, any entangled two-photon interaction is found to be equal to or weaker than classical, single-photon scattering events. This result can account for the discrepancies among the wide variety of entangled two-photon absorption cross sections reported from different measurement techniques. The reported instrumentation can unambiguously separate classical and entangled effects and therefore is important for the growing field of nonlinear and multiphoton entangled spectroscopy.

Requirements and expectations of high-quality biomarkers for atopic dermatitis and psoriasis in 2021-a two-round Delphi survey among international experts.

BACKGROUND: Chronic inflammatory skin diseases such as atopic dermatitis (AD) and psoriasis (PSO) present major challenges in health care. Thus, biomarkers to identify disease trajectories and response to treatments to improve the lives of affected individuals warrant great research consideration. The requirements that these biomarkers must fulfil for use as practical clinical tools have not yet been adequately investigated. AIM: To identify the core elements of high-quality AD and PSO biomarkers to prepare recommendations for current biomarker research. METHOD: A cross-sectional two-round Delphi survey was conducted from August to October 2019 and October to November 2020. All participants were members of the BIOMAP project, an EU-funded consortium of clinicians, researchers, patient organizations and pharmaceutical industry partners. The first round consisted of three open-ended questions. Responses were qualitatively analysed, and 26 closed statements were developed. For the second round, 'agreement' was assumed when the responses of ≥70% of the participants were ≥5 points on a 7-point Likert scale for each statement. Priority classification was based on mean scores (<20th percentile = low, 20th to 60th percentile = medium, >60th percentile = high). RESULTS: Twenty-one and twenty-six individuals participated in rounds one and two, respectively. From 26 statements that were included in round 2, 18 achieved agreement (8 concerning the performance, 8 for the purpose and 2 on current obstacles). Seven statements were classified as high priority, e.g. those concerning reliability, clinical validity, a high positive predictive value, prediction of the therapeutic response and disease progression. Another seven statements were assigned medium priority, e.g. those about analytical validity, prediction of comorbidities and therapeutic algorithm. Low priority included four statements, like those concerning cost effectiveness and prediction of disease flares. CONCLUSION: The core requirements that experts agreed on being essential for high-quality AD and PSO biomarkers require rapid validation. Biomarkers can therefore be assessed based on these prioritized requirements.

Energy Expenditure of Female International Standard Soccer Players: A Doubly Labeled Water Investigation.

PURPOSE: The purpose of this study is to quantify total daily energy expenditure (TEE) of international adult female soccer players. METHODS: Twenty-four professional players were studied during a 12-d period where they participated in an international training camp (also inclusive of two competitive games) representing the English national team. The TEE was assessed via the doubly labeled water method during the full 12 d as well as the initial 4-d period before game one. Energy intake was also assessed (via weighed food analysis) during the initial 4-d period to permit estimation of energy availability (EA). RESULTS: Mean TEE did not differ (P = 0.31) between the 12-d (2693 ± 432 kcal·d-1; range, 2105-3507 kcal·d-1; 54 ± 6 kcal·kg-1 fat-free mass [FFM]) versus the 4-d assessment period (2753 ± 359 kcal·d-1; range, 1942-3280 kcal·d-1; 56 ± 8 kcal·kg-1 FFM). Mean 4-d energy intake was 1923 ± 357 kcal·d-1 (range, 1639-2172 kcal·d-1) and mean activity energy expenditure was 1069 ± 278 kcal·d-1 (range, 155-1549 kcal·d-1). When assessed for estimated EA, 88% of players were categorized with low EA status according to the threshold of <30 kcal·kg-1 FFM. Mean daily carbohydrate intake equated to 3.3 ± 0.7 g·kg-1 body mass. CONCLUSIONS: When compared with previously published data from adult male players, we demonstrate that the relative daily energetic requirements of engaging in professional soccer training and match play are comparable between sexes. From a practical perspective, data suggest that practitioners should likely focus education and behavior change strategies on "fuelling" for match play and training to optimize both player health and performance.