Corrigendum to "RPN (Radius, Position of tumour, iNvasion of renal sinus) Classification and Nephrometry Scoring System: An Internationally Developed Clinical Classification To Describe the Surgical Difficulty for Renal Masses for Which Robotic Partial Nephrectomy Is Planned" [Eur. Urol. Open Sci. 54 (2023) 33-42].

[This corrects the article DOI: 10.1016/j.euros.2023.05.007.].

Clinical and functional spectrum of RAC2-related immunodeficiency.

ABSTRACT: Mutations in the small Rho-family guanosine triphosphate hydrolase RAC2, critical for actin cytoskeleton remodeling and intracellular signal transduction, are associated with neonatal severe combined immunodeficiency (SCID), infantile neutrophilic disorder resembling leukocyte adhesion deficiency (LAD), and later-onset combined immune deficiency (CID). We investigated 54 patients (23 previously reported) from 37 families yielding 15 novel RAC2 missense mutations, including one present only in homozygosity. Data were collected from referring physicians and literature reports with updated clinical information. Patients were grouped by presentation: neonatal SCID (n = 5), infantile LAD-like disease (n = 5), or CID (n = 44). Disease correlated to RAC2 activity: constitutively active RAS-like mutations caused neonatal SCID, dominant-negative mutations caused LAD-like disease, whereas dominant-activating mutations caused CID. Significant T- and B-lymphopenia with low immunoglobulins were seen in most patients; myeloid abnormalities included neutropenia, altered oxidative burst, impaired neutrophil migration, and visible neutrophil macropinosomes. Among 42 patients with CID with clinical data, upper and lower respiratory infections and viral infections were common. Twenty-three distinct RAC2 mutations, including 15 novel variants, were identified. Using heterologous expression systems, we assessed downstream effector functions including superoxide production, p21-activated kinase 1 binding, AKT activation, and protein stability. Confocal microscopy showed altered actin assembly evidenced by membrane ruffling and macropinosomes. Altered protein localization and aggregation were observed. All tested RAC2 mutant proteins exhibited aberrant function; no single assay was sufficient to determine functional consequence. Most mutants produced elevated superoxide; mutations unable to support superoxide formation were associated with bacterial infections. RAC2 mutations cause a spectrum of immune dysfunction, ranging from early onset SCID to later-onset combined immunodeficiencies depending on RAC2 activity. This trial was registered at www.clinicaltrials.gov as #NCT00001355 and #NCT00001467.

A High-Performance 3-D Imaging Technique Using Simultaneous Azimuth and Elevation Compounding.

A new technique for 3-D imaging with a row-column array (RCA) configuration has been developed. The technique requires an electrostrictive piezoelectric for the active substrate. While the top set of electrodes is connected to RF transmit and receive channels for conventional diverging wave imaging (DWI), the orthogonal bottom set of electrodes is connected to independently controlled variable dc bias channels. By implementing modulated bias patterns compounded across multiple pulses, fine delay control across the bottom elements can be achieved simultaneously with imaging with the top set of electrodes. This resulted in a high-quality two-way focus in both azimuth and elevation. A 20-MHz electrostrictive composite substrate was fabricated, and 64 top ×64 bottom electrodes were patterned and connected to custom beamforming and biasing electronics. The point spread functions were generated in all dimensions, and the -6 dB resolution was measured to be 93 [Formula: see text] axially, [Formula: see text] in the azimuth, and 328 [Formula: see text] in the elevation dimension. This was in good agreement with the simulated resolutions of 80, 273, and 280 [Formula: see text], respectively.

Consideration of Management Techniques for Advanced Hepatocellular Carcinoma With Metastasis to the Right Atrium: A Case Report.

Hepatocellular carcinoma (HCC) is a common form of cancer and the most common form of liver cancer. Multiple etiological factors leading to HCC include hepatitis B and C, diabetes, alcoholic fatty liver disease, and non-alcoholic fatty liver disease. Hepatocellular carcinoma in the late stages may present with tumor burden and thrombi that can extend into the right atrium (RA). This late-stage form of HCC has a poor prognosis. In this case, we present a 63-year-old male who presented to the hospital with acute encephalopathy with bilateral pulmonary emboli and a thrombus secondary to HCC extending into the RA. Clinical trials for non-surgical interventions are ongoing and are needed to treat patients with tumor burden who may be at bleeding risk from tumor resection.

An information theory-based approach to characterize drivers of upstream salmon migration.

The migration timing of Pacific salmon in the Columbia River basin is subject to multiple influences related to climate, human water resource management, and lagged effects such as oceanic conditions. We apply an information theory-based approach to analyze drivers of adult Chinook salmon migration within the spring and fall spawning seasons and between years based on salmon counts at dams along the Columbia and Snake Rivers. Time-lagged mutual information and information decomposition measures, which characterize lagged and nonlinear dependencies as reductions in uncertainty, are used to detect interactions between salmon counts and lagged streamflows, air and water temperatures, precipitation, snowpack, climate indices and downstream salmon counts. At a daily timescale, these interdependencies reflect migration timing and show differences between fall and spring run salmon, while dependencies based on variables at an annual resolution reflect long-term predictability. We also highlight several types of joint dependencies where predictability of salmon counts depends on the knowledge of multiple lagged sources. This study illustrates how co-varying human and natural drivers could propagate to influence salmon migration timing or overall returns, and how nonlinear types of dependencies between variables enhance predictability of a target. This information-based framework is broadly applicable to assess driving factors in other types of complex water resources systems or species life cycles.

A Real-Time Dual-Mode High-Frequency Beamformer for Ultrafast and Focused Imaging.

A firmware-based high-frequency beam- former implementing both conventional transmit focused B-mode imaging and diverging wave ultrafast (UF) imaging for Doppler overlay was developed. The beamformer can generate one transmit focused frame with four transmit focal zones (FZs), and 68 UF frames with 16 diverging waves each at a 10-Hz frame rate. The beamformer firmware stores the beamforming delays as a single bit, enabling efficient compression within the internal memory. The beamformer was characterized using a 30-MHz 64-element phased array endoscope. The hybrid system generates a 128 line by 768-pixel focused B-mode image spanning 1.2-12.6 mm axially over a ±32° range of steering angles. In addition, the system generates an UF image that is 64 lines by 384-pixels spanning 3.5-10.8 mm axially over a ±16° angle.

Trying to stomach multiple myeloma: A case report.

We report a case of a 51-year-old male with minimal past medical history who presented to his primary care provider with nausea, vomiting and constipation in the outpatient setting. Concomitantly, he was found to have a renal injury, anemia and lytic lesions which were confirmed to be due to multiple myeloma. After further investigation of the gastrointestinal symptoms, he was diagnosed with gastroparesis. This case represents an unusual presentation of gastroparesis, diagnosed at the same time as multiple myeloma, for which there has yet to be a published association. Here we detail the case, review gastric emptying physiology, the diagnostic criteria for gastroparesis and hypothesize the connection if it might have with multiple myeloma.

68Ga-PSMA-PET screening and transponder-guided salvage radiotherapy to the prostate bed alone for biochemical recurrence following prostatectomy: interim outcomes of a phase II trial.

PURPOSE: To evaluate outcomes for men with biochemically recurrent prostate cancer who were selected for transponder-guided salvage radiotherapy (SRT) to the prostate bed alone by 68Ga-labelled prostate-specific membrane antigen positron emission tomography (68Ga-PSMA-PET). METHODS: This is a single-arm, prospective study of men with a prostate-specific antigen (PSA) level rising to 0.1-2.5 ng/mL following radical prostatectomy. Patients were staged with 68Ga-PSMA-PET and those with a negative finding, or a positive finding localised to the prostate bed, continued to SRT only to the prostate bed alone with real-time target-tracking using electromagnetic transponders. The primary endpoint was freedom from biochemical relapse (FFBR, PSA > 0.2 ng/mL from the post-radiotherapy nadir). Secondary endpoints were time to biochemical relapse, toxicity and patient-reported quality of life (QoL). RESULTS: Ninety-two patients (median PSA of 0.18 ng/ml, IQR 0.12-0.36), were screened with 68Ga-PSMA-PET and metastatic disease was found in 20 (21.7%) patients. Sixty-nine of 72 non-metastatic patients elected to proceed with SRT. At the interim (3-year) analysis, 32 (46.4%) patients (95% CI 34.3-58.8%) were FFBR. The median time to biochemical relapse was 16.1 months. The rate of FFBR was 82.4% for ISUP grade-group 2 patients. Rates of grade 2 or higher gastrointestinal and genitourinary toxicity were 0% and 15.2%, respectively. General health and disease-specific QoL remained stable. CONCLUSION: Pre-SRT 68Ga-PSMA-PET scans detect metastatic disease in a proportion of patients at low PSA levels but fail to improve FFBR. Transponder-guided SRT to the prostate bed alone is associated with a favourable toxicity profile and preserved QoL. TRIAL REGISTRATION NUMBER: ACTRN12615001183572, 03/11/2015, retrospectively registered.

A Dual-Frequency Lens-Focused Endoscopic Histotripsy Transducer.

A forward-looking miniature histotripsy transducer has been developed that incorporates an acoustic lens and dual-frequency stacked transducers. An acoustic lens is used to increase the peak negative pressure through focal gain and the dual-frequency transducers are designed to increase peak negative pressure by summing the pressure generated by each transducer individually. Four lens designs, each with an f -number of approximately 1, were evaluated in a PZT5A composite transducer. The finite-element model (FEM) predicted axial beamwidths of 1.61, 2.40, 2.84, and 2.36 mm for the resin conventional, resin Fresnel, silicone conventional, and silicone Fresnel lenses, respectively; the measured axial beamwidths were 1.30, 2.28, 2.71, and 2.11 mm, respectively. Radial beamwidths from the model were between 0.32 and 0.35 mm, while measurements agreed to within 0.2 mm. The measured peak negative was 0.150, 0.124, 0.160, and 0.160 MPa/V for the resin conventional, resin Fresnel, silicone conventional, and silicone Fresnel lenses, respectively. For the dual-frequency device, the 5-MHz (therapy) transducer had a measured peak negative pressure of 0.136 MPa/V for the PZT5A composite and 0.163 MPa/V for the PMN-PT composite. The 1.2-MHz (pump) transducer had a measured peak negative pressure of 0.028 MPa/V. The pump transducer significantly lowered the cavitation threshold of the therapy transducer. The dual-frequency device was tested on an ex vivo rat brain, ablating tissue at up to 4-mm depth, with lesion sizes as small as [Formula: see text].

Atherosclerotic Cardiovascular Disease in Individuals with Hepatitis C Viral Infection.

PURPOSE OF REVIEW: Hepatitis C virus (HCV) and atherosclerotic cardiovascular disease (ASCVD) are two diseases that affect millions around the globe. Hepatitis C affects more than 70 million individuals globally. ASCVD is commonly encountered and remains the top cause of death worldwide. A link has been identified between HCV and atherosclerosis. RECENT FINDINGS: A review of recent studies which define the association between HCV infection and an increased risk of subclinical ASCVD and experiencing cardiovascular (CV) events. It is now recognized that there is an increased burden of atherosclerosis in individuals infected with HCV that translates into increased cardiovascular events. An increase in the number of diagnosed cases of HCV is expected as screening recommendations for the virus have expanded. Strategies to educate healthcare professionals about this increased CV risk will need to be considered as well as the optimal strategy to lower CV risk in this growing population.

Partial Purine Nucleoside Phosphorylase Deficiency Helps Determine Minimal Activity Required for Immune and Neurological Development.

Introduction: Complete or near complete absence of the purine nucleoside phosphorylase (PNP) enzyme causes a profound T cell immunodeficiency and neurological abnormalities that are often lethal in infancy and early childhood. We hypothesized that patients with partial PNP deficiency, characterized by a late and mild phenotype due to residual PNP enzyme, would provide important information about the minimal PNP activity needed for normal development. Methods: Three siblings with a homozygous PNP gene mutation (c.769C>G, p.His257Asp) resulting in partial PNP deficiency were investigated. PNP activity was semi-quantitively assayed by the conversion of [14C]inosine in hemolysates, mononuclear cells, and lymphoblastoid B cells. PNP protein expression was determined by Western Blotting in lymphoblastoid B cells. DNA repair was quantified by measuring viability of lymphoblastoid B cells following ionizing irradiation. Results: A 21-year-old female was referred for recurrent sino-pulmonary infections while her older male siblings, aged 25- and 28- years, did not suffer from significant infections. Two of the siblings had moderately reduced numbers of T, B, and NK cells, while the other had near normal lymphocyte subset numbers. T cell proliferations were normal in the two siblings tested. Hypogammaglobulinemia was noted in two siblings, including one that required immunoglobulin replacement. All siblings had typical (normal) neurological development. PNP activity in various cells from two patients were 8-11% of the normal level. All siblings had normal blood uric acid and increased PNP substrates in the urine. PNP protein expression in cells from the two patients examined was similar to that observed in cells from healthy controls. The survival of lymphoblastoid B cells from 2 partial PNP-deficient patients after irradiation was similar to that of PNP-proficient cells and markedly higher than the survival of cells from a patient with absent PNP activity or a patient with ataxia telangiectasia. Conclusions: Patients with partial PNP deficiency can present in the third decade of life with mild-moderate immune abnormalities and typical development. Near-normal immunity might be achieved with relatively low PNP activity.

Accounting for drivers' bicycling frequency and familiarity with bicycle infrastructure treatments when evaluating safety.

Municipalities in the United States often encourage bicycling for the health, economic, and environmental benefits by implementing new and innovative bicycle infrastructure treatments. Unfortunately, many treatments are unfamiliar to or misunderstood by drivers, especially when lacking explicit rules (e.g., shared lanes). To date, research has largely investigated bicycle infrastructure from a bicyclist's perspective, but with little research from the driver's perspective. The objective of this research is to utilize a driving simulator to investigate driver behavior towards different bicycle infrastructure treatments when driver behavior is not provoked by an interaction with bicyclists. More specifically, this research intends to investigate the impact of bicycling frequency and treatment familiarity, as well as the combined effect of the two, on driver behavior at each treatment type. The treatments investigated are shared lane markings called "sharrows", standard bike lanes, bike boxes, and merge lanes. The results show that bicycling frequency significantly affects the proportion of drivers making eye glances at treatments. In addition, drivers more familiar with bike boxes stopped significantly further back from bike boxes, and drivers more familiar with merge lanes performed the merge maneuver significantly earlier. Furthermore, driver speed and lane positioning at bike lanes was significantly affected by the combination of bike lane familiarity and bicycling frequency, but not individually. This research is a first step towards understanding driver behavior and expectation of bicyclists; an essential understanding for infrastructure treatments that do not provide physical barriers between bicycles and automobiles, and instead rely on driver behavior for safety.

Structural, functional, and behavioral insights of dopamine dysfunction revealed by a deletion in SLC6A3.

The human dopamine (DA) transporter (hDAT) mediates clearance of DA. Genetic variants in hDAT have been associated with DA dysfunction, a complication associated with several brain disorders, including autism spectrum disorder (ASD). Here, we investigated the structural and behavioral bases of an ASD-associated in-frame deletion in hDAT at N336 (∆N336). We uncovered that the deletion promoted a previously unobserved conformation of the intracellular gate of the transporter, likely representing the rate-limiting step of the transport process. It is defined by a "half-open and inward-facing" state (HOIF) of the intracellular gate that is stabilized by a network of interactions conserved phylogenetically, as we demonstrated in hDAT by Rosetta molecular modeling and fine-grained simulations, as well as in its bacterial homolog leucine transporter by electron paramagnetic resonance analysis and X-ray crystallography. The stabilization of the HOIF state is associated both with DA dysfunctions demonstrated in isolated brains of Drosophila melanogaster expressing hDAT ∆N336 and with abnormal behaviors observed at high-time resolution. These flies display increased fear, impaired social interactions, and locomotion traits we associate with DA dysfunction and the HOIF state. Together, our results describe how a genetic variation causes DA dysfunction and abnormal behaviors by stabilizing a HOIF state of the transporter.

Association of a Proactive Swallowing Rehabilitation Program With Feeding Tube Placement in Patients Treated for Pharyngeal Cancer.

Importance: A proactive speech and language pathology (SLP) program is an important component of the multidisciplinary care of patients with head and neck squamous cell carcinoma (HNSCC). Swallowing rehabilitation can reduce the rate of feeding tube placement, thereby significantly improving quality of life. Objective: To evaluate the initiation of a proactive SLP rehabilitation program at a single institution and its association with rates of feeding tube placement and dietary intake in patients with HNSCC. Design, Setting, and Participants: Cohort study at a tertiary care and referral center for patients with HNSCC serving the northern Chicago region. Patients were treated for squamous cell carcinomas of the hypopharynx, oropharynx, and nasopharynx from 2004 to 2015 with radiation or chemoradiation therapy in the definitive or adjuvant setting. Patients who received less than 5000 cGy radiation or underwent reirradiation were excluded. Interventions: A proactive SLP program for patients with HNSCC was initiated in 2011. Study cohorts were divided into 2 groups: 2004 through 2010 and 2011 through 2015. Main Outcomes and Measures: Primary outcome variables were SLP referral placement and timing of the referral. Secondary outcomes were feeding tube placement and ability to tolerate any oral intake. Results: A total of 254 patients met inclusion criteria (135 before and 119 after implementation of SLP program; median age, 60 years [range, 14-94 years]; 77% male). With the initiation of a proactive SLP program, pretreatment evaluations increased from 29 (21.5%) to 70 (58.8%; risk ratio [RR], 2.74; 95% CI, 1.92-3.91), and rate of referral overall at any time increased from 60.0% to 79.8% (RR, 1.33; 95% CI, 1.13-1.57). Feeding tube placement rates decreased from 45.9% (n = 62) to 29.4% (n = 35; RR, 0.64; 95% CI, 0.46-0.89). Among patients receiving a swallow evaluation, feeding tube requirements were less frequent for those receiving a pretreatment evaluation (31 of 99 [31%]) than for those referred during (11 of 18 [61%]) or after (38 of 59 [64%]) treatment. The rate of tolerating any oral intake at the end of treatment improved from 71.1% (n = 96) in the preimplementation period to 82.4% (n = 98; RR, 1.16; 95% CI, 1.01-1.33). Conclusions and Relevance: A proactive SLP program can be successfully established as part of the multidisciplinary care of patients with HNSCC and improve patient quality of life.

Laparoscopic lens fogging: solving a common surgical problem in standard and robotic laparoscopes via a scientific model.

BACKGROUND: Laparoscopic lens fogging (LLF) hampers vision and impedes operative efficiency. Attempts to reduce LLF have led to the development of various anti-fogging fluids and warming devices. Limited literature exists directly comparing these techniques. We constructed a model peritoneum to simulate LLF and to compare the efficacy of various anti-fogging techniques. MATERIALS AND METHODS: Intraperitoneal space was simulated using a suction bag suspended within an 8 L container of water. LLF was induced by varying the temperature and humidity within the model peritoneum. Various anti-fogging techniques were assessed including scope warmers, FREDTM, ResoclearTM, chlorhexidine, betadine and immersion in heated saline. These products were trialled with and without the use of a disposable scope warmer. Vision scores were evaluated by the same investigator for all tests and rated according to a predetermined scale. Fogging was assessed for each product or technique 30 times and a mean vision rating was recorded. RESULTS: All products tested imparted some benefit, but FREDTM performed better than all other techniques. Betadine and ResoclearTM performed no better than the use of a scope warmer alone. Immersion in saline prior to insertion resulted in decreased vision ratings. The robotic scope did not result in LLF within the model. CONCLUSIONS: In standard laparoscopes, the most superior preventative measure was FREDTM utilised on a pre-warmed scope. Despite improvements in LLF with other products FREDTM was better than all other techniques. The robotic laparoscope performed superiorly regarding LLF compared to standard laparoscope.

Erratum: Quantum State Discrimination Using the Minimum Average Number of Copies [Phys. Rev. Lett. 118, 030502 (2017)].

This corrects the article DOI: 10.1103/PhysRevLett.118.030502.

Quantum State Discrimination Using the Minimum Average Number of Copies.

In the task of discriminating between nonorthogonal quantum states from multiple copies, the key parameters are the error probability and the resources (number of copies) used. Previous studies have considered the task of minimizing the average error probability for fixed resources. Here we introduce a new state discrimination task: minimizing the average resources for a fixed admissible error probability. We show that this new task is not performed optimally by previously known strategies, and derive and experimentally test a detection scheme that performs better.