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Abstract The development of a basin‐specific comprehensive flood record using publicly available data for the James River Basin, Virginia. Using mixed surface analysis maps (NOAA, NWS), historical hurricane records (IBTrACS, HURDAT2), and flood and river gauge records (NWS, USGS), a database is created for analysis. Related to creating this database, a novel classification of six unique weather systems (non‐tropical and tropical) responsible for flooding is presented. The analysis includes Two‐Way tables with observed marginal and joint probabilities in various potential flood, storm, and regional combinations. Results show 233 tropical systems passed within the 500‐km study area, with 12.4%, or 29 systems of those systems causing flooding within the basin. An additional 713 events were non‐tropical, composing the majority of flood sources in the basin. Non‐tropical systems are responsible for 84% of the worst floods recorded, leading to an increased frequency of 6% yearly since 1941 and nearly 770% between 2014 and 2018. The findings of this study will be the basis for assessing land use and population patterns in the area, along with a future compound flooding model for the lower James River Basin.

It is believed that DNA double-strand breaks induced by Zika virus (ZIKV) infection in pregnant women is a main reason of brain damage (e.g. microcephaly, severe brain malformation, and neuropathy) in newborn babies [1,2], but its underlying mechanism is poorly understood. In this study, we report that the depletion of ERp57, a member of the protein disulphide isomerase (PDI) family, leads to the limited production of ZIKV in nerve cells. ERp57 knockout not only suppresses viral induced reactive oxygen species (ROS) mediated host DNA damage, but also decreases apoptosis. Strikingly, DNA damage depends on ERp57-bridged complex formation of viral protein NS2B/NS3. LOC14, an ERp57 inhibitor, restricts ZIKV infection and virus-induced DNA damage. Our work reveals an important role of ERp57 in both ZIKV propagation and virus-induced DNA damage, suggesting a potential target against ZIKV infection.

Purpose: This study aims to examine predisposing anatomic factors and subsequent post-decompression functional outcomes among high-intensity athletes with thoracic outlet syndrome (TOS). Materials and Methods : A single-institution retrospective review was performed on a prospective database of patients with TOS from 2018 to 2023 who had undergone operative decompression for TOS. Demographics, TOS characteristics, predisposing anatomy, operative details, and postoperative outcomes were examined. The primary outcome was postoperative return to sport. Secondary outcomes included vascular patency. Results : A total of 13 patients who were engaged in high-demand athletic activity at the time of their diagnosis were included. Diagnoses included 8 (62%) patients with venous TOS, 4 (31%) patients with neurogenic TOS, and 1 (8%) patient with arterial TOS. Mixed vascular and neurogenic TOS was observed in 3 (23%) patients. The mean age of the cohort was 30 years. Abnormal scalene structure was observed in 12 (92%) patients, and abnormal bone structures were noted in 4 (27%) patients; 2 (15%) with cervical ribs and 3 (23%) patients with clavicular abnormalities. Prior ipsilateral upper extremity trauma was reported in 4 (27%) patients. Significant joint hypermobility was observed in 8 (62%) patients with a median Beighton score of 6. Supraclavicular cervical and/or first rib resection with scalenectomy was performed in all patients. One case of postoperative pneumothorax was treated non-operatively. Ten (77%) patients returned to sport. Duplex ultrasonography showed subclavian vein patency in all 8 patients with venous TOS and wide patency with no drop in perfusion indices in the patient with arterial TOS. Conclusion : Athletes with TOS who required operative intervention had a high incidence of musculoskeletal aberrations and joint hypermobility. Supraclavicular decompression was associated with a high success rate, with overall good functional outcomes and good likelihood of patients returning to preoperative high-intensity athletics.

We describe the case of a 62-year-old man presenting 2 months after a reversed great saphenous vein femoropopliteal bypass performed for critical limb ischemia. He was found to have early, high-grade bypass graft stenosis on duplex ultrasound. Subsequent angiography demonstrated flow limitations secondary to two areas of retained venous valves in the proximal and mid-portions of the vein graft. The culprit valve lesions were successfully lysed endovascularly with a HawkOne (Medtronic) directional atherectomy device. This case demonstrates a safe, novel use of a directional atherectomy device for treatment of remnant valves causing hemodynamically significant flow problems in peripheral vein grafts.

Purpose: To identify demographic trends of foreign object genital injuries presenting to emergency departments from 2011 to 2020. Materials and Methods: The National Electronic Injury Surveillance System database reports consumer product-related injuries in United States ED visits. The database was queried to identify 375 cases of genital injuries from 2011 to 2020. Inclusion criteria consisted of cases reporting injuries involving the urethra, penis, or scrotum. Data was reported and analyzed using linear regression. Results: Based on 375 cases, an estimated 13,170 (95% confidence interval, 10,817–15,522) patients in the US suffered genital injuries due to foreign bodies between 2011 and 2020. These injuries involved the penis (65.9%), urethra (30.7%) and scrotum (3.5%). Of all patients, 11.8% required hospital admission after treatment of which injuries to the urethra were most common (44.0%). Most of these patients were ages 19 to 64 (66.1%). Consumer products most implicated included rings (50.7%), zippers (17.1%), and pens and pencils (10.3%). Injuries due to zippers and swimming apparel occurred significantly more frequently in patients ages 0–18 (p

Chromophobe renal cell carcinoma (chRCC) is one of the less common types of kidney cancer and generally portends a more favorable prognosis. RCC with sarcomatoid differentiation has a more aggressive clinical course with poor outcomes. Four cases of chRCC with varying degrees of sarcomatoid differentiation were retrospectively reviewed at our institution, and clinicopathologic data as well as clinical courses were reported. Patients with higher degrees of sarcomatoid differentiation and larger tumors at presentation generally had and worse overall survival. chRCC with sarcomatoid differentiation portends a poor prognosis with limited data on systemic treatment options for metastatic disease.

Abstract Background Treatment of chronic illness accounts for over 90% of Medicare spending. Chronic lymphedema places 3–10 million Americans at risk for recurrent cellulitis. Without convincing predictions of the costs and benefits of lymphedema treatment, insurers are reluctant to fully cover treatment of this common condition. Earlier papers discussed the costs and benefits of the first 5, 7, and 10 years of a lymphedema treatment mandate in Virginia. This paper updates these costs and benefits to 16 years of experience, and includes the impacts of the Patient Protection and Affordable Care Act of 2010 and the transition to ICD-10-CM diagnostic codes in 2015. It provides added confidence that costs of a lymphedema treatment mandate are reasonable, and can result in health insurance contract savings for reduced medical visits and hospitalizations for lymphedema patients. Methods Virginia requires annual reporting of the segregated costs of each of its 30 medical mandates. Data on Virginia’s lymphedema treatment mandate for the years 2004 to 2019 have been collected from the series of annual reports. These data include actual lymphedema treatment claims data, utilization data, and claims-based estimates of the premium impact. Results The average actual lymphedema claim cost was $2.03 per individual contract and $3.54 per group contract for the years reported, representing 0.05 and 0.08% of average total claims. The estimated premium impact was 0.16–0.32% of total average premium for all mandated coverage contracts. While lymphedema claim costs increased 3–6% per year over the study period, generally following the rise of health care costs, claim costs as a percent of average contract claims fell at a rate of 1.26–1.52% per year over that period. Medical office visits for lymphedema-related services fell from 0.10 to 0.02 visits per year per contract from the beginning to the end of the study period, and hospitalizations for lymphedema or lymphedema-related cellulitis fell to almost zero. Conclusions The Virginia data confirmed previous conclusions that the costs of treatment of lymphedema are a small part of a typical health insurance contract, and that treatment of lymphedema by managing swelling results in lower overall medical costs and fewer hospitalizations. This is a potent model for reduction in healthcare costs while improving the quality of care for cancer survivors and others suffering with this chronic progressive condition.

A 37-year-old male with a history of chronic nephrolithiasis presented to the ED with gross hematuria, clot retention, and right flank pain. The patient had radiological findings of perinephric stranding, marked hydronephrosis, and marked thinning of the right renal parenchyma on computed tomography (CT), all suggestive of xanthogranulomatous pyelonephritis (XGP). The specimen following radical nephrectomy revealed urothelial carcinoma (UC) in a background of XGP but with no evidence of spread to regional lymph nodes. Follow-up imaging revealed hypodense lesions in the liver which demonstrated UC on biopsy. This is the first reported case of a young patient presenting with such an advanced stage of UC in the setting of XGP. It illustrates the link between inflammatory processes of the kidney and malignancy of the upper urinary tract.

Rising sea level in the next century exposes the Ports of Los Angeles and Long Beach to higher hazards from Alaskan tsunamis. By 2100, waves generated by an M8 Alaskan earthquake cause similar impacts in California to waves from an Alaskan M9 today.

Adult (3 month) mice with cardiac-specific overexpression of adenylyl cyclase (AC) type VIII (TGAC8) adapt to an increased cAMP-induced cardiac workload (~30% increases in heart rate, ejection fraction and cardiac output) for up to a year without signs of heart failure or excessive mortality. Here, we show classical cardiac hypertrophy markers were absent in TGAC8, and that total left ventricular (LV) mass was not increased: a reduced LV cavity volume in TGAC8 was encased by thicker LV walls harboring an increased number of small cardiac myocytes, and a network of small interstitial proliferative non-cardiac myocytes compared to wild type (WT) littermates; Protein synthesis, proteosome activity, and autophagy were enhanced in TGAC8 vs WT, and Nrf-2, Hsp90α, and ACC2 protein levels were increased. Despite increased energy demands in vivo LV ATP and phosphocreatine levels in TGAC8 did not differ from WT. Unbiased omics analyses identified more than 2,000 transcripts and proteins, comprising a broad array of biological processes across multiple cellular compartments, which differed by genotype; compared to WT, in TGAC8 there was a shift from fatty acid oxidation to aerobic glycolysis in the context of increased utilization of the pentose phosphate shunt and nucleotide synthesis. Thus, marked overexpression of AC8 engages complex, coordinate adaptation "circuity" that has evolved in mammalian cells to defend against stress that threatens health or life (elements of which have already been shown to be central to cardiac ischemic pre-conditioning and exercise endurance cardiac conditioning) that may be of biological significance to allow for proper healing in disease states such as infarction or failure of the heart.

Low availability of sustainable biomass prevents transition of district heating in Europe away from fossil fuels. The need for sustainable fuels stems from current energy generation structure, which mainly relies on centralised combined heat and power operated as baseload units. Our study shows that districts with generation of renewable power, heat and synthetic natural gas can reach complete energy system decarbonisation even without biomass, only using wind and solar power as primary energy. It requires rethinking of interactions between electricity, gas and heating networks and a polygeneration solution with power-to-heat and power-to-gas technologies to fully utilise local solar and wind power and cover peak demands. Power-to-heat as baseload units supported with power-to-gas for seasonal and back-up energy storage are proposed as novel district heating approach. The operation of such polygeneration is tested successfully using a model of a Finnish district. Carbon dioxide circulation is analysed together with capacity requirements to synthetic natural gas and needed wind power installation. Resulting complete decarbonisation requires coordination and flexible operation of power-to-heat and power-to-gas capacity together with gas-fired combined heat and power plants and heat-only boilers, which ensures that renewable power production, heating and power needs, security of supply and grid limitations are met.

The hazard from earthquake-generated tsunami waves is not only determined by the earthquake’s magnitude and mechanisms, and distance to the earthquake area, but also by the geomorphology of the nearshore and onshore areas, which can change over time. In coastal hazard assessments, a changing coastal environment is commonly taken into account by increasing the sea-level to projected values (static). However, sea-level changes and other climate-change impacts influence the entire coastal system causing morphological changes near- and onshore (dynamic). We compare the run-up of the same suite of earthquake-generated tsunamis to a barrier island-marsh-lagoon-marsh system for statically adjusted and dynamically adjusted sea level and bathymetry. Sea-level projections from 2000 to 2100 are considered. The dynamical adjustment is based on a morphokinetic model that incorporates sea-level along with other climate-change impacts. We employ Representative Concentration Pathways 2.6 and 8.5 without and with treatment of Antarctic Ice-sheet processes (known as K14 and K17) as different sea-level projections. It is important to note that we do not account for the occurrence probability of the earthquakes. Our results indicate that the tsunami run-up hazard for the dynamic case is approximately three times larger than for the static case. Furthermore, we show that nonlinear and complex responses of the barrier island-marsh-lagoon-marsh system to climate change profoundly impacts the tsunami hazard, and we caution that the tsunami run-up is sensitive to climate-change impacts that are less well-studied than sea-level rise.

Abstract Boulders are excellent candidate deposits to study coastal inundation events by storms and tsunamis due to their significant preservation potential. However, it is difficult to infer how and what forcing dislodged the boulder. We present a new model that enables ensemble and Monte‐Carlo‐type simulations to study the sensitivity of boulder, the fluid flow, and environmental parameters. Our examples show that boulder transport is complex and nonlinear, and to acknowledge the uncertainties of the boulder's preexisting transport conditions, a range of velocities and environmental parameters should be used to quantify the flow that caused boulder dislodgement.

Introduction Opioid agonist treatment is effective for opioid dependence and newer extended-release buprenorphine (BUP-XR) injections represent a significant development. The Community Long-Acting Buprenorphine (CoLAB) study aims to evaluate client outcomes among people with opioid dependence receiving 48 weeks of BUP-XR treatment, and examines the implementation of BUP-XR in diverse community healthcare settings in Australia.Methods and analysis The CoLAB study is a prospective single-arm, multicentre, open-label trial of monthly BUP-XR injections in people with opioid dependence. Participants are being recruited from a network of general practitioner and specialist drug treatment services located in the states of New South Wales, Victoria and South Australia in Australia. Following a minimum 7 days on 8–32 mg of sublingual buprenorphine (±naloxone), participants will receive monthly subcutaneous BUP-XR injections administered by a healthcare practitioner at intervals of 28 days (−2/+14 days). The primary endpoint is participant retention in treatment at 48 weeks after treatment initiation. Secondary endpoints will evaluate dosing schedule variations, craving, withdrawal, substance use, health and well-being, and client-reported treatment experience. Qualitative and costing substudies will examine implementation barriers and facilitators at the client and provider level.Ethics and dissemination The study has received ethics approval from the St Vincent’s Hospital Sydney Human Research Ethics Committee (Ref. HREC/18/SVH/221). The findings will be disseminated via publication in peer-reviewed journals, presentations at national and international scientific conferences, and in relevant community organisation publications and forums.Trial registration number NCT03809143Protocol identifier CoLAB1801, V.4.0 dated 01 August 2019

Coastal boulder deposits (CBD), transported by waves at elevations above sea level and substantial distances inland, are markers for marine incursions. Whether they are tsunami or storm deposits can be difficult to determine, but this is of critical importance because of the role that CBD play in coastal hazard analysis. Equations from seminal work by Nott (1997), here referred to as the Nott Approach, are commonly employed to calculate nominal wave heights from boulder masses as a means to discriminate between emplacement mechanisms. Systematic review shows that this approach is based on assumptions that are not securely founded and that direct relationships cannot be established between boulder measurements and wave heights. A test using an unprecedented dataset of boulders moved by storm waves (with associated sea-state data) shows a lack of agreement between calculations and actual wave heights. The equations return unrealistically large heights, many of which greatly exceed sea states occurring during the boulder-moving storms. This underscores the finding that Nott-Approach wave-height calculations are unreliable. The result is general, because although the field data come from one region (the Aran Islands, Ireland), they represent a wide range of boulder masses and topographic settings and present a valid test of hydrodynamic equations. This analysis demonstrates that Nott Approach equations are incapable of distinguishing storm waves from tsunami transport and that wave heights hindcast from boulder masses are not meaningful. Current hydrodynamic understanding does not permit reliable computation of wave height from boulder measurements. A combination of field, numerical, and experimental approaches is required to quantify relationships between wave power and mass transport onshore. Many CBD interpreted as tsunami deposits based on Nott-Approach analysis may in fact have been emplaced during storms and should therefore be re-evaluated. This is especially important for CBD that have been incorporated into long-term coastal risk assessments, which are compromised if the CBD are misinterpreted. CBD dynamics can be better determined from a combination of detailed field measurements, modeling, and experiments. A clearer understanding of emplacement mechanisms will result in more reliable hazard analysis.

Consistent calibration and monitoring is a basic prerequisite for providing a reliable time series of global and regional sea-level variations from altimetry. The precisions of sea-level measurements and regional biases for six altimeter missions (Jason-1/2/3, Envisat, Saral, Sentinel-3A) are assessed in this study at 11 GNSS-controlled tide gauge stations in the German Bight (SE North Sea) for the period 2002 to 2019. The gauges are partly located at the open water, and partly at the coast close to mudflats. The altimetry is extracted at virtual stations with distances from 2 to 24 km from the gauges. The processing is optimized for the region and adjusted for the comparison with instantaneous tide gauge readings. An empirical correction is developed to account for mean height gradients and slight differences of the tidal dynamics between the gauge and altimetry, which improves the agreement between the two data sets by 15–75%. The precision of the altimeters depends on the location and mission and ranges from 1.8 to 3.7 cm if the precision of the gauges is 2 cm. The accuracy of the regional mission biases is strongly dependent on the mean sea surface heights near the stations. The most consistent biases are obtained based on the CLS2011 model with mission-dependent accuracies from 1.3 to 3.4 cm. Hence, the GNSS-controlled tide gauges operated operationally by the German Waterway and Shipping Administration (WSV) might complement the calibration and monitoring activities at dedicated CalVal stations.

Low elevation coastal zones (LECZ) are extensive throughout the southeastern United States. LECZ communities are threatened by inundation from sea level rise, storm surge, wetland degradation, land subsidence, and hydrological flooding. Communication among scientists, stakeholders, policy makers and minority and poor residents must improve. We must predict processes spanning the ecological, physical, social, and health sciences. Communities need to address linkages of (1) human and socioeconomic vulnerabilities; (2) public health and safety; (3) economic concerns; (4) land loss; (5) wetland threats; and (6) coastal inundation. Essential capabilities must include a network to assemble and distribute data and model code to assess risk and its causes, support adaptive management, and improve the resiliency of communities. Better communication of information and understanding among residents and officials is essential. Here we review recent background literature on these matters and offer recommendations for integrating natural and social sciences. We advocate for a cyber-network of scientists, modelers, engineers, educators, and stakeholders from academia, federal state and local agencies, non-governmental organizations, residents, and the private sector. Our vision is to enhance future resilience of LECZ communities by offering approaches to mitigate hazards to human health, safety and welfare and reduce impacts to coastal residents and industries.

A new method for the optimization of seasonal energy storage is presented and applied in a case study. The optimization method uses an interval halving approach to solve computationally demanding mixed integer linear programming (MILP) problems with both integer and non-integer operation variables (variables that vary from time step to time step in during energy storage system operation). The seasonal energy storage in the case study uses a reversible solid oxide cell (RSOC) to convert electricity generated by solar photovoltaic (PV) panels into hydrogen gas and to convert hydrogen gas back to electricity while also generating some heat. Both the case study results and the optimization method accuracy are examined and discussed in the paper. In the case study, the operation of the RSOC and hydrogen storage system is compared with the operation of a reference system without energy storage. The results of the study show that installing an RSOC and hydrogen storage system could increase the utilization of onsite renewable energy generation significantly. Overall, the optimization method presents a relatively accurate solution to the case study optimization problem and a sensibility analysis shows a clear and logical pattern.

Cone Beam Computed Tomography (CBCT) is a valuable imaging technique in oral and maxillofacial surgery (OMS) that can help direct a surgeon’s approach to a variety of conditions. A 3-dimensional analysis of head and neck anatomy allows practitioners to plan appropriately, operate with confidence, and assess results post-operatively. CBCT imaging has clear indications and limitations. CBCT offers the clinician 3-dimensional and multi-planar views for a more accurate diagnosis and treatment without the financial burden and radiation exposure of conventional computed tomography (CT) scans. Furthermore, CBCT overcomes certain limitations of 2-dimensional imaging, such as distortion, magnification, and superimposition. However, CBCT lacks the detailed depiction of soft tissue conditions for evaluation of pathologic conditions, head and neck infections, and temporomandibular joint (TMJ) disc evaluation. This review evaluates the evidence-based research supporting the application of CBCT in the various fields of oral and maxillofacial surgery, including dentoalveolar surgery, dental implants, TMJ, orthognathic surgery, trauma, and pathology, and will assess the value of CBCT in pre-operative assessment, surgical planning, and post-operative analysis when applicable. Additionally, the significant limitations of CBCT and potential areas for future research will be discussed.

BackgroundWe evaluated lipoprotein‐associated phospholipase A2 (Lp‐PLA2) activity in patients with stable coronary heart disease before and during treatment with darapladib, a selective Lp‐PLA2 inhibitor, in relation to outcomes and the effects of darapladib in the STABILITY trial. Methods and ResultsPlasma Lp‐PLA2 activity was determined at baseline (n=14 500); at 1 month (n=13 709); serially (n=100) at 3, 6, and 18 months; and at the end of treatment. Adjusted Cox regression models evaluated associations between Lp‐PLA2 activity levels and outcomes. At baseline, the median Lp‐PLA2 level was 172.4 μmol/min per liter (interquartile range 143.1–204.2 μmol/min per liter). Comparing the highest and lowest Lp‐PLA2 quartile groups, the hazard ratios were 1.50 (95% CI 1.23–1.82) for the primary composite end point (cardiovascular death, myocardial infarction, or stroke), 1.95 (95% CI 1.29–2.93) for hospitalization for heart failure, 1.42 (1.07–1.89) for cardiovascular death, and 1.37 (1.03–1.81) for myocardial infarction after adjustment for baseline characteristics, standard laboratory variables, and other prognostic biomarkers. Treatment with darapladib led to a ≈65% persistent reduction in median Lp‐PLA2 activity. There were no associations between on‐treatment Lp‐PLA2 activity or changes of Lp‐PLA2 activity and outcomes, and there were no significant interactions between baseline and on‐treatment Lp‐PLA2 activity or changes in Lp‐PLA2 activity levels and the effects of darapladib on outcomes. ConclusionsAlthough high Lp‐PLA2 activity was associated with increased risk of cardiovascular events, pharmacological lowering of Lp‐PLA2 activity by ≈65% did not significantly reduce cardiovascular events in patients with stable coronary heart disease, regardless of the baseline level or the magnitude of change of Lp‐PLA2 activity. Clinical Trial RegistrationURL: https://www.clinicaltrials.gov. Unique identifier: NCT00799903.

Evidence of the involvement of tryptophan and its metabolite, kynurenine, in various biological processes including cancer is constantly expanding. Analysis of cell extracts and culture media can allow for quick snapshots of the metabolic fluctuations occurring in vitro. Here, we describe a method for metabolite extraction from mammalian cells and analysis of extracted metabolites and cell culture media by HPLC with detection using an ultra-sensitive diode array detector.

Robert WeissAndroscoggin Cardiology Associates, Auburn, ME, USAAbstract: Nebivolol is a novel beta1-blocker with a greater degree of selectivity for beta1- adrenergic receptors than other agents in this class and a nitric oxide (NO)-potentiating, vasodilatory effect that is unique among beta-blockers currently available to clinicians (nebivolol is approved in Europe and is currently under review in the US). A NO-potentiating agent such as nebivolol may have an important role in hypertensive populations with reduced endothelial function such as diabetics, African-Americans and those with vascular disease. Nebivolol is a racemic mixture with beta-blocker activity residing in the d-isomer; in contrast, l-nebivolol is far more potent in facilitating NO release. Nebivolol is unique among betablockers in that, at doses