AZGP1 deficiency promotes angiogenesis in prostate cancer.

BACKGROUND: Loss of AZGP1 expression is a biomarker associated with progression to castration resistance, development of metastasis, and poor disease-specific survival in prostate cancer. However, high expression of AZGP1 cells in prostate cancer has been reported to increase proliferation and invasion. The exact role of AZGP1 in prostate cancer progression remains elusive. METHOD: AZGP1 knockout and overexpressing prostate cancer cells were generated using a lentiviral system. The effects of AZGP1 under- or over-expression in prostate cancer cells were evaluated by in vitro cell proliferation, migration, and invasion assays. Heterozygous AZGP1± mice were obtained from European Mouse Mutant Archive (EMMA), and prostate tissues from homozygous knockout male mice were collected at 2, 6 and 10 months for histological analysis. In vivo xenografts generated from AZGP1 under- or over-expressing prostate cancer cells were used to determine the role of AZGP1 in prostate cancer tumor growth, and subsequent proteomics analysis was conducted to elucidate the mechanisms of AZGP1 action in prostate cancer progression. AZGP1 expression and microvessel density were measured in human prostate cancer samples on a tissue microarray of 215 independent patient samples. RESULT: Neither the knockout nor overexpression of AZGP1 exhibited significant effects on prostate cancer cell proliferation, clonal growth, migration, or invasion in vitro. The prostates of AZGP1-/- mice initially appeared to have grossly normal morphology; however, we observed fibrosis in the periglandular stroma and higher blood vessel density in the mouse prostate by 6 months. In PC3 and DU145 mouse xenografts, over-expression of AZGP1 did not affect tumor growth. Instead, these tumors displayed decreased microvessel density compared to xenografts derived from PC3 and DU145 control cells, suggesting that AZGP1 functions to inhibit angiogenesis in prostate cancer. Proteomics profiling further indicated that, compared to control xenografts, AZGP1 overexpressing PC3 xenografts are enriched with angiogenesis pathway proteins, including YWHAZ, EPHA2, SERPINE1, and PDCD6, MMP9, GPX1, HSPB1, COL18A1, RNH1, and ANXA1. In vitro functional studies show that AZGP1 inhibits human umbilical vein endothelial cell proliferation, migration, tubular formation and branching. Additionally, tumor microarray analysis shows that AZGP1 expression is negatively correlated with blood vessel density in human prostate cancer tissues. CONCLUSION: AZGP1 is a negative regulator of angiogenesis, such that loss of AZGP1 promotes angiogenesis in prostate cancer. AZGP1 likely exerts heterotypical effects on cells in the tumor microenvironment, such as stromal and endothelial cells. This study sheds light on the anti-angiogenic characteristics of AZGP1 in the prostate and provides a rationale to target AZGP1 to inhibit prostate cancer progression.

Detección de nefrotóxicos y ajuste de dosis en pacientes con filtrado glomerular bajo realizado en farmacia comunitaria: metodología / Detection of nephrotoxicants and dose adjustment in patients with low glomerular filtration rate performed in community pharmacy: methodology

La enfermedad renal crónica es un problema prevalente y sin tratamiento específico. La detección tem prana es importante, siendo el Filtrado Glomerular estimado (FGe) una prueba muy asequible que puede realizarse en farmacia comunitaria. Si se presenta, es muy importante no dañar más el riñón evitando el uso de medicamentos nefrotóxicos y ajustar las dosis de otros medicamentos de eliminación renal, y la farmacia comunitaria está muy bien posicionada para ello. Objetivo: describir la metodología utilizada para detectar nefrotóxicos y ajustar dosis de otros medica mentos en farmacia comunitaria para su posterior derivación a atención primaria. Método: estudio experimental de seguimiento no controlado multicéntrico realizado en farmacias comunitarias de 4 comunidades autónomas de España. Se incluyen pacientes que cumplen criterios de inclusión y firman el consentimiento informado. Se estudian aquellos con FGe<60 ml/min/1,73m2 y se analiza su medicación utilizando el BOT Plus y otras 4 fuentes de información. Resultado: se incluyen 670 pacientes, 215 de ellos con FGe<60ml/min/1,73m2. De ellos 90 (41,9 %) necesitaron algún tipo de ajuste a juicio del farmacéutico. De estos 90 el 43,3 % (39) tuvieron algún tipo de cambio posteriormente a la intervención del farmacéutico. Conclusión: en pacientes con filtrado glomerular bajo, con la metodología adecuada, el farmacéutico comunitario es capaz de detectar la utilización de medicamentos nefrotóxicos o la utilización de medicamentos a dosis superiores a las recomendadas en función de su estado renal. Detección de nefrotóxicos y ajuste de dosis en pacientes con filtrado glomerular bajo realizado en farmacia comunitaria: metodología (AU)

Chronic kidney disease is a prevalent problem without specific treatment. Early detection is important and estimated glomerular filtration rate (eGFR) is a very affordable test that can be performed in community pharmacies. If present, it is very important not to further damage the kidney by avoiding the use of neph rotoxic drugs and adjusting the doses of other renal elimination drugs and the community pharmacy is very well positioned to do this. Objective: To describe the methodology used to detect nephrotoxic drugs and adjust doses of other drugs in community pharmacies for subsequent referral to primary care. Method: Multicentre experimental multicentre uncontrolled follow-up study carried out in communi ty pharmacies in 4 autonomous communities in Spain. Patients who met the inclusion criteria and signed the informed consent form were included. Those with eGFR <60 ml/min/1.73m2 were studied and their medication was analysed using the BOT Plus and 4 other sources of information. Result: 670 patients were included, 215 of them with eGFR<60ml/min/1.73m2. Of these 90 (41.9%) needed some type of adjustment in the pharmacist’s judgement. Of these 90, 43.3% (39) had some kind of change after the pharmacist’s intervention C onclusion: In patients with low glomerular filtration rate, with the appropriate methodology, the community pharmacist is able to detect the use of nephrotoxic drugs or the use of drugs at doses higher than those recommended according to their renal status (AU)

In sickness and in debt: The COVID-19 impact on sovereign credit risk.

The COVID-19 pandemic provides a unique setting in which to evaluate the importance of a country's fiscal capacity in explaining the relation between economic growth shocks and sovereign default risk. For a sample of 30 developed countries, we find a positive and significant sensitivity of sovereign default risk to the intensity of the virus's spread for fiscally constrained governments. Supporting the fiscal channel, we confirm the results for Eurozone countries and U.S. states, for which monetary policy can be held constant. Our analysis suggests that financial markets penalize sovereigns with low fiscal space, impairing their resilience to external shocks.

Synchronous primary cutaneous melanomas: a descriptive study of their clinical features, histology, genetic background of the patients and clinical outcomes.

BACKGROUND: Around 0.5% of cutaneous melanoma (CM) patients will present with synchronous melanomas when first seen. Moreover, 26-40% of patients with multiple primary melanomas present with synchronous lesions. OBJECTIVES: To assess the prevalence, clinical and histopathological characteristics, germline mutations and outcome in patients with synchronous melanoma. METHODS: Clinical and histopathological data from 4703 melanoma patients were included. Clinical, histological and genetic mutational status information was analysed. Kaplan-Meier curves were used to investigate survival outcomes. RESULTS: A total of 144 patients (3.06%) presented simultaneously with two or more primary melanomas. During follow-up, 25.7% of patients with synchronous melanoma developed a new primary melanoma compared to 8.6% of patients diagnosed with single melanoma (P < 0.001). Germinal CDKN2A mutations were identified in 10.7% of patients with synchronous melanomas and genetic variants in MC1R in 72%. No significant differences in all survival outcomes between patients with synchronous melanomas and single melanomas were found. CONCLUSION: Synchronous melanomas are more frequent than previously reported and are more frequent in older patients compared to single melanomas. Moreover, these patients have a higher risk of developing a new primary melanoma during follow-up and have higher rates of germline susceptibility variants. Nevertheless, these findings were not associated with worse outcomes.

Thermographic Evaluation of the Duration of Skin Cooling After Cryotherapy in Dogs Following Tibial Plateau Leveling Osteotomy Surgery.

Objective: To evaluate the duration of cooling after cryotherapy on the skin over stifle joints in dogs after tibial plateau leveling osteotomy (TPLO) surgery using thermography. Materials and Methods: Seventeen client-owned dogs of various breeds were enrolled in the study. Dogs underwent TPLO surgeries, and on the next day, thermal imaging was performed on the operated stifle prior to cryotherapy for baseline. Orthogonal views were repeated at 30-min intervals until the skin over the stifle had thermally equilibrated. An ice pack was applied for 20 min on the medial and lateral aspects of the stifle. Each stifle was then re-imaged every 15 min for the first 60 min then every 30 min subsequently until the temperature was within 1°C of the pre-cryotherapy temperature. Results: Mean skin temperature of the medial view showed no significance difference compared to baseline value at 45 min after cryotherapy was discontinued and after 60 min for the lateral and cranial views. Mean skin temperature was overall higher in the medial view compared to the lateral and cranial during the rewarming period (except immediately after cold application). Mean skin temperatures of all views combined showed a significant decrease in temperature during cryotherapy application, with a slow increase until a plateau was reached after 45 min of rewarming. Conclusions and Clinical Relevance: Dogs undergoing TPLO for cranial cruciate ligament injury showed quicker rewarming period of superficial tissues compared to previous studies. Cryotherapy is a beneficial modality to reduce superficial tissue temperature in dogs undergoing TPLO, acknowledging that these dogs may require more frequent cryotherapy post-operatively due to more rapid rewarming time compared to dogs without surgery.

Precision Metrology Meets Cosmology: Improved Constraints on Ultralight Dark Matter from Atom-Cavity Frequency Comparisons.

We conduct frequency comparisons between a state-of-the-art strontium optical lattice clock, a cryogenic crystalline silicon cavity, and a hydrogen maser to set new bounds on the coupling of ultralight dark matter to standard model particles and fields in the mass range of 10^{-16}-10^{-21} eV. The key advantage of this two-part ratio comparison is the differential sensitivity to time variation of both the fine-structure constant and the electron mass, achieving a substantially improved limit on the moduli of ultralight dark matter, particularly at higher masses than typical atomic spectroscopic results. Furthermore, we demonstrate an extension of the search range to even higher masses by use of dynamical decoupling techniques. These results highlight the importance of using the best-performing atomic clocks for fundamental physics applications, as all-optical timescales are increasingly integrated with, and will eventually supplant, existing microwave timescales.

Inherited MC1R variants in patients with melanoma are associated with better survival in women.

BACKGROUND: Women have a better melanoma prognosis, and fairer skin/hair colour. The presence of inherited MC1R variants has been associated with a better melanoma prognosis, but its interaction with sex is unknown. OBJECTIVES: To evaluate the relationship between germline MC1R status and survival, and determine any association with sex. METHODS: This was a cohort study including 1341 patients with melanoma from the Melanoma Unit of the Hospital Clinic of Barcelona, between January 1996 and April 2018. We examined known sex-related prognosis factors as they relate to features of melanoma and evaluated the sex-specific role of MC1R in overall and melanoma-specific survival. Hazard ratios (HRs) were calculated using univariate and multivariate Cox logistic regression. RESULTS: Men showed lower overall survival than women (P < 0·001) and the presence of inherited MC1R variants was not associated with better survival in our cohort. However, in women the presence of MC1R variants was associated with better overall survival in the multivariate analysis [HR 0·57, 95% confidence interval (CI) 0·38-0·85; P = 0·006] but not in men [HR 1·26, 95% CI 0·89-1·79; P = 0·185 (P-value for interaction 0·004)]. Analysis performed for melanoma-specific survival showed the same level of significance. CONCLUSIONS: Inherited MC1R variants are associated with improved overall survival in women with melanoma but not in men. Intrinsic sex-dependent features can modify the role of specific genes in melanoma prognosis. We believe that survival studies of patients with melanoma should include analysis by sex and MC1R genotype. What's already known about this topic? Inherited MC1R variants have been associated with a better melanoma prognosis, but their interaction with sex is unknown. What does this study add? MC1R variants are related to better overall survival and melanoma-specific survival in women but not in men. What is the translational message? These differences between the sexes could imply future changes in melanoma follow-up and treatment strategies. This provides a basis for understanding the interaction between sex-related genes and germline variants in cancer.

Detection of cell-free circulating BRAFV 600E by droplet digital polymerase chain reaction in patients with and without melanoma under dermatological surveillance.

BACKGROUND: The p.V600E mutation in the BRAF protein is the most frequent mutation in cutaneous melanoma and is a recurrent alteration found in common benign naevi. Analysis of the cell-free BRAF c.1799T>A, p.V600E mutation (cfBRAFV 600E ) in plasma has emerged as a biomarker for monitoring prognosis and treatment response in patients with melanoma. OBJECTIVES: To quantify cfBRAFV 600E levels in plasma from patients with melanoma and from patients without melanoma undergoing regular follow-up of their melanocytic lesions, in order to assess the clinical significance of the test. METHODS: We quantified cfBRAFV 600E by droplet digital polymerase chain reaction in plasma from 146 patients without melanoma undergoing continuous dermatological screening, from 26 stage III and seven stage IV patients with BRAF-mutant melanoma, and from 32 patients with melanoma who were free of disease for 3 or more years. RESULTS: Among disease-free patients and individuals without melanoma, 52% presented a high naevus count (> 50) and 49% had clinically atypical naevi. cfBRAFV 600E was detected in 71% of patients with stage IV melanoma and 15% with stage III, and in 1·4% of individuals without melanoma. No cfBRAFV 600E mutation was detected in disease-free patients with melanoma. Individuals without melanoma had lower cfBRAFV 600E levels than patients with melanoma. We established a variant allelic frequency of 0·26% or 5 copies mL-1 of cfBRAFV 600E as the optimal cutoff value for identifying patients with melanoma with > 99% specificity. CONCLUSIONS: This study suggests that naevus-related factors do not influence the detection of cfBRAFV 600E in individuals without melanoma, and supports the clinical diagnostic value of plasma cfBRAFV 600E quantification in patients with melanoma. What's already known about this topic? The analysis of the BRAF c.1799T>A (p.V600E) mutation in cell-free (cf)DNA has emerged as a potential biomarker for monitoring prognosis and treatment response in patients with metastatic BRAFV600E melanoma. The BRAFV600E alteration is a common genetic alteration found in benign proliferations such as melanocytic naevi. No information exists about the impact of the number of common acquired naevi or the presence of clinically atypical naevi in cfBRAFV600E detection in an individual. What does this study add? The cfBRAFV600E mutation is detected in plasma from a reduced number of individuals without melanoma undergoing continuous dermatological follow-up. A high number of naevi or the presence of clinically atypical naevi are factors that do not influence cfBRAFV600E detection in an individual. Both total cfBRAF concentration and cfBRAFV600E frequency are effective biomarkers in patients with advanced melanoma but not in patients at early stages or with micrometastases. What is the translational message? Detection of cfBRAFV600E in an individual is not influenced by naevus-related factors. cfBRAFV600E is a robust and reliable biomarker that can be used in dermatological surveillance programmes.

Engineering Quantum States of Matter for Atomic Clocks in Shallow Optical Lattices.

We investigate the effects of stimulated scattering of optical lattice photons on atomic coherence times in a state-of-the art ^{87}Sr optical lattice clock. Such scattering processes are found to limit the achievable coherence times to less than 12 s (corresponding to a quality factor of 1×10^{16}), significantly shorter than the predicted 145(40) s lifetime of ^{87}Sr's excited clock state. We suggest that shallow, state-independent optical lattices with increased lattice constants can give rise to sufficiently small lattice photon scattering and motional dephasing rates as to enable coherence times on the order of the clock transition's natural lifetime. Not only should this scheme be compatible with the relatively high atomic density associated with Fermi-degenerate gases in three-dimensional optical lattices, but we anticipate that certain properties of various quantum states of matter-such as the localization of atoms in a Mott insulator-can be used to suppress dephasing due to tunneling.

Análisis estructural cuantitativo del hueso alveolar trabecular de la mandíbula en tomografía computarizada multidetector: diferencias por tipo y estado dentario / Quantitative structural analysis of trabecular alveolar bone in the mandible by multidetector computed tomography: differences according to tooth presence and type

Antecedentes y objetivo: Existe una carencia de métricas cuantitativas de la calidad del hueso trabecular alveolar, factor determinante en implantología. El objetivo de este estudio es desarrollar una metodología con tomografía computarizada multidetector para objetivar la calidad del hueso trabecular y establecer diferencias entre los distintos tipos y el estado de las piezas dentarias mediante procesado de imágenes y análisis estructural. Materiales y métodos: Se analizan 20 pacientes con exploración de tomografía computarizada multidetector dental para la valoración del hueso mandibular y posiciones dentales. El análisis de las imágenes incluyó la segmentación automática de la mandíbula, obtención de secciones perpendiculares a la arcada dentaria y análisis estructural del hueso trabecular de cada sección. Se obtuvieron la ratio entre volumen de hueso y volumen total de la sección, el grosor, la separación y el número trabecular, y la atenuación promedio en unidades Hounsfield. Se analizaron diferencias entre tipos de diente (incisivos, caninos, premolares y molares) y entre estados de las piezas dentarias (ausente o presente). Resultados: Se obtuvieron diferencias estadísticamente significativas entre los tipos y estados de las piezas. Por tipo, los incisivos mostraron mayor ratio de hueso trabecular, con disminución progresiva para caninos, premolares y molares. Por estado, las secciones pertenecientes a dientes ausentes presentaron mayor ratio de hueso que con el diente presente. Conclusiones: La metodología desarrollada permite cuantificar las propiedades estructurales del hueso alveolar a partir de imágenes de tomografía computarizada multidetector. Los resultados obtenidos objetivan el estado del sustrato óseo de cara a la planificación y seguimiento de la colocación de implantes dentales

Background and objective: There is a lack of quantitative measures of the quality of alveolar trabecular bone, an important factor in implantology. This study aimed to develop a method of objectively assessing the quality of trabecular bone by means of image processing and structural analysis of multidetector computed tomography images and to establish differences between tooth types and tooth presence/absence. Materials and methods: We analyzed 20 patients who underwent multidetector computed tomography to evaluate mandibular bone and tooth positioning. Image analysis included automatic segmentation of the mandible, obtainment of sections perpendicular to the dental arch, and structural analysis of the trabecular bone in each section. We calculated the ratio between the volume of bone and the total volume of the section, the thickness, the trabecular number, and the mean attenuation in Hounsfield units. We analyzed the differences among different tooth types (incisors, canines, premolars, and molars) and between present and absent teeth. Results: We found statistically significant differences between different tooth types and between sections in which teeth were present or absent. Incisors had a greater ratio of trabecular bone; the ratio of trabecular bone progressively decreased from the incisors to the canines, premolars, and molars. The ratio of trabecular bone was greater in sections in which teeth were absent than in those in which teeth were present. Conclusions: The method allows to quantify the structural properties of alveolar bone from multidetector computed tomography images. Our results provide an objective picture of the bone substrate that can be useful for planning and following up dental implant procedures

Quantitative structural analysis of trabecular alveolar bone in the mandible by multidetector computed tomography: differences according to tooth presence and type. / Análisis estructural cuantitativo del hueso alveolar trabecular de la mandíbula en tomografía computarizada multidetector: diferencias por tipo y estado dentario.

BACKGROUND AND OBJECTIVE: There is a lack of quantitative measures of the quality of alveolar trabecular bone, an important factor in implantology. This study aimed to develop a method of objectively assessing the quality of trabecular bone by means of image processing and structural analysis of multidetector computed tomography images and to establish differences between tooth types and tooth presence/absence. MATERIALS AND METHODS: We analyzed 20 patients who underwent multidetector computed tomography to evaluate mandibular bone and tooth positioning. Image analysis included automatic segmentation of the mandible, obtainment of sections perpendicular to the dental arch, and structural analysis of the trabecular bone in each section. We calculated the ratio between the volume of bone and the total volume of the section, the thickness, the trabecular number, and the mean attenuation in Hounsfield units. We analyzed the differences among different tooth types (incisors, canines, premolars, and molars) and between present and absent teeth. RESULTS: We found statistically significant differences between different tooth types and between sections in which teeth were present or absent. Incisors had a greater ratio of trabecular bone; the ratio of trabecular bone progressively decreased from the incisors to the canines, premolars, and molars. The ratio of trabecular bone was greater in sections in which teeth were absent than in those in which teeth were present. CONCLUSIONS: The method allows to quantify the structural properties of alveolar bone from multidetector computed tomography images. Our results provide an objective picture of the bone substrate that can be useful for planning and following up dental implant procedures.

La violencia de pareja en las pacientes que consultan por dolor torácico en urgencias / Domestic violence against women patients seen with chest pain in the emergency department

OBJETIVOS: 1) Conocer la prevalencia de violencia de pareja (VP) en las pacientes que consultan a urgencias por dolor torácico. 2)Analizar la posible asociación entre VP y presencia/control de factores de riesgo vascular (FRV), manifestaciones psíquicas de estrés, demora en la solicitud de atención, manejo del episodio y pronóstico. MÉTODOS: Se incluyó a 125 mujeres. Se realizó entrevista dirigida, test del Partner Violence Screen (PVS), seguimiento telefónico a los 30 días y revisión del historial clínico al año. RESULTADOS: Veintisiete pacientes (21,6%) tenían historia de VP, que era vigente en 4 de ellas. Las mujeres que habían sufrido VP eran más jóvenes (53,7 ± 15,0 vs 64,0 ± 18,4; p = 0,020), presentaban más frecuentemente síndrome ansioso-depresivo (57,7% vs 13,5%; p < 0,001) y tardaron más en consultar (35,0 ± 65,2 días vs 7,9 ± 25,0días; p = 0,047). Entre las mujeres mayores (≥ 65 años) existía más dislipidemia (100% vs 60,4%; p = 0,039) y peor control de la presión arterial (buen control 20% vs 78,4%; p = 0,007) en las que tenían historia de VP. No hubo diferencias en los diagnósticos, pruebas, tiempo de estancia, ingresos o evolución entre las pacientes con historia de VP o sin ella, ni hubo diferencias según la vigencia de la VP. CONCLUSIONES: La existencia actual o previa de VP en las pacientes que consultan por dolor torácico en urgencias es elevada. La existencia de VP va asociada a un retraso en la consulta y a mayor ansiedad, y puede contribuir a un mal control de los FRV, pero no afecta la evolución a medio plazo

OBJECTIVES: 1) To determine the prevalence of intimate partner violence (IPV) in patients seen in the emergency department with chest pain. 2) To analyse the possible association between IPV and presence/control of vascular risk factors (VRF), psychic manifestations of stress, delay in requesting care, care received, and prognosis. METHODS: The study was conducted on 125 women, and included a targeted interview, the Partner Violence Screen (PVS) test, a 30-day follow-up telephone interview, and a one-year follow-up clinical history review. RESULTS: A total of 27 patients (21.6%) had a history of IPV, which was present in 4 of them. Women with a history of IPV were younger (53.7 ± 15.0 vs. 64.0 ± 18.4; P = .020), had more anxiety or a depressive syndrome (57.7% vs 13.5%; P < 0.001), and consulted later (35.0 ± 65.2days vs 7.9 ± 25.0days; P = .047). Among older women ( ≥ 65years), there was more dyslipidaemia (100% vs 60.4%; P = .039) and worse blood pressure control (good control 20% vs 78.4%; P = .007) in those with a history of IPV. There were no differences in the diagnoses, tests, length of stay, admissions or prognosis among patients with or without a history of IPV, and there were no differences according to chronology of IPV. CONCLUSIONS: The current or previous existence of IPV in patients who consult for chest pain in the emergency department is high. The existence of IPV is associated with a delay in consultation and greater anxiety, and may contribute to poor control of VRF, but does not affect the prognosis in the medium term

[Domestic violence against women patients seen with chest pain in the emergency department]. / La violencia de pareja en las pacientes que consultan por dolor torácico en urgencias.

OBJECTIVES: 1) To determine the prevalence of intimate partner violence (IPV) in patients seen in the emergency department with chest pain. 2)To analyse the possible association between IPV and presence/control of vascular risk factors (VRF), psychic manifestations of stress, delay in requesting care, care received, and prognosis. METHODS: The study was conducted on 125 women, and included a targeted interview, the Partner Violence Screen (PVS) test, a 30-day follow-up telephone interview, and a one-year follow-up clinical history review. RESULTS: A total of 27 patients (21.6%) had a history of IPV, which was present in 4 of them. Women with a history of IPV were younger (53.7±15.0 vs. 64.0±18.4; P=.020), had more anxiety or a depressive syndrome (57.7% vs 13.5%; P<0.001), and consulted later (35.0±65.2days vs 7.9±25.0days; P=.047). Among older women (≥65years), there was more dyslipidaemia (100% vs 60.4%; P=.039) and worse blood pressure control (good control 20% vs 78.4%; P=.007) in those with a history of IPV. There were no differences in the diagnoses, tests, length of stay, admissions or prognosis among patients with or without a history of IPV, and there were no differences according to chronology of IPV. CONCLUSIONS: The current or previous existence of IPV in patients who consult for chest pain in the emergency department is high. The existence of IPV is associated with a delay in consultation and greater anxiety, and may contribute to poor control of VRF, but does not affect the prognosis in the medium term.

Emergence of multi-body interactions in a fermionic lattice clock.

Alkaline-earth atoms have metastable 'clock' states with minute-long optical lifetimes, high-spin nuclei and SU(N)-symmetric interactions, making them powerful platforms for atomic clocks1, quantum information processing2 and quantum simulation3. Few-particle systems of such atoms provide opportunities to observe the emergence of complex many-body phenomena with increasing system size4. Multi-body interactions among particles are emergent phenomena, which cannot be broken down into sums over underlying pairwise interactions. They could potentially be used to create exotic states of quantum matter5,6, but have yet to be explored in ultracold fermions. Here we create arrays of isolated few-body systems in an optical clock based on a three-dimensional lattice of fermionic 87Sr atoms. We use high-resolution clock spectroscopy to directly observe the onset of elastic and inelastic multi-body interactions among atoms. We measure the frequency shifts of the clock transition for varying numbers of atoms per lattice site, from n = 1 to n = 5, and observe nonlinear interaction shifts characteristic of elastic multi-body effects. These measurements, combined with theory, elucidate an emergence of SU(N)-symmetric multi-body interactions, which are unique to fermionic alkaline-earth atoms. To study inelastic multi-body effects, we use these frequency shifts to isolate n-occupied sites in the lattice and measure the corresponding lifetimes of the clock states. This allows us to access the short-range few-body physics without experiencing the systematic effects that are encountered in a bulk gas. The lifetimes that we measure in the isolated few-body systems agree very well with numerical predictions based on a simple model for the interatomic potential, suggesting a universality in ultracold collisions. By connecting these few-body systems through tunnelling, the favourable energy and timescales of the interactions will allow our system to be used for studies of high-spin quantum magnetism7,8 and the Kondo effect3,9.

Effects of hyperbaric oxygen therapy on uncomplicated incisional and open wound healing in dogs.

OBJECTIVE: To determine the safety of a hyperbaric oxygen therapy (HBOT) protocol and its influence on the healing of uncomplicated open and incisional wounds in dogs. STUDY DESIGN: Prospective, controlled experimental study. ANIMALS: Adult dogs (n = 10). METHODS: Two 2 × 2-cm open wounds and two 3-cm-long full-thickness dermal incisions were created on the dorsum of each dog. Dogs in the hyperbaric oxygen treatment group (HBO) received HBOT once daily (1.7 atmospheres absolute [ATA], 30 minutes on day 1; 2.0 ATA, 40 minutes on days 2-7) for 7 consecutive days, and dogs in the control group (CON) received standardized wound care. Dogs were monitored during HBOT for adverse side effects. Total wound area, percentage epithelialization, and percentage contraction were compared for the open wounds. Subjective wound scores were compared for the open and incisional wounds. Biopsies of both wound types were taken and used to determine histopathology scores. Bacterial cultures were completed on open wounds. RESULTS: No difference was detected between HBO and CON uncomplicated open and incisional wounds at any time for contraction, epithelialization, subjective wound scores, histopathology scores, or bacterial loads. All HBO dogs tolerated hyperbaric oxygen treatments with no adverse effects. CONCLUSION: The HBOT protocol tested here was safe but did not enhance the healing of uncomplicated acute wounds and incisions of dogs. CLINICAL SIGNIFICANCE: These results do not provide evidence to support the use of HBOT to manage uncomplicated wounds in dogs.

Effects of low-level laser therapy on the healing of surgically closed incisions and surgically created open wounds in dogs.

OBJECTIVE: To determine the effects of low-level laser therapy (LLLT) on primarily closed incisions and full thickness open wounds in dogs. STUDY DESIGN: Prospective, masked, placebo-controlled design. ANIMAL POPULATION: Healthy intact female dogs (n = 10). METHODS: Dogs underwent bilateral flank ovariectomy procedures, and open wounds were created bilaterally with a punch biopsy. Each side of the dog (incision and open wound) was randomly assigned to the treatment (TX) group or the control (CN) group. The TX group received LLLT once daily for 5 days with a 980-nm laser and a total energy density of 5 J/cm2 . The CN group received a sham treatment (laser turned off) for an identical amount of time each day. The wounds were assessed visually; measured; photographed at postoperative days 3, 7, 11, and 14; and biopsied on postoperative days 7 and 14. A 2-way repeated measures multivariate analysis of variance was used to analyze differences between groups. RESULTS: There was no difference between groups for subjective assessment of healing time and wound measurements (P = .7). There was no difference in histopathologic assessment except that the CN group had more necrosis and perivascular lymphocytes and macrophages at day 7 (P = .03). The TX group had more perivascular lymphocytes and macrophages at day 14 (P = .01). CONCLUSION: LLLT did not appear to influence the healing of surgically created incisions and small wounds with the methodology reported here. CLINICAL SIGNIFICANCE: Results of this study do not support recommending LLLT to stimulate healing of uncomplicated, small wounds and incisions.

Imaging Optical Frequencies with 100 µHz Precision and 1.1 µm Resolution.

We implement imaging spectroscopy of the optical clock transition of lattice-trapped degenerate fermionic Sr in the Mott-insulating regime, combining micron spatial resolution with submillihertz spectral precision. We use these tools to demonstrate atomic coherence for up to 15 s on the clock transition and reach a record frequency precision of 2.5×10^{-19}. We perform the most rapid evaluation of trapping light shifts and record a 150 mHz linewidth, the narrowest Rabi line shape observed on a coherent optical transition. The important emerging capability of combining high-resolution imaging and spectroscopy will improve the clock precision, and provide a path towards measuring many-body interactions and testing fundamental physics.

A Fermi-degenerate three-dimensional optical lattice clock.

Strontium optical lattice clocks have the potential to simultaneously interrogate millions of atoms with a high spectroscopic quality factor of 4 × 1017 Previously, atomic interactions have forced a compromise between clock stability, which benefits from a large number of atoms, and accuracy, which suffers from density-dependent frequency shifts. Here we demonstrate a scalable solution that takes advantage of the high, correlated density of a degenerate Fermi gas in a three-dimensional (3D) optical lattice to guard against on-site interaction shifts. We show that contact interactions are resolved so that their contribution to clock shifts is orders of magnitude lower than in previous experiments. A synchronous clock comparison between two regions of the 3D lattice yields a measurement precision of 5 × 10-19 in 1 hour of averaging time.

KIT mutations and CD117 overexpression are markers of better progression-free survival in vulvar melanomas.

BACKGROUND: Few studies have addressed prognostic markers and none has correlated molecular status and prognosis in vulvar melanomas. OBJECTIVES: To evaluate the clinicopathological features of 95 cases of vulvar melanoma. METHODS: p53, CD117, Ki-67, neurofibromin, brafv600e and nrasq61r immunostains, and molecular analyses by either targeted next-generation or direct sequencing, were performed on available archival materials. RESULTS: Molecular testing detected mutations in KIT (44%), BRAF (25%), NF1 (22%), TP53 (17%), NRAS (9%) and TERT promoter (9%). Co-mutation of KIT and NF1 and of KIT and NRAS were identified in two and one cases, respectively. KIT mutations were significantly associated with better progression-free survival in univariate analyses. In multivariate analyses CD117 expression was significantly associated with better progression-free survival. Tumour thickness was significantly associated with worse progression-free and overall survival, and perineural invasion significantly correlated with reduced melanoma-specific survival and reduced overall survival. Cases were from multiple centres and only a subset of samples was available for molecular testing. CONCLUSIONS: KIT mutations and CD117 overexpression are markers of better progression-free survival. In addition to its prognostic value, molecular testing may identify cases that might respond to targeted agents or immunotherapeutic approaches.