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Asymmetric propagation of acoustic waves is theoretically reported in a chirped phononic crystal made of the combination of two different nonlinear solids. The dispersion of the system is spatially dependent and allows the rainbow trapping inside the structure. Nonlinearity is used to activate the self-demodulation effect, which is enhanced due to the particular dispersion characteristics of the system. The performed numerical study reveals an efficient generation of the demodulated wave, up to 15% in terms of the pressure amplitude, as well as strong attenuation for undesired frequency components above the cut-off frequency. The obtained energy rectification ratio is in the order of 104 for the whole range of amplitudes employed in this work, indicating the robustness of the asymmetry and non-reciprocity of the proposed device for a wide operational range.

This work theoretically analyzes the sound absorption properties of a chirped multi-layer porous material including transmission, in particular showing the broadband unidirectional absorption properties of the system. Using the combination of the impedance matching condition and the balance between the leakage and the intrinsic losses, the system is designed to have broadband unidirectional and quasi perfect absorption. The transfer and scattering matrix formalism, together with numerical simulations based on the finite element method are used to demonstrate the results showing excellent agreement between them. The proposed system allows to construct broadband sound absorbers with improved absorption in the low frequency regime using less amount of material than the complete bulk porous layer.

The enhancement of sound inside a two dimensional exponentially chirped crystal during the soft reflections of waves is experimentally and theoretically explored in this work. The control of this enhancement is achieved by a gradual variation of the dispersion in the system by means of a chirp of the lattice constant. The sound enhancement is produced at some planes of the crystal in which the wave is softly reflected due to a progressive slowing down of the sound wave. We find that the character of the sound enhancement depends on the function of the variation of dispersion, i.e., on the function of the chirp. A simple coupled mode theory is proposed to find the analytical solutions of the sound wave enhancement in the exponentially chirped crystal. Harmonic and time domain numerical simulations are performed to interpret the concept of the soft reflections, and to check the analytically calculated field distributions both in good agreement with experiments. Specially we obtain stronger sound enhancement than in linearly chirped crystals. This sound enhancement could motivate applications in energy harvesting, e.g., to increase the efficiency of detectors and absorbers.

Understanding how allometric exponents vary in the different biologically determined patterns turns out to be fundamental for the development of a unifying hypothesis that intends to explain most of the variation among taxa and physiological states. The aims of this study were (i) to analyze the scaling exponents of oxygen consumption at different metabolic rates in Mytilus galloprovincialis according to different seasons, habitat, and acclimation to laboratory conditions and (ii) to examine the variation in shell morphology depending on habitat or seasonal environmental hazards. The allometric exponent for standard metabolic rate (b value) did not vary across seasons or tide level, presenting a consistent value of 0.644. However, the mass-specific standard oxygen consumption (a value), i.e. metabolic level, was lower in intertidal mussels (subtidal mussels: a = - 1.364; intertidal mussels: a = - 1.634). The allometric exponent for routine metabolic rate changed significantly with tide level: lower allometric exponents for intertidal mussels (b = 0.673) than for subtidal mussels (b = 0.871). This differential response did not change for at least two months after the environmental cue was removed. We suggest that this is the result of intertidal mussels investing fundamentally in surface-dependent organs (gill and shell), with the exception of the slightly higher values obtained in May as a likely consequence of gonadal tissue development. Subtidal mussels, on the contrary, are probably in constant demand for volume-related resources, which makes them consistently obtain an allometric exponent of around 0.87.

This large, multicenter, retrospective cohort study including onco-hematological neutropenic patients with Pseudomonas aeruginosa bloodstream infection (PABSI) found that among 1213 episodes, 411 (33%) presented with septic shock. The presence of solid tumors (33.3% vs. 20.2%, p < 0.001), a high-risk Multinational Association for Supportive Care in Cancer (MASCC) index score (92.6% vs. 57.4%; p < 0.001), pneumonia (38% vs. 19.2% p < 0.001), and infection due to multidrug-resistant P. aeruginosa (MDRPA) (33.8% vs. 21.1%, p < 0.001) were statistically significantly higher in patients with septic shock compared to those without. Patients with septic shock were more likely to receive inadequate empirical antibiotic therapy (IEAT) (21.7% vs. 16.2%, p = 0.020) and to present poorer outcomes, including a need for ICU admission (74% vs. 10.5%; p < 0.001), mechanical ventilation (49.1% vs. 5.6%; p < 0.001), and higher 7-day and 30-day case fatality rates (58.2% vs. 12%, p < 0.001, and 74% vs. 23.1%, p < 0.001, respectively). Risk factors for 30-day case fatality rate in patients with septic shock were orotracheal intubation, IEAT, infection due to MDRPA, and persistent PABSI. Therapy with granulocyte colony-stimulating factor and BSI from the urinary tract were associated with improved survival. Carbapenems were the most frequent IEAT in patients with septic shock, and the use of empirical combination therapy showed a tendency towards improved survival. Our findings emphasize the need for tailored management strategies in this high-risk population.

Background: We report the efficacy and safety of E‐52862—a selective, sigma‐1 receptor antagonist—from phase 2, randomized, proof‐of‐concept studies in patients with moderate‐to‐severe, neuropathic, chronic postsurgical pain (CPSP) and painful diabetic neuropathy (PDN). Methods: Adult patients (CPSP [N = 116]; PDN [N = 163]) were randomized at a 1:1 ratio to 4 weeks of treatment with E‐52862 (CPSP [n = 55]; PDN [n = 85]) or placebo (CPSP [n = 61]; PDN [n = 78]) orally once daily. Pain intensity scores were measured using a numerical pain rating scale from 0 (no pain) to 10 (worst pain imaginable). The primary analysis population comprised patients who received study drug with ≥1 baseline and on‐treatment observation (full analysis set). Results: In CPSP, mean baseline average pain was 6.2 for E‐52862 vs. 6.5 for placebo. Week 4 mean change from baseline (CFB) for average pain was −1.6 for E‐52862 vs. –0.9 for placebo (least squares mean difference [LSMD]: −0.9; p = 0.029). In PDN, mean baseline average pain was 5.3 for E‐52862 vs. 5.4 for placebo. Week 4 mean CFB for average pain was −2.2 for E‐52862 vs. –2.1 for placebo (LSMD: –0.1; p = 0.766). Treatment‐emergent adverse events (TEAEs) were reported in 90.9% of E‐52862‐treated patients vs. 76.7% of placebo‐treated patients in CPSP and 34.1% vs. 26.9% in PDN. Serious TEAEs occurred in CPSP only: E‐52862: 5.5%; placebo: 6.7%. Conclusions: E‐52862 demonstrated superior relief of CPSP vs. placebo after 4 weeks. Reductions in pain intensity were seen in PDN with E‐52862; high placebo response rates may have prevented differentiation between treatments. E‐52862 had acceptable tolerability in both populations. Significance Statement: These proof‐of‐concept studies validate the mode of action of E‐52862, a selective sigma‐1 receptor antagonist. In CPSP, E‐52862 resulted in clinically meaningful pain relief. In PDN, reductions in pain intensity were seen with E‐52862; high placebo response rates may have prevented differentiation between E‐52862 and placebo. These findings are clinically relevant given that neuropathic pain is highly incapacitating, lacking effective treatments and representing a significant unmet medical need, and support further development of sigma‐1 receptor antagonists for peripheral neuropathic pain. [ABSTRACT FROM AUTHOR]

BackgroundCDK4/6 inhibitors (CDKi), namely, palbociclib, ribociclib, and abemaciclib, combined with either an aromatase inhibitor (AI) or fulvestrant are the standard first/second line for hormone receptor-positive(HR+)/HER2-negative(neg) metastatic breast cancer (MBC). However, the choice of one specific CDKi is arbitrary and based on the physician’s experience with the drug, toxicity profile, and patient’s preferences, whereas biomarkers for optimal patient selection have not been established so far. Moreover, upfront chemotherapy is still recommended in case of clinical presentation with visceral crisis, despite no evidence of superior benefit for chemotherapy regimens against CDKi-based regimens. Recent correlative biomarker analyses from pivotal trials of palbociclib and ribociclib showed that HR+/HER2-neg MBC might respond differently according to the molecular intrinsic subtype, with Luminal A and B tumors being sensitive to both CDKi, Basal-like being insensitive to endocrine therapy, irrespective of CDKi, and HER2-enriched tumors showing a benefit only with ribociclib-based therapy.Clinical caseWe hereby present a paradigmatic clinical case of a woman affected by a relapsed HR+/HER2-neg MBC with bone and nodal lesions, presenting with a visceral crisis in the form of lymphangitis carcinomatosis and diagnosed with a molecularly HER2-enriched tumor, successfully treated with upfront ribociclib + fulvestrant. The patient experienced a complete symptomatic and radiologic remission of the lymphangitis with a partial response as best response, according to RECIST 1.1 criteria. The progression-free survival (PFS) was of 20 months, in line with the median PFS observed in the ribociclib + fulvestrant pivotal trial, where, however, patients with visceral crisis had been excluded.ConclusionsThis clinical case confirms in the real-world setting that non-luminal subtypes can be found in HR+/HER2-neg disease and may have potential therapeutic implications in the metastatic setting. It also questions the recommendation of upfront chemotherapy in the case of a visceral crisis in the era of CDKi-based regimens. These issues merit further evaluation in prospective and larger studies.

Simple Summary: This study raises the question whether all breast cancer patients need axillary lymph node dissection (ALND) after neoadjuvant chemotherapy (NAC). Researchers assessed a novel clinical variable: the sentinel lymph node ratio (SLN-R) to predict additional cancerous lymph nodes during ALND. SLN-R was defined as total number of positive sentinel nodes among all sentinel nodes removed during axillary staging after NAC. Axillary surgery included Targeted Axillary Dissection (TAD) technique for cN1 breast cancer patients. We analyzed data from 1521 patients, focusing on 118 with specific cancer stages and positive sentinel /TAD nodes results after NAC. The results indicated that an SLN-R value below 0.35 could suggest a lower chance of finding more cancerous nodes, with a 10.2% false-negative rate. This means SLN-R could help identify patients who might avoid unnecessary surgeries. By combining SLN-R with other clinical factors, the study aims to create a predictive tool, enhancing personalized care and improving patients' quality of life. Background/Objectives: The aim of the study was to determine the clinical value of the sentinel lymph node ratio (SLN-R) in predicting additional positive lymph nodes during axillary lymph node dissection (ALND) in breast cancer patients following neoadjuvant chemotherapy (NAC). Methods: A cross-sectional study was performed at a single institution evaluating data from 1521 BC patients. Inclusion criteria comprised cT1/cT4, cN0/cN1 status with positive post-NAC axillary staging by SLN/TAD, respectively, and subsequent ALND. Results: The study included 118 patients, divided into two groups based on the presence or absence of additional node metastasis at ALND: 39 in the residual disease group (RD) and 79 in the non-residual disease group (nRD). Univariate logistic regression analysis of SLN-R was conducted to assess its predictive value, yielding an odds ratio (OR) of 7.79 (CI 1.92–29.5, p = 0.003). An SLN-R cut-off point of <0.35 was identified using ROC curve analysis, with a false-negative rate of 10.2%, as a predictor for no additional metastasis at ALND following post-NAC SLN/TAD positivity. Conclusions: The study concludes that SLN-R is a valuable predictor for determining the omission of ALND in cases where SLN/TAD is positive after NAC. This metric, in combination with other clinical variables, could help develop a nomogram to spare patients from ALND. [ABSTRACT FROM AUTHOR]

Background: In the randomized, phase 3, SUSA‐301 trial, celecoxib‐tramadol co‐crystal (CTC) provided significantly greater analgesia compared with celecoxib, tramadol, or placebo in adults with acute, moderate‐to‐severe, postoperative pain. This post hoc, secondary analysis further evaluated the use of rescue medication and the incidence of treatment‐emergent adverse events (TEAEs). Methods: Patients (N = 637) were randomized 2:2:2:1 to receive oral CTC 200 mg twice daily (BID; n = 184), tramadol 50 mg four times daily (QID; n = 183), celecoxib 100 mg BID (n = 181), or placebo QID (n = 89). Post hoc analyses were conducted on the use of rescue medications up to 4 and 48 h post‐study drug dose, stratified by baseline pain intensity (moderate/severe), and on the incidence of TEAEs, stratified by rescue medication use. Results: A significantly lower proportion of patients received any rescue medication within 4 h post‐study dose with CTC (49.5%) versus tramadol (61.7%, p = 0.0178), celecoxib (65.2%, p = 0.0024), and placebo (75.3%, p = 0.0001); this was also seen for oxycodone use. Fewer patients in the CTC group received ≥3 doses of rescue medication compared with the other groups, irrespective of baseline pain intensity. In patients who did not receive opioid rescue medication, CTC was associated with a lower incidence of nausea and vomiting TEAEs versus tramadol alone. In patients who received rescue oxycodone, the incidence of nausea was similar in the CTC and tramadol groups, and higher versus celecoxib and placebo. Conclusion: Celecoxib‐tramadol co‐crystal was associated with reduced rescue medication use and an acceptable tolerability profile compared with tramadol or celecoxib alone in adults with acute, moderate‐to‐severe, postoperative pain. [ABSTRACT FROM AUTHOR]

Background: Breast cancer (BC) recurrence, defined as the reappearance of cancer in the ipsilateral breast after primary treatment, poses significant challenges in clinical management. Despite advances in treatment, recurrence rates persist, ranging from 0.6 to 1.5% annually, reaching 10–15% at 20 years. This study aims to analyze the surgical and oncological characteristics of patients with BC recurrence. Methods: This retrospective study includes 56 patients diagnosed with recurrent BC between October 2018 and April 2022. Data were collected from a prospectively maintained surgical database. A descriptive analysis was performed on the initial BC, and the recurrence, including surgical complications, was classified using the Clavien–Dindo system. The success rates of selective sentinel lymph node (SLN) biopsies and aberrant drainages were assessed based on previous surgeries. Results: The cohort included 55 females and 1 male, with a median age of 65.3 years. The mean time to BC recurrence was 11.5 years. Among them, 26.8% underwent breast-conserving surgery, 41.1% had a mastectomy, 21.4% had a mastectomy with reconstruction, and 10.7% had an excision over a previous mastectomy. An SLN biopsy was performed in 78.6% of cases, with higher success rates in those without a previous axillary lymph node dissection (85.7% vs. 63.2%). Aberrant drainage was more frequent in patients with a previous ALND (44.4% vs. 20%). The median follow-up was 41.3 months, with 10.7% experiencing a second recurrence. Conclusions: Repeat breast-conserving surgery with re-irradiation for ipsilateral recurrence is feasible and does not significantly increase complications. SLN biopsy is valuable for restaging and tailoring adjuvant therapies, with ALND not being necessary if re-SLN biopsy shows no drainage. The management of aberrant drainage remains controversial. [ABSTRACT FROM AUTHOR]

Abstract Background Identifying socioeconomic determinants that are associated with access to and availability of exercise facilities is fundamental to supporting physical activity engagement in urban populations, which in turn, may reduce health inequities. This study analysed the relationship between area-level socioeconomic status (SES) and access to, and availability of, exercise facilities in Madrid, Spain. Methods Area-level SES was measured using a composite index based on seven sociodemographic indicators. Exercise facilities were geocoded using Google Maps and classified into four types: public, private, low-cost and sessional. Accessibility was operationalized as the street network distance to the nearest exercise facility from each of the 125,427 residential building entrances (i.e. portals) in Madrid. Availability was defined as the count of exercise facilities in a 1000 m street network buffer around each portal. We used a multilevel linear regression and a zero inflated Poisson regression analyses to assess the association between area-level SES and exercise facility accessibility and availability. Results Lower SES areas had a lower average distance to the closest facility, especially for public and low-cost facilities. Higher SES areas had higher availability of exercise facilities, especially for private and seasonal facilities. Conclusion Public and low-cost exercise facilities were more proximate in low SES areas, but the overall number of facilities was lower in these areas compared with higher SES areas. Increasing the number of exercise facilities in lower SES areas may be an intervention to improve health equity.

Here, the authors experimentally report one-way transmission of ultrasonic waves by relying on the acoustic radiation pressure effect. This effect makes it possible to reconfigure a multilayer system by significantly deforming the water-air interface, achieving efficient nonreciprocal acoustic transmission.

Objectives: To assess the clinical features and outcomes of Pseudomonas aeruginosa bloodstream infection (PA BSI) in neutropenic patients with hematological malignancies (HM) and with solid tumors (ST), and identify the risk factors for 30-day mortality. Methods: We performed a large multicenter, retrospective cohort study including onco-hematological neutropenic patients with PA BSI conducted across 34 centers in 12 countries (January 2006–May 2018). Episodes occurring in hematologic patients were compared to those developing in patients with ST. Risk factors associated with 30-day mortality were investigated in both groups. Results: Of 1217 episodes of PA BSI, 917 occurred in patients with HM and 300 in patients with ST. Hematological patients had more commonly profound neutropenia (0.1 × 109 cells/mm) (67% vs. 44.6%; p < 0.001), and a high risk Multinational Association for Supportive Care in Cancer (MASCC) index score (32.2% vs. 26.7%; p = 0.05). Catheter-infection (10.7% vs. 4.7%; p = 0.001), mucositis (2.4% vs. 0.7%; p = 0.042), and perianal infection (3.6% vs. 0.3%; p = 0.001) predominated as BSI sources in the hematological patients, whereas pneumonia (22.9% vs. 33.7%; p < 0.001) and other abdominal sites (2.8% vs. 6.3%; p = 0.006) were more common in patients with ST. Hematological patients had more frequent BSI due to multidrug-resistant P. aeruginosa (MDRPA) (23.2% vs. 7.7%; p < 0.001), and were more likely to receive inadequate initial antibiotic therapy (IEAT) (20.1% vs. 12%; p < 0.001). Patients with ST presented more frequently with septic shock (45.8% vs. 30%; p < 0.001), and presented worse outcomes, with increased 7-day (38% vs. 24.2%; p < 0.001) and 30-day (49% vs. 37.3%; p < 0.001) case-fatality rates. Risk factors for 30-day mortality in hematologic patients were high risk MASCC index score, IEAT, pneumonia, infection due to MDRPA, and septic shock. Risk factors for 30-day mortality in patients with ST were high risk MASCC index score, IEAT, persistent BSI, and septic shock. Therapy with granulocyte colony-stimulating factor was associated with survival in both groups. Conclusions: The clinical features and outcomes of PA BSI in neutropenic cancer patients showed some differences depending on the underlying malignancy. Considering these differences and the risk factors for mortality may be useful to optimize their therapeutic management. Among the risk factors associated with overall mortality, IEAT and the administration of granulocyte colony-stimulating factor were the only modifiable variables.

Background: Breast cancer (BC) is the most prevalent cancer among females worldwide. Despite having survival rates beyond 90% in 5 years nowadays, BC has also the highest rates of lost disability-adjusted life years (DALYs) among all cancers. Sexual dysfunction (SD) is one of the most important causes of the problem, affecting between 40–80% of BC survivors. However, SD remains underdiagnosed and undertreated in the clinical practice. Therefore, this review is aimed to evaluate the assessment of SD in Breast Cancer Survivors (BCS) as well as specific causes affecting their sexual function and the potential therapeutic options for these patients. Methods: In December 2021, a search of observational studies evaluating the sexual function in BCS was performed through Ovid Medline, Embase, PubMed, Cochrane register of controlled trials (CCTR), Cochrane database of systematic reviews (CDSR), Cumulative Index to Nursing & Allied Health Literature (CINAHL) and Google scholar to identify potentially relevant publications. Articles that evaluated non-gynecological cancers were excluded, as well as those focusing on the sexuality of men. Results: Despite being such a prevalent entity and given the particularities of how BC affects the sexuality of patients, SD is not usually discussed in the clinical practice in BCS for various reasons, remaining therefore underdiagnosed and undertreated. SD in BC patients has a multifactorial aetiology, including among others, the effect of BC treatments (related to vaginal mucosae, fatigue, and joint pain), the psychological impact of the diagnostic itself and sociocultural influences related to the alteration of the breast. Various strategies have been suggested to treat SD in BC patients, including pharmacological, physical and psychological options. Evidence shows that vaginal moisturizers and psyco-educational therapies focusing on sexual health and couple-based ones improve sexual function; while systemic treatments and general psychological therapy have not demonstrated benefit. Regarding exercise programmes, body image perception has shown to be improved after a one-year strength training program. Conclusions: SD is a multifactorial condition that affects the quality of life of millions of BCS worldwide, severely underdiagnosed and undertreated up to date. A systematic assessment of sexual function in BCS could be useful to diagnose all cases prematurely to give adequate care and prevent its worsening. Specific treatment options for BCS are key potential investigation targets for the near future.