Acceleration and focusing of relativistic electron beams in a compact plasma device.

Plasma wakefield acceleration represented a breakthrough in the field of particle accelerators by pushing beams to gigaelectronvolt energies within centimeter distances. The large electric fields excited by a driver pulse in the plasma can efficiently accelerate a trailing witness bunch paving the way toward the realization of laboratory-scale applications like free-electron lasers. However, while the accelerator size is tremendously reduced, upstream and downstream of it the beams are still handled with conventional magnetic optics with sizable footprints and rather long focal lengths. Here we show the operation of a compact device that integrates two active-plasma lenses with short focal lengths to assist the plasma accelerator stage. We demonstrate the focusing and energy gain of a witness bunch whose phase space is completely characterized in terms of energy and emittance. These results represent an important step toward the accelerator miniaturization and the development of next-generation table-top machines.

Guiding of Charged Particle Beams in Curved Plasma-Discharge Capillaries.

We present a new approach that demonstrates the deflection and guiding of relativistic electron beams over curved paths by means of the magnetic field generated in a plasma-discharge capillary. We experimentally prove that the guiding is much less affected by the beam chromatic dispersion with respect to a conventional bending magnet and, with the support of numerical simulations, we show that it can even be made dispersionless by employing larger discharge currents. This proof-of-principle experiment extends the use of plasma-based devices, that revolutionized the field of particle accelerators enabling the generation of GeV beams in few centimeters. Compared to state-of-the-art technology based on conventional bending magnets and quadrupole lenses, these results provide a compact and affordable solution for the development of next-generation tabletop facilities.

Synthesis and Characterization of Maghemite Nanoparticles Functionalized with Poly(Sodium 4-Styrene Sulfonate) Saloplastic and Its Acute Ecotoxicological Impact on the Cladoceran Daphnia magna.

Using a modified co-precipitation method, 11(2) nm γ-Fe2O3 nanoparticles functionalized with PSSNa [Poly(sodium 4-styrenesulfonate)] saloplastic polymer were successfully synthesized, and their structural, vibrational, electronic, thermal, colloidal, hyperfine, and magnetic properties were systematically studied using various analytic techniques. The results showed that the functionalized γ-Fe2O3/PSSNa nanohybrid has physicochemical properties that allow it to be applied in the magnetic remediation process of water. Before being applied as a nanoadsorbent in real water treatment, a short-term acute assay was developed and standardized using a Daphnia magna biomarker. The ecotoxicological tests indicated that the different concentrations of the functionalized nanohybrid may affect the mortality of the Daphnia magna population during the first 24 h of exposure. A lethal concentration of 533(5) mg L-1 was found. At high concentrations, morphological changes were also seen in the body, heart, and antenna. Therefore, these results suggested the presence of alterations in normal growth and swimming skills. The main changes observed in the D. magna features were basically caused by the PSSNa polymer due to its highly stable colloidal properties (zeta potential > -30 mV) that permit a direct and constant interaction with the Daphnia magna neonates.

Pyroclastic Dust from Arequipa-Peru Decorated with Iron Oxide Nanoparticles and Their Ecotoxicological Properties in Water Flea D. magna.

A novel magnetic composite made of Peruvian pyroclastic dust material decorated with maghemite nanoparticles was synthesized and characterized using a variety of analytic techniques. The 13 nm maghemite nanoparticles were grown on the pyroclastic dust using the conventional coprecipitation chemical route. A short-term acute assay was developed to study the ecotoxicological behavior of the water flea, Daphnia magna. A 24 h-lethal concentration (LC50) value equal to 123.6 mg L-1 was determined only for the magnetic composite. While the pyroclastic dust material did not exhibit a lethal concentration, it caused morphologically significant changes (p < 0.05) for heart and tail parameters at high concentrations. Morphologies exposed to the magnetic composite above the 24 h-LC50 revealed less tolerance and significant changes in the body, heart, antenna, and eye. Hence, it affects biomarker growth and swimming. The reproduction rate was not affected by the raw pyroclastic dust material. However, the number of individuals showed a decrease with increasing composite concentrations. The present study indicates the LC50 value, which can be used as a reference concentration for in-situ water cleaning with this material without damaging or changing the Daphnia magna ecosystem.

Ecotoxicological Properties of Pure and Phosphorus-Containing Graphene Oxide Bidimensional Sheets in Daphnia magna.

In this work, the synthesis and structural, thermal, vibrational, morphological, and electronic characterization of 2D-like pure graphene oxide (GO) and phosphorus-containing graphene oxide (GOP) sheets were investigated. The average thicknesses of GO and GOP were 0.8 µm and 3.1 µm, respectively. The electron energy-loss spectroscopy spectra were used to analyze the differences in the C-K and O-K energy edge bands between GO and GOP. In addition, colloidal stability was studied using dynamic light scattering and zeta potential physicochemical techniques, determining that as the concentration increases, the hydrodynamic diameter and electrostatic stability of GO and GOP increase. The colloidal stability was quite important to ensure the interaction between the suspended solid phase and the biomarker. The 2D-like materials were used to determine their ecotoxicological properties, such as the medium lethal concentration, a crucial parameter for understanding ecotoxicity. Acute ecotoxicity experiments (24 h) were conducted in triplicate to obtain robust statistics, with corresponding mean lethal concentration (LC50) of 11.4 mg L-1 and 9.8 mg L-1 for GO and GOP, respectively. The morphological parameters of GO and GOP were compared with a negative control. However, only the case of GO was analyzed, since the Daphnia magna (D. magna) set exposed to GOP died before completing the time required for morphological analysis. The results indicate that the GOP sample is more toxic than the GO, both during and after exposure. Furthermore, the morphological parameters with the greatest statistically significant changes (p<0.05) were associated with the heart and body, while the eye and tail showed less significant changes.

The pre-launch on-ground characterization of Ma_MISS spectrometer for ExoMars-Rosalind Franklin Rover mission. II. Radiometric calibration.

The Ma_MISS miniaturized spectrometer is integrated within the Drilling System of the ExoMars Rosalind Franklin Rover for Mars exploration. Here we focus on the on ground calibration campaign to obtain radiometric and linearity calibrations of the Ma_MISS instrument, while the first paper dealt with the spectral calibration [De Angelis et al., Rev. Sci. Instrum. 93, 123704 (2022)]. The experimental setup used to carry out radiometric calibration is described, as are the methods used for data processing and key parameter retrieval. In particular, the Spectrometer Transfer Function (Responsivity), Signal-to-Noise Ratio, and detector linearity are determined. In a third paper [De Sanctis et al., Planet. Sci. J. 3, 142 (2022)], validation of the Ma_MISS calibration results through spectral measurements performed on rock and synthetic targets during the radiometric calibration campaign is described.

Water activity in subaerial microbial biofilms on stone monuments.

Stone monuments can be difficult environments for life, particularly with respect to liquid water access. Nevertheless, microbial communities are found on them with apparent ubiquity. A variety of strategies for access to liquid water have been proposed. Regardless of their water-retention mechanisms details, though, we argue that water activity (a key indicator for cell viability) is constrained by environmental conditions, largely independently of community structure, and is predicted by the local temperature and relative humidity. However, direct measurement of water activity in SABs, particularly those growing on stone surfaces, is difficult. A method for estimating water activity within SABs is presented that uses a minimally invasive combination of conservative sampling, weather data, confocal imaging, and mathematical modeling. Applying the methodology to measurements from the marble roofs of the Federal Hall National Memorial and of the Thomas Jefferson Memorial, estimations are made for water activity in their subaerial stone communities over the course of an approximately one year period.

Genomic characterisation of hormone receptor-positive breast cancer arising in very young women.

BACKGROUND: Very young premenopausal women diagnosed with hormone receptor-positive, human epidermal growth factor receptor 2-negative (HR+HER2-) early breast cancer (EBC) have higher rates of recurrence and death for reasons that remain largely unexplained. PATIENTS AND METHODS: Genomic sequencing was applied to HR+HER2- tumours from patients enrolled in the Suppression of Ovarian Function Trial (SOFT) to determine genomic drivers that are enriched in young premenopausal women. Genomic alterations were characterised using next-generation sequencing from a subset of 1276 patients (deep targeted sequencing, n = 1258; whole-exome sequencing in a young-age, case-control subsample, n = 82). We defined copy number (CN) subgroups and assessed for features suggestive of homologous recombination deficiency (HRD). Genomic alteration frequencies were compared between young premenopausal women (<40 years) and older premenopausal women (≥40 years), and assessed for associations with distant recurrence-free interval (DRFI) and overall survival (OS). RESULTS: Younger women (<40 years, n = 359) compared with older women (≥40 years, n = 917) had significantly higher frequencies of mutations in GATA3 (19% versus 16%) and CN amplifications (CNAs) (47% versus 26%), but significantly lower frequencies of mutations in PIK3CA (32% versus 47%), CDH1 (3% versus 9%), and MAP3K1 (7% versus 12%). Additionally, they had significantly higher frequencies of features suggestive of HRD (27% versus 21%) and a higher proportion of PIK3CA mutations with concurrent CNAs (23% versus 11%). Genomic features suggestive of HRD, PIK3CA mutations with CNAs, and CNAs were associated with significantly worse DRFI and OS compared with those without these features. These poor prognostic features were enriched in younger patients: present in 72% of patients aged <35 years, 54% aged 35-39 years, and 40% aged ≥40 years. Poor prognostic features [n = 584 (46%)] versus none [n = 692 (54%)] had an 8-year DRFI of 84% versus 94% and OS of 88% versus 96%. Younger women (<40 years) had the poorest outcomes: 8-year DRFI 74% versus 85% and OS 80% versus 93%, respectively. CONCLUSION: These results provide insights into genomic alterations that are enriched in young women with HR+HER2- EBC, provide rationale for genomic subgrouping, and highlight priority molecular targets for future clinical trials.

A desiccated dual-species subaerial biofilm reprograms its metabolism and affects water dynamics in limestone.

Understanding the impact of sessile communities on underlying materials is of paramount importance in stone conservation. Up until now, the critical role of subaerial biofilms (SABs) whether they are protective or deteriorative remains unclear, especially under desiccation. The interest in desiccated SABs is raised by the prediction of an increase in drought events in the next decades that will affect the Mediterranean regions' rich stone heritage as never before. Thus, the main goal of this research is to study the effects of desiccation on both the biofilms' eco-physiology and its impacts on the lithic substrate. To this end, we used a dual-species model system composed of a phototroph and a chemotroph to simulate biofilm behavior on stone heritage. We found that drought altered the phototroph-chemotroph balance and enriched the biofilm matrix with proteins and DNA. Desiccated SABs underwent a shift in metabolism to fermentation and a decrease in oxidative stress. Additionally, desiccated SABs changed the water-related dynamics (adsorption, evaporation, and wetting properties) in limestone. Water absorption experiments showed that desiccated SABs protected the stone from rapid water uptake, while a thermographic survey indicated a delay in water evaporation. Spilling-drop tests revealed a change in the wettability of the stone-SAB interface, which affected the water transport properties of the stone. Finally, desiccated SABs reduced stone swelling in the presence of water vapor. The biodeteriorative and bioprotective implications of desiccated SABs on the stone were ultimately assessed.

ADHD and eating disorders in childhood and adolescence: An updated minireview.

INTRODUCTION: Attention-deficit/hyperactivity disorder (ADHD) is one of the most common neurodevelopmental disorders with overactivity, inattention, and impulsivity as core characteristics. Recent studies suggest that 20 % of children with ADHD also develop eating disorders (EDs), including anorexia nervosa, bulimia nervosa and binge eating disorder. However, little is still known about the association between ADHD and EDs through childhood and adolescence. Therefore, in the present work, we aimed at summarizing the studies investigating ADHD and EDs in childhood and adolescence over the last 10 years. METHODS: A bibliographic search on PubMed was performed and only studies that considered participants with a clinical diagnosis of ADHD, patients with an additional diagnosis of EDs and patients under 18 years old were included. A total of 7 studies were retrieved and included in the review. RESULTS: The majority of the reviewed studies (N = 5) found an association between ADHD and EDs, while the remaining, which focused on EDs symptomatology, reported either lower ED symptoms in ADHD sample or no association between ADHD and EDs. LIMITATIONS: the majority of studies were cross-sectional and therefore did not allow to explore the longitudinal casual relation between ADHD and EDs in the developmental age range considered. CONCLUSIONS: This review suggests that children and adolescents with ADHD should be monitored for EDs. However, more work is still needed to better understand the clinical implications of the comorbidity between ADHD and EDs and its prospective impact on the life of children and adolescents with ADHD.

Stable Operation of a Free-Electron Laser Driven by a Plasma Accelerator.

The breakthrough provided by plasma-based accelerators enabled unprecedented accelerating fields by boosting electron beams to gigaelectronvolt energies within a few centimeters [1-4]. This, in turn, allows the realization of ultracompact light sources based on free-electron lasers (FELs) [5], as demonstrated by two pioneering experiments that reported the observation of self-amplified spontaneous emission (SASE) driven by plasma-accelerated beams [6,7]. However, the lack of stability and reproducibility due to the intrinsic nature of the SASE process (whose amplification starts from the shot noise of the electron beam) may hinder their effective implementation for user purposes. Here, we report a proof-of-principle experiment using plasma-accelerated beams to generate stable and reproducible FEL light seeded by an external laser. FEL radiation is emitted in the infrared range, showing the typical exponential growth of its energy over six consecutive undulators. Compared to SASE, the seeded FEL pulses have energies 2 orders of magnitude larger and stability that is 3 times higher.

The pre-launch on-ground characterization of Mars Multispectral Imager for Subsurface Studies (Ma_MISS) spectrometer for ExoMars rover mission: Spectral calibration.

The Ma_MISS spectrometer is integrated within the drilling system of the Rosalind Franklin ExoMars rover. This paper reports the on-ground calibration campaign performed on the spectrometer. Here, we focus on the spectral calibration of the instrument. The experimental setup used to carry out calibration is described, and the methods used for data processing and key parameters retrieval are explained. In particular, the spectral parameters such as (i) pixel central wavelengths, (ii) spectral response function, (iii) spectral resolution, (iv) sampling, and (v) range are determined. In a follow-up paper, the linearity and radiometric calibrations are described, while in De Sanctis et al. [Planet. Sci. J. 3, 142 (2022)], the validation of spectral measurements performed on synthetic and natural rock targets is presented.

Sub-Lethal Concentrations of Graphene Oxide Trigger Acute-Phase Response and Impairment of Phase-I Xenobiotic Metabolism in Upcyte® Hepatocytes.

The impact of graphene oxide on hepatic functional cells represents a crucial evaluation step for its potential application in nanomedicine. Primary human hepatocytes are the gold standard for studying drug toxicity and metabolism; however, current technical limitations may slow down the large-scale diffusion of this cellular tool for in vitro investigations. To assess the potential hepatotoxicity of graphene oxide, we propose an alternative cell model, the second-generation upcyte® hepatocytes, which show metabolic and functional profiles akin to primary human hepatocytes. Cells were acutely exposed to sub-lethal concentrations of graphene oxide (≤80 µg/ml) for 24 h and stress-related cell responses (such as apoptosis, oxidative stress, and inflammatory response) were evaluated, along with a broad investigation of graphene oxide impact on specialized hepatic functions. Results show a mild activation of early apoptosis but not oxidative stress or inflammatory response in our cell model. Notably, while graphene oxide clearly impacted phase-I drug-metabolism enzymes (e.g., CYP3A4, CYP2C9) through the inhibition of gene expression and metabolic activity, conversely, no effect was observed for phase-II enzyme GST and phase-III efflux transporter ABCG2. The GO-induced impairment of CYP3A4 occurs concomitantly with the activation of an early acute-phase response, characterized by altered levels of gene expression and protein production of relevant acute-phase proteins (i.e., CRP, Albumin, TFR, TTR). These data suggest that graphene oxide induces an acute phase response, which is in line with recent in vivo findings. In conclusion, upcyte® hepatocytes appear a reliable in vitro model for assessing nanomaterial-induced hepatotoxicity, specifically showing that sub-lethal doses of graphene oxide have a negative impact on the specialized hepatic functions of these cells. The impairment of the cytochrome P450 system, along with the activation of an acute-phase response, may suggest potential detrimental consequences for human health, as altered detoxification from xenobiotics and drugs.

Free-electron lasing with compact beam-driven plasma wakefield accelerator.

The possibility to accelerate electron beams to ultra-relativistic velocities over short distances by using plasma-based technology holds the potential for a revolution in the field of particle accelerators1-4. The compact nature of plasma-based accelerators would allow the realization of table-top machines capable of driving a free-electron laser (FEL)5, a formidable tool to investigate matter at the sub-atomic level by generating coherent light pulses with sub-ångström wavelengths and sub-femtosecond durations6,7. So far, however, the high-energy electron beams required to operate FELs had to be obtained through the use of conventional large-size radio-frequency (RF) accelerators, bound to a sizeable footprint as a result of their limited accelerating fields. Here we report the experimental evidence of FEL lasing by a compact (3-cm) particle-beam-driven plasma accelerator. The accelerated beams are completely characterized in the six-dimensional phase space and have high quality, comparable with state-of-the-art accelerators8. This allowed the observation of narrow-band amplified radiation in the infrared range with typical exponential growth of its intensity over six consecutive undulators. This proof-of-principle experiment represents a fundamental milestone in the use of plasma-based accelerators, contributing to the development of next-generation compact facilities for user-oriented applications9.

Impacto de la variabilidad intrapaciente en la concentración sanguínea de anticalcineurínicos en los resultados del trasplante cardiaco / Impact of intrapatient blood level variability of calcineurin inhibitors on heart transplant outcomes

Introducción y objetivos: El objetivo es estudiar el impacto clínico de la variabilidad intrapaciente (VIP) de la concentración sanguínea de los anticalcineurínicos en el trasplante cardiaco, pues la información actual es escasa. Métodos: Se analizó retrospectivamente a pacientes de edad≥18 años con un trasplante cardiaco realizado entre 2000 y 2014 y con supervivencia≥1 año. La VIP se valoró mediante el coeficiente de variación de concentraciones entre los meses 4 a 12 postrasplante. El compuesto de rechazo, mortalidad o pérdida del injerto y la mortalidad o pérdida del injerto 1-5 años tras el trasplante se analizaron mediante regresión de Cox. Resultados: Se estudió a 1.581 receptores (edad, 56 años; mujeres, 21%), tratados con ciclosporina (790 pacientes) o tacrolimus (791 pacientes). En el análisis multivariable, un coeficiente de variación> 27,8% tendió a asociarse con el compuesto de rechazo/mortalidad (HR=1,298; IC95%, 0,993-1,695; p=0,056) y con la mortalidad (HR=1,387; IC95%, 0,979-1,963; p=0,065) a los 5 años. La asociación con el rechazo fue significativa al analizar a la población sin rechazos durante el primer año del trasplante (HR=1,609; IC95%, 1,129-2,295; p=0,011). El tacrolimus tuvo menos VIP que la ciclosporina, junto con unos mejores resultados por la menor influencia de la VIP. Conclusiones: La VIP de los anticalcineurínicos, especialmente con la inmunosupresión basada en el tacrolimus, se asocia solo marginalmente con los resultados a medio plazo del trasplante cardiaco, aunque puede tener influencia en los pacientes más estables durante el primer año tras el trasplante (AU)

Introduction and objectives: Intrapatient blood level variability (IPV) of calcineurin inhibitors has been associated with poor outcomes in solid-organ transplant, but data for heart transplant are scarce. Our purpose was to ascertain the clinical impact of IPV in a multi-institutional cohort of heart transplant recipients. Methods: We retrospectively studied patients aged ≥18 years, with a first heart transplant performed between 2000 and 2014 and surviving≥ 1 year. IPV was assessed by the coefficient of variation of trough levels from posttransplant months 4 to 12. A composite of rejection or mortality/graft loss or rejection and all-cause mortality/graft loss between years 1 to 5 posttransplant were analyzed by Cox regression analysis. Results: The study group consisted of 1581 recipients (median age, 56 years; women, 21%). Cyclosporine immediate-release tacrolimus and prolonged-release tacrolimus were used in 790, 527 and 264 patients, respectively. On multivariable analysis, coefficient of variation> 27.8% showed a nonsignificant trend to association with 5-year rejection-free survival (HR, 1.298; 95%CI, 0.993-1.695; P=.056) and with 5-year mortality (HR, 1.387; 95%CI, 0.979-1.963; P=.065). Association with rejection became significant on analysis of only those patients without rejection episodes during the first year posttransplant (HR, 1.609; 95%CI, 1.129-2.295; P=.011). The tacrolimus-based formulation had less IPV than cyclosporine and better results with less influence of IPV. Conclusions: IPV of calcineurin inhibitors is only marginally associated with mid-term outcomes after heart transplant, particularly with the tacrolimus-based immunosuppression, although it could play a role in the most stable recipients (AU)

Complicaciones infecciosas relacionadas con la asistencia circulatoria mecánica de corta duración en candidatos a trasplante cardiaco urgente / Infectious complications associated with short-term mechanical circulatory support in urgent heart transplant candidates

Introducción y objetivos: El uso de dispositivos de asistencia circulatoria mecánica de corta duración como puente a trasplante es frecuente en España. Se desconocen la epidemiología y la repercusión de las complicaciones infecciosas en estos pacientes. Métodos: Descripción sistemática de la epidemiología y análisis de la repercusión pronóstica de las complicaciones infecciosas en un registro multicéntrico retrospectivo de pacientes tratados con dispositivos de asistencia circulatoria mecánica de corta duración como puente a trasplante cardiaco urgente entre 2010 y 2015 en 16 hospitales españoles. Resultados: Se estudió a 249 pacientes; 87 (34,9%) de ellos tuvieron un total de 102 infecciones. La vía respiratoria fue la localización más frecuente (n=47; 46,1%). En 78 casos (76,5%) se obtuvo confirmación microbiológica; se aislaron en total 100 gérmenes causales, con predominio de bacterias gramnegativas (n=58, 58%). Los pacientes con complicaciones infecciosas presentaron mayor mortalidad durante el periodo de asistencia circulatoria mecánica (el 25,3 frente al 12,3%; p=0,009) y menor probabilidad de recibir un trasplante (el 73,6 frente al 85,2%; p=0,025) que los pacientes sin infección. La mortalidad posoperatoria tras el trasplante fue similar en ambos grupos (con infección, el 28,3%; sin infección, el 23,4%; p=0,471). Conclusiones: Los pacientes tratados con dispositivos de asistencia circulatoria mecánica de corta duración como puente al trasplante cardiaco están expuestos a un alto riesgo de complicaciones infecciosas, las cuales se asocian con una mayor mortalidad en espera del órgano (AU)

Introduction and objectives: Short-term mechanical circulatory support is frequently used as a bridge to heart transplant in Spain. The epidemiology and prognostic impact of infectious complications in these patients are unknown. Methods: Systematic description of the epidemiology of infectious complications and analysis of their prognostic impact in a multicenter, retrospective registry of patients treated with short-term mechanical devices as a bridge to urgent heart transplant from 2010 to 2015 in 16 Spanish hospitals. Results: We studied 249 patients, of which 87 (34.9%) had a total of 102 infections. The most frequent site was the respiratory tract (n=47; 46.1%). Microbiological confirmation was obtained in 78 (76.5%) episodes, with a total of 100 causative agents, showing a predominance of gram-negative bacteria (n=58, 58%). Compared with patients without infection, those with infectious complications showed higher mortality during the support period (25.3% vs 12.3%, P=.009) and a lower probability of receiving a transplant (73.6% vs 85.2%, P=.025). In-hospital posttransplant mortality was similar in the 2 groups (with infection: 28.3%; without infection: 23.4%; P=.471). Conclusions: Patients supported with temporary devices as a bridge to heart transplant are exposed to a high risk of infectious complications, which are associated with higher mortality during the organ waiting period (AU)

Time-resolved study of nonlinear photoemission in radio-frequency photoinjectors.

Photoemission is one of the fundamental processes that describes the generation of charged particles from materials irradiated by photons. The continuous progress in the development of ultrashort lasers allows investigation into the dynamics of the process at the femtosecond timescale. Here we report about experimental measurements using two ultrashort ultraviolet laser pulses to temporally probe the electrons release from a copper cathode in a radio-frequency photoinjector. By changing their relative delay, we studied how the release mechanism is affected by two-photon photoemission when tens of GW/cm2 intensities are employed. We evaluated the limits it poses on the achievable beam brightness and analyzed the resulting emission yield in terms of the electronic temperature by modeling the cathode as a two-temperature system.

Time-domain diffuse optics with 8.6 mm2 fast-gated SiPM for extreme light harvesting.

Fast time-gated single-photon detectors demonstrated high depth sensitivity in the detection of localized absorption perturbations inside scattering media, but their use for in vivo clinical applications-such as functional imaging of brain activation-was impaired by their small (<0.04mm2) active area. Here, we demonstrate, both on phantoms and in vivo, the performance of a fast-gated digital silicon photomultiplier (SiPM) that features an overall active area of 8.6mm2, overcoming the photon collection capability of established time-gated single-pixel detectors by orders of magnitude, enabling deep investigations within scattering media and high signal-to-noise ratios at late photon arrival times.

Phase II study of eribulin in combination with gemcitabine for the treatment of patients with locally advanced or metastatic triple negative breast cancer (ERIGE trial). Clinical and pharmacogenetic results on behalf of the Gruppo Oncologico Italiano di Ricerca Clinica (GOIRC).

BACKGROUND: The combination of a microtubule inhibitor (eribulin) with a nucleoside analog (gemcitabine) may synergistically induce tumor cell death, particularly in triple negative breast cancer (TNBC) characterized by high cell proliferation, aggressive behavior, and chemo-resistance. PATIENTS AND METHODS: This is an open-label, multicenter phase II study evaluating the combination of eribulin (0.88 mg/m2) plus gemcitabine (1000 mg/m2) on days 1 and 8 of a 21-day cycle as either first- or second-line treatment of locally advanced or metastatic TNBC. The primary endpoint was the objective response for evaluable patients. A prospective, molecular correlative study was carried out to assess the role of germinal BRCA pathogenic variants and single nucleotide polymorphisms (SNPs) in predicting efficacy and toxicity of the combination regimen. RESULTS: From July 2013 to September 2016, 83 evaluable patients were enrolled. They received a median number of six cycles of treatment. An overall response rate (ORR) of 37.3% (31 patients) was observed, with a complete response rate of 2.4% and a partial response rate of 34.9%; the clinical benefit rate was 48.8%. With a median follow-up of 28.8 months, the median response duration was 6.6 months, the median progression-free survival (PFS) was 5.1 months, and the median overall survival (OS) was 14.5 months. The most common grade 3-4 adverse events were aminotransferase elevation (in 25% of the patients) and neutropenia (in 23.8%). Women with BRCA1/2 pathogenic variants were associated with worse ORR, PFS, and OS than BRCA1/2 wild-type carriers. CYP3A4 and FGD4 SNPs were associated with increased risk of liver toxicity. Three different SNPs in CDA∗2, RRM1, and CYP2C8 genes were significantly associated with poorer OS. CONCLUSIONS: The combination of eribulin and gemcitabine showed promising activity and a moderate toxicity profile in metastatic TNBC. BRCA status and pharmacogenetics tests may help identify patients with high probability of response with negligible toxicity. EUDRACT NUMBER: 2012-003505-10.

The management of emergency spinal surgery during the COVID-19 pandemic in Italy.

AIMS: The current pandemic caused by COVID-19 is the biggest challenge for national health systems for a century. While most medical resources are allocated to treat COVID-19 patients, several non-COVID-19 medical emergencies still need to be treated, including vertebral fractures and spinal cord compression. The aim of this paper is to report the early experience and an organizational protocol for emergency spinal surgery currently being used in a large metropolitan area by an integrated team of orthopaedic surgeons and neurosurgeons. METHODS: An organizational model is presented based on case centralization in hub hospitals and early management of surgical cases to reduce hospital stay. Data from all the patients admitted for emergency spinal surgery from the beginning of the outbreak were prospectively collected and compared to data from patients admitted for the same reason in the same time span in the previous year, and treated by the same integrated team. RESULTS: A total of 19 patients (11 males and eight females, with a mean age of 49.9 years (14 to 83)) were admitted either for vertebral fracture or spinal cord compression in a 19-day period, compared to the ten admitted in the previous year. No COVID-19 patients were treated. The mean time between admission and surgery was 1.7 days, significantly lower than 6.8 days the previous year (p < 0.001). CONCLUSION: The structural organization and the management protocol we describe allowed us to reduce the time to surgery and ultimately hospital stay, thereby maximizing the already stretched medical resources available. We hope that our early experience can be of value to the medical communities that will soon be in the same emergency situation. Cite this article: Bone Joint J 2020;102-B(6):671-676.