An unmet need: Pancreatic beta cell replacement.

Diabetes mellitus (DM) is a growing public health concern in South Africa (SA) and poses a substantial economic burden on healthcare globally. A century has passed since the discovery of insulin, and despite advances in diabetes management, exogenous insulin remains a primary treatment for type 1 DM, posing challenges of hyperglycaemia and hypoglycaemia. Pancreas transplantation should be considered a treatment for insulin-deficient DM, offering sustained euglycaemia and preventing complications associated with the disease. However, there has been a global decrease in the number of transplants performed. In SA, only a few pancreas transplants have been performed, primarily because of surgical risks and the need for immunosuppression. Islet transplantation is an alternative but faces limitations due to donor scarcity and immunosuppression requirements. This review explores recent progress in pancreas and islet transplants for DM, with the aim of providing insights into expanding treatment options for people with insulin-deficient DM.

Demonstration of event position reconstruction based on diffusion in the NEXT-white detector.

Noble element time projection chambers are a leading technology for rare event detection in physics, such as for dark matter and neutrinoless double beta decay searches. Time projection chambers typically assign event position in the drift direction using the relative timing of prompt scintillation and delayed charge collection signals, allowing for reconstruction of an absolute position in the drift direction. In this paper, alternate methods for assigning event drift distance via quantification of electron diffusion in a pure high pressure xenon gas time projection chamber are explored. Data from the NEXT-White detector demonstrate the ability to achieve good position assignment accuracy for both high- and low-energy events. Using point-like energy deposits from 83mKr calibration electron captures (E∼45 keV), the position of origin of low-energy events is determined to 2 cm precision with bias <1mm. A convolutional neural network approach is then used to quantify diffusion for longer tracks (E≥1.5 MeV), from radiogenic electrons, yielding a precision of 3 cm on the event barycenter. The precision achieved with these methods indicates the feasibility energy calibrations of better than 1% FWHM at Qßß in pure xenon, as well as the potential for event fiducialization in large future detectors using an alternate method that does not rely on primary scintillation.

Ergodicity breaking from Rydberg clusters in a driven-dissipative many-body system.

It is challenging to probe ergodicity breaking trends of a quantum many-body system when dissipation inevitably damages quantum coherence originated from coherent coupling and dispersive two-body interactions. Rydberg atoms provide a test bed to detect emergent exotic many-body phases and nonergodic dynamics where the strong Rydberg atom interaction competes with and overtakes dissipative effects even at room temperature. Here, we report experimental evidence of a transition from ergodic toward ergodic breaking dynamics in driven-dissipative Rydberg atomic gases. The broken ergodicity is featured by the long-time phase oscillation, which is attributed to the formation of Rydberg excitation clusters in limit cycle phases. The broken symmetry in the limit cycle is a direct manifestation of many-body collective effects, which is verified experimentally by tuning atomic densities. The reported result reveals that Rydberg many-body systems are a promising candidate to probe ergodicity breaking dynamics, such as limit cycles, and enable the benchmark of nonequilibrium phase transition.

Utilization of cefepime therapeutic drug monitoring in febrile neutropenia patients with hematologic malignancies.

INTRODUCTION: Cefepime is a fourth-generation cephalosporin and is a workhorse for the empiric treatment of febrile neutropenia (FN). Beta-lactam therapeutic drug monitoring (TDM) has emerged as a dose optimization strategy in patient populations with altered kinetics. Prior literature has demonstrated that patients with FN exhibit augmented renal clearance which may lead to subtherapeutic drug concentrations with standard dosing regimens. The aim of this study was to evaluate pharmacokinetic/pharmacodynamic (PK/PD) target attainment and clinical outcomes in patients with hematologic malignancies and FN who were treated empirically with cefepime. METHODS: This was a prospective, single-center study of adults with hematologic malignancies and FN admitted to the inpatient unit. The primary outcome was PK/PD target attainment (defined as 100% free time greater than minimum inhibitory concentration (100% fT > MIC)). Secondary clinical outcomes were time to defervescence, time to ANC recovery, in-hospital mortality, and cefepime failure. RESULTS: There were 55 patients in our study. Forty-three (78%) patients achieved the primary outcome of PK/PD target attainment. The mean time to defervescence was similar between those that achieved PK/PD target attainment and those that did not (95% CI -0.75 to 1.25, p = 0.62). CONCLUSIONS: This study showed that standard cefepime dosing in patients with hematologic malignancies and FN does not result in achievement of 100% fT > MIC in all patients. Patients in the group that did not achieve PK/PD target attainment were younger with increased creatinine clearance, indicating that cefepime TDM may be especially beneficial in these patients.

Emergence of Synchronization in a Driven-Dissipative Hot Rydberg Vapor.

We observe synchronization in a thermal (35-60 °C) atomic (Rb) ensemble driven to a highly excited Rydberg state (principle quantum number n ranging from 43 to 79). Synchronization in this system is unexpected due to the atomic motion; however, we show theoretically that sufficiently strong interactions via a global Rydberg density mean field cause frequency and phase entrainment. The emergent oscillations in the vapor's bulk quantities are detected in the transmission of the probe laser for a two-photon excitation scheme.

Observation of Rydberg Blockade Due to the Charge-Dipole Interaction between an Atom and a Polar Molecule.

We demonstrate Rydberg blockade due to the charge-dipole interaction between a single Rb atom and a single RbCs molecule confined in optical tweezers. The molecule is formed by magnetoassociation of a Rb+Cs atom pair and subsequently transferred to the rovibrational ground state with an efficiency of 91(1)%. Species-specific tweezers are used to control the separation between the atom and molecule. The charge-dipole interaction causes blockade of the transition to the Rb(52s) Rydberg state, when the atom-molecule separation is set to 310(40) nm. The observed excitation dynamics are in good agreement with simulations using calculated interaction potentials. Our results open up the prospect of a hybrid platform where quantum information is transferred between individually trapped molecules using Rydberg atoms.

First Constraints on Heavy QCD Axions with a Liquid Argon Time Projection Chamber Using the ArgoNeuT Experiment.

We present the results of a search for heavy QCD axions performed by the ArgoNeuT experiment at Fermilab. We search for heavy axions produced in the NuMI neutrino beam target and absorber decaying into dimuon pairs, which can be identified using the unique capabilities of ArgoNeuT and the MINOS near detector. This decay channel is motivated by a broad class of heavy QCD axion models that address the strong CP and axion quality problems with axion masses above the dimuon threshold. We obtain new constraints at a 95% confidence level for heavy axions in the previously unexplored mass range of 0.2-0.9 GeV, for axion decay constants around tens of TeV.

Search for Subsolar-Mass Binaries in the First Half of Advanced LIGO's and Advanced Virgo's Third Observing Run.

We report on a search for compact binary coalescences where at least one binary component has a mass between 0.2 M_{⊙} and 1.0 M_{⊙} in Advanced LIGO and Advanced Virgo data collected between 1 April 2019 1500 UTC and 1 October 2019 1500 UTC. We extend our previous analyses in two main ways: we include data from the Virgo detector and we allow for more unequal mass systems, with mass ratio q≥0.1. We do not report any gravitational-wave candidates. The most significant trigger has a false alarm rate of 0.14 yr^{-1}. This implies an upper limit on the merger rate of subsolar binaries in the range [220-24200] Gpc^{-3} yr^{-1}, depending on the chirp mass of the binary. We use this upper limit to derive astrophysical constraints on two phenomenological models that could produce subsolar-mass compact objects. One is an isotropic distribution of equal-mass primordial black holes. Using this model, we find that the fraction of dark matter in primordial black holes in the mass range 0.2 M_{⊙}

[Phototherapeutic keratectomy for epithelial basement membrane dystrophy : Impact of excimer laser systems used on the changes of visual acuity, refraction and astigmatism]. / Phototherapeutische Keratektomie bei Epithel-Basalmembran-Dystrophie : Einfluss verwendeter Excimerlaser-Systeme auf die Entwicklung von Visus, Refraktion und Astigmatismus.

BACKGROUND: Excimer laser-assisted phototherapeutic keratectomy (PTK) has become established as the gold standard in treatment of epithelial basement membrane dystrophy (EBMD), commonly also known as map-dot-fingerprint dystrophy (MDF). At the Department of Ophthalmology, Saarland University Medical Center in Homburg/Saar, systems from Zeiss Meditec and Schwind have been used. The outcomes of both were compared in this study. PATIENTS AND METHODS: The retrospective study included patients who underwent PTK with a diagnosis of MDF between 2007 and 2017. A total of 170 operations were performed using Zeiss Meditec MEL-70 (Carl Zeiss Meditec AG, Jena, Germany) and 98 using a Schwind eye-tech-solutions Amaris 750S laser (Schwind eye-tech-solutions GmbH, Kleinostheim, Germany). Preoperative and postoperative data for visual acuity, refraction and astigmatism as well as curvature data from the Pentacam and endothelial cell count were collected. The follow-up period averaged 8 months. RESULTS: In both groups visual acuity postoperatively was significantly better (Zeiss: p < 0.001, Schwind p < 0.004). The improvement in the Schwind group was less than in the Zeiss group, which is the reason why there was a significant difference between the laser systems postoperatively (p < 0.017). There were no significant changes regarding the spherical equivalent after PTK. Regarding astigmatism, there was a significant decrease in the Zeiss group (p < 0.042), while it did not change significantly in patients treated with Schwind laser (p < 0.217). Overall, this led to a significant postoperative difference between both laser systems (p < 0.014). CONCLUSION: The PTK can be recommended as an effective treatment method for patients with EBMD, regardless of the laser systems used. Patients benefit from long relief from recurrences with improved or constant visual acuity and stable refraction.

Towards an in situ non-lethal rapid test to accurately detect the presence of the nematode parasite, Anguillicoloides crassus, in European eel, Anguilla anguilla.

Anguillicoloides crassus is an invasive nematode parasite of the critically endangered European eel, Anguilla anguilla, and possibly one of the primary drivers of eel population collapse, impacting many features of eel physiology and life history. Early detection of the parasite is vital to limit the spread of A. crassus, to assess its potential impact on spawning biomass. However accurate diagnosis of infection could only be achieved via necropsy. To support eel fisheries management we developed a rapid, non-lethal, minimally invasive and in situ DNA-based method to infer the presence of the parasite in the swim bladder. Screening of 131 wild eels was undertaken between 2017 and 2019 in Ireland and UK to validate the procedure. DNA extractions and PCR were conducted using both a Qiagen Stool kit and in situ using Whatman qualitative filter paper No1 and a miniPCR DNA Discovery-System™. Primers were specifically designed to target the cytochrome oxidase mtDNA gene region and in situ extraction and amplification takes approximately 3 h for up to 16 individuals. Our in-situ diagnostic procedure demonstrated positive predictive values at 96% and negative predictive values at 87% by comparison to necropsy data. Our method could be a valuable tool in the hands of fisheries managers to enable infection control and help protect this iconic but critically endangered species.

Evaluating the incidence of engraftment syndrome with different melphalan formulations in adult multiple myeloma and immunoglobulin light chain amyloidosis patients undergoing autologous hematopoietic cell transplantation.

BACKGROUND: Engraftment syndrome (ES) is a common complication of autologous hematopoietic cell transplantation (HCT). The difference in incidence of ES between melphalan formulations has not been widely reported throughout the literature and would allow for a more comprehensive understanding of the advantages and disadvantages of both melphalan formulations. PATIENTS AND METHODS: This retrospective, single-center, observational study evaluated 83 adult multiple myeloma and immunoglobulin light chain amyloidosis patients who received either propylene glycol-containing (PG) or propylene glycol-free (PG-free) melphalan 140 mg/m2 as single-agent conditioning chemotherapy for autologous HCT from May 31, 2015 to May 31, 2019. The primary outcome was to assess the incidence of ES, as defined using the Maiolino criteria, with both melphalan formulations. Secondary outcomes included an analysis of potential risk factors for the development of ES, as well as an evaluation of overall length of stay (LOS). RESULTS: The incidence of ES for PG and PG-free melphalan did not differ significantly, 14/39 (35.9%) and 12/44 (27.3%) (P = 0.4), respectively. No potential risk factors for ES were identified on multivariate logistic regression analysis. A statistically significant difference in number of days to engraftment was identified for PG and PG-free melphalan, 15.56 vs. 13.82 days (P = 0.01), respectively; although, this did not translate to a decrease in LOS, 19.9 vs. 18.59 days (P = 0.14). CONCLUSIONS: The incidence of ES did not differ significantly between melphalan formulations. Future research is needed to determine whether the faster time to engraftment seen with PG-free melphalan may translate to a decrease in LOS.

Rapid readout of terahertz orbital angular momentum beams using atom-based imaging.

We demonstrate the rapid readout of terahertz orbital angular momentum (OAM) beams using an atomic-vapor-based imaging technique. OAM modes with both azimuthal and radial indices are created using phase-only transmission plates. The beams undergo terahertz-to-optical conversion in an atomic vapor, before being imaged in the far field using an optical CCD camera. In addition to the spatial intensity profile, we also observe the self-interferogram of the beams by imaging through a tilted lens, allowing the sign and magnitude of the azimuthal index to be read out directly. Using this technique, we can reliably read out the OAM mode of low-intensity beams with high fidelity in 10 ms. Such a demonstration is expected to have far-reaching consequences for proposed applications of terahertz OAM beams in communications and microscopy.

Growth regulators and their reflection on different hop genotypes cultivated under in vitro conditions / Reguladores de crescimento e seu reflexo em diferentes genótipos de lúpulo cultivados in vitro

Hops is a new culture in Brazil. Tissue culture can be an important technique for rapid hop propagation. This paper aims to characterize responses from different genotypes under different growth regulators through the interrelationship of response variables important to hop in vitro growth. Three genotypes were cultivated in six culture media with different combinations of growth regulators, BAP (6-benzylaminopurine), IAA (3-indolacetic acid) and GA3 (gibberellic acid). The means were compared by orthogonal contrasts and the interrelationship of the response variables was performed by path analysis. American genotypes showed favorable root development under the BAP + IAA combination, while the use of IAA improved shoot development. The origin of genotypes was important for defining the best protocol for in vitro cultivation. The path coefficient showed that the variable number of shoots has stronger direct effect on the number of nodal segments. Additionally, in tissue culture assays, the use of a covariable and proper error distribution significantly increased experimental accuracy.

O lúpulo é uma nova cultura no Brasil. A cultura de tecidos pode ser uma técnica importante para a propagação rápida do lúpulo. Este artigo tem como objetivo caracterizar respostas de diferentes genótipos sob diferentes reguladores de crescimento através da inter-relação de variáveis de resposta importantes para o crescimento in vitro. Três genótipos foram cultivados em seis meios de cultura com diferentes combinações de reguladores de crescimento, BAP (6-benzilaminopurina), AIA (ácido 3-indolacético) e GA3 (ácido giberélico). As médias foram comparadas por contrastes ortogonais e a inter-relação das variáveis de resposta foi realizada por análise de trilha. Os genótipos americanos apresentaram desenvolvimento radicular favorável sob a combinação BAP + AIA, enquanto o uso do AIA melhorou o desenvolvimento da parte aérea. A origem dos genótipos foi importante para definir o melhor protocolo para o cultivo in vitro. O coeficiente de trilha mostrou que a variável número de brotos tem um efeito direto mais forte no número de segmentos nodais. Adicionalmente, em experimentos com cultura de tecidos, o uso de uma covariável e distribuição de erro adequada aumentou significativamente a precisão experimental.

Growth regulators and their reflection on different hop genotypes cultivated under in vitro conditions

Abstract Hops is a new culture in Brazil. Tissue culture can be an important technique for rapid hop propagation. This paper aims to characterize responses from different genotypes under different growth regulators through the interrelationship of response variables important to hop in vitro growth. Three genotypes were cultivated in six culture media with different combinations of growth regulators, BAP (6-benzylaminopurine), IAA (3-indolacetic acid) and GA3 (gibberellic acid). The means were compared by orthogonal contrasts and the interrelationship of the response variables was performed by path analysis. American genotypes showed favorable root development under the BAP + IAA combination, while the use of IAA improved shoot development. The origin of genotypes was important for defining the best protocol for in vitro cultivation. The path coefficient showed that the variable number of shoots has stronger direct effect on the number of nodal segments. Additionally, in tissue culture assays, the use of a covariable and proper error distribution significantly increased experimental accuracy.

Resumo O lúpulo é uma nova cultura no Brasil. A cultura de tecidos pode ser uma técnica importante para a propagação rápida do lúpulo. Este artigo tem como objetivo caracterizar respostas de diferentes genótipos sob diferentes reguladores de crescimento através da inter-relação de variáveis de resposta importantes para o crescimento in vitro. Três genótipos foram cultivados em seis meios de cultura com diferentes combinações de reguladores de crescimento, BAP (6-benzilaminopurina), AIA (ácido 3-indolacético) e GA3 (ácido giberélico). As médias foram comparadas por contrastes ortogonais e a inter-relação das variáveis de resposta foi realizada por análise de trilha. Os genótipos americanos apresentaram desenvolvimento radicular favorável sob a combinação BAP + AIA, enquanto o uso do AIA melhorou o desenvolvimento da parte aérea. A origem dos genótipos foi importante para definir o melhor protocolo para o cultivo in vitro. O coeficiente de trilha mostrou que a variável número de brotos tem um efeito direto mais forte no número de segmentos nodais. Adicionalmente, em experimentos com cultura de tecidos, o uso de uma covariável e distribuição de erro adequada aumentou significativamente a precisão experimental.

Growth regulators and their reflection on different hop genotypes cultivated under in vitro conditions / Reguladores de crescimento e seu reflexo em diferentes genótipos de lúpulo cultivados in vitro

Hops is a new culture in Brazil. Tissue culture can be an important technique for rapid hop propagation. This paper aims to characterize responses from different genotypes under different growth regulators through the interrelationship of response variables important to hop in vitro growth. Three genotypes were cultivated in six culture media with different combinations of growth regulators, BAP (6-benzylaminopurine), IAA (3-indolacetic acid) and GA3 (gibberellic acid). The means were compared by orthogonal contrasts and the interrelationship of the response variables was performed by path analysis. American genotypes showed favorable root development under the BAP + IAA combination, while the use of IAA improved shoot development. The origin of genotypes was important for defining the best protocol for in vitro cultivation. The path coefficient showed that the variable number of shoots has stronger direct effect on the number of nodal segments. Additionally, in tissue culture assays, the use of a covariable and proper error distribution significantly increased experimental accuracy.

O lúpulo é uma nova cultura no Brasil. A cultura de tecidos pode ser uma técnica importante para a propagação rápida do lúpulo. Este artigo tem como objetivo caracterizar respostas de diferentes genótipos sob diferentes reguladores de crescimento através da inter-relação de variáveis de resposta importantes para o crescimento in vitro. Três genótipos foram cultivados em seis meios de cultura com diferentes combinações de reguladores de crescimento, BAP (6-benzilaminopurina), AIA (ácido 3-indolacético) e GA3 (ácido giberélico). As médias foram comparadas por contrastes ortogonais e a inter-relação das variáveis de resposta foi realizada por análise de trilha. Os genótipos americanos apresentaram desenvolvimento radicular favorável sob a combinação BAP + AIA, enquanto o uso do AIA melhorou o desenvolvimento da parte aérea. A origem dos genótipos foi importante para definir o melhor protocolo para o cultivo in vitro. O coeficiente de trilha mostrou que a variável número de brotos tem um efeito direto mais forte no número de segmentos nodais. Adicionalmente, em experimentos com cultura de tecidos, o uso de uma covariável e distribuição de erro adequada aumentou significativamente a precisão experimental.

Point Absorber Limits to Future Gravitational-Wave Detectors.

High-quality optical resonant cavities require low optical loss, typically on the scale of parts per million. However, unintended micron-scale contaminants on the resonator mirrors that absorb the light circulating in the cavity can deform the surface thermoelastically and thus increase losses by scattering light out of the resonant mode. The point absorber effect is a limiting factor in some high-power cavity experiments, for example, the Advanced LIGO gravitational-wave detector. In this Letter, we present a general approach to the point absorber effect from first principles and simulate its contribution to the increased scattering. The achievable circulating power in current and future gravitational-wave detectors is calculated statistically given different point absorber configurations. Our formulation is further confirmed experimentally in comparison with the scattered power in the arm cavity of Advanced LIGO measured by in situ photodiodes. The understanding presented here provides an important tool in the global effort to design future gravitational-wave detectors that support high optical power and thus reduce quantum noise.

New Constraints on Tau-Coupled Heavy Neutral Leptons with Masses m_{N}=280-970 MeV.

A search for heavy neutral leptons has been performed with the ArgoNeuT detector exposed to the NuMI neutrino beam at Fermilab. We search for the decay signature N→νµ^{+}µ^{-}, considering decays occurring both inside ArgoNeuT and in the upstream cavern. In the data, corresponding to an exposure to 1.25×10^{20} POT, zero passing events are observed consistent with the expected background. This measurement leads to a new constraint at 90% confidence level on the mixing angle |U_{τN}|^{2} of tau-coupled Dirac heavy neutral leptons with masses m_{N}=280-970 MeV, assuming |U_{eN}|^{2}=|U_{µN}|^{2}=0.

Cosmic Ray Background Removal With Deep Neural Networks in SBND.

In liquid argon time projection chambers exposed to neutrino beams and running on or near surface levels, cosmic muons, and other cosmic particles are incident on the detectors while a single neutrino-induced event is being recorded. In practice, this means that data from surface liquid argon time projection chambers will be dominated by cosmic particles, both as a source of event triggers and as the majority of the particle count in true neutrino-triggered events. In this work, we demonstrate a novel application of deep learning techniques to remove these background particles by applying deep learning on full detector images from the SBND detector, the near detector in the Fermilab Short-Baseline Neutrino Program. We use this technique to identify, on a pixel-by-pixel level, whether recorded activity originated from cosmic particles or neutrino interactions.

Constraints on Cosmic Strings Using Data from the Third Advanced LIGO-Virgo Observing Run.

We search for gravitational-wave signals produced by cosmic strings in the Advanced LIGO and Virgo full O3 dataset. Search results are presented for gravitational waves produced by cosmic string loop features such as cusps, kinks, and, for the first time, kink-kink collisions. A template-based search for short-duration transient signals does not yield a detection. We also use the stochastic gravitational-wave background energy density upper limits derived from the O3 data to constrain the cosmic string tension Gµ as a function of the number of kinks, or the number of cusps, for two cosmic string loop distribution models. Additionally, we develop and test a third model that interpolates between these two models. Our results improve upon the previous LIGO-Virgo constraints on Gµ by 1 to 2 orders of magnitude depending on the model that is tested. In particular, for the one-loop distribution model, we set the most competitive constraints to date: Gµâ‰²4×10^{-15}. In the case of cosmic strings formed at the end of inflation in the context of grand unified theories, these results challenge simple inflationary models.

Growth regulators and their reflection on different hop genotypes cultivated under in vitro conditions.

Hops is a new culture in Brazil. Tissue culture can be an important technique for rapid hop propagation. This paper aims to characterize responses from different genotypes under different growth regulators through the interrelationship of response variables important to hop in vitro growth. Three genotypes were cultivated in six culture media with different combinations of growth regulators, BAP (6-benzylaminopurine), IAA (3-indolacetic acid) and GA3 (gibberellic acid). The means were compared by orthogonal contrasts and the interrelationship of the response variables was performed by path analysis. American genotypes showed favorable root development under the BAP + IAA combination, while the use of IAA improved shoot development. The origin of genotypes was important for defining the best protocol for in vitro cultivation. The path coefficient showed that the variable number of shoots has stronger direct effect on the number of nodal segments. Additionally, in tissue culture assays, the use of a covariable and proper error distribution significantly increased experimental accuracy.