A practical approach to screening for carbapenemase-producing Enterobacterales- views of a group of multidisciplinary experts from English hospitals.

INTRODUCTION: Carbapenemase-producing Enterobacterales (CPE) are an important public health threat, with costly operational and economic consequences for NHS Integrated Care Systems and NHS Trusts. UK Health Security Agency guidelines recommend that Trusts use locally developed risk assessments to accurately identify high-risk individuals for screening, and implement the most appropriate method of testing, but this presents many challenges. METHODS: A convenience sample of cross-specialty experts from across England met to discuss the barriers and practical solutions to implementing UK Health Security Agency framework into operational and clinical workflows. The group derived responses to six key questions that are frequently asked about screening for CPE. KEY FINDINGS: Four patient groups were identified for CPE screening: high-risk unplanned admissions, high-risk elective admissions, patients in high-risk units, and known positive contacts. Rapid molecular testing is a preferred screening method for some of these settings, offering faster turnaround times and more accurate results than culture-based testing. It is important to stimulate action now, as several lessons can be learnt from screening during the COVID-19 pandemic, as well as from CPE outbreaks. CONCLUSION: Further decisive and instructive information is needed to establish CPE screening protocols based on local epidemiology and risk factors. Local management should continually evaluate local epidemiology, analysing data and undertaking frequent prevalence studies to understand risks, and prepare resources- such as upscaled screening- to prevent increasing prevalence, clusters or outbreaks. Rapid molecular-based methods will be a crucial part of these considerations, as they can reduce unnecessary isolation and opportunity costs.

Extending the Hoyle-State Paradigm to

Carbon burning is a key step in the evolution of massive stars, Type 1a supernovae and superbursts in x-ray binary systems. Determining the ^{12}C+^{12}C fusion cross section at relevant energies by extrapolation of direct measurements is challenging due to resonances at and below the Coulomb barrier. A study of the ^{24}Mg(α,α^{'})^{24}Mg reaction has identified several 0^{+} states in ^{24}Mg, close to the ^{12}C+^{12}C threshold, which predominantly decay to ^{20}Ne(ground state)+α. These states were not observed in ^{20}Ne(α,α_{0})^{20}Ne resonance scattering suggesting that they may have a dominant ^{12}C+^{12}C cluster structure. Given the very low angular momentum associated with sub-barrier fusion, these states may play a decisive role in ^{12}C+^{12}C fusion in analogy to the Hoyle state in helium burning. We present estimates of updated ^{12}C+^{12}C fusion reaction rates.

Solving the Puzzles of the Decay of the Heaviest Known Proton-Emitting Nucleus

Two long-standing puzzles in the decay of ^{185}Bi, the heaviest known proton-emitting nucleus are revisited. These are the nonobservation of the 9/2^{-} state, which is the ground state of all heavier odd-A Bi isotopes, and the hindered nature of proton and α decays of its presumed 60-µs 1/2^{+} ground state. The ^{185}Bi nucleus has now been studied with the ^{95}Mo(^{93}Nb,3n) reaction in complementary experiments using the Fragment Mass Analyzer and Argonne Gas-Filled Analyzer at Argonne National Laboratory's ATLAS facility. The experiments have established the existence of two states in ^{185}Bi; the short-lived T_{1/2}=2.8_{-1.0}^{+2.3} µs, proton- and α-decaying ground state, and a 58(2)-µs γ-decaying isomer, the half-life of which was previously attributed to the ground state. The reassignment of the ground-state lifetime results in a proton-decay spectroscopic factor close to unity and represents the only known example of a ground-state proton decay to a daughter nucleus (^{184}Pb) with a major shell closure. The data also demonstrate that the ordering of low- and high-spin states in ^{185}Bi is reversed relative to the heavier odd-A Bi isotopes, with the intruder-based 1/2^{+} configuration becoming the ground, similar to the lightest At nuclides.

Shape Changes in the Mirror Nuclei

We studied the proton-rich T_{z}=-1 nucleus ^{70}Kr through inelastic scattering at intermediate energies in order to extract the reduced transition probability, B(E2;0^{+}→2^{+}). Comparison with the other members of the A=70 isospin triplet, ^{70}Br and ^{70}Se, studied in the same experiment, shows a 3σ deviation from the expected linearity of the electromagnetic matrix elements as a function of T_{z}. At present, no established nuclear structure theory can describe this observed deviation quantitatively. This is the first violation of isospin symmetry at this level observed in the transition matrix elements. A heuristic approach may explain the anomaly by a shape change between the mirror nuclei ^{70}Kr and ^{70}Se contrary to the model predictions.

Graphene oxide biopolymer aerogels for the removal of lead from drinking water using a novel nano-enhanced ion exchange cascade.

Potable water in developing countries often contains levels of toxic metals that exceed the recommended international limits, with impacts on human health. The aim of the present study was to develop a low cost aerogel synthesised from graphene oxide (GO) cross-linked with alginate to remove Pb2+ from potable water. Aerogels were made by a sol-gel of the composite materials followed by a freeze drying method. The shape of the aerogels were 50 mm diameter disks, 5 mm deep and characterised by an open porous network of 50 to 150 micrometres which are mechanically robust upon hydration. Firstly, the study was conducted using a batch adsorption method from a starting concentration 0.48 mM (100 mg/l) of Pb2+ in ultrapure water over 240 min, n = 4 with controls. A second series of experiments compared the adsorption of different competing ions at different valencies (Na+, Ca2+, Cu2+, La3+) in an equivalent media. A third series of experiments explored Pb2+ desorption from the aerogel at low pH and in highly acidic conditions. This simple filter system, based on a batch adsorption methodology expresses a high affinity for Pb2+ resulting in an ultra-high mean maximum adsorption capacity of 504 mg/g of Pb2+ within 240 mins at pH 5. The aerogel can also adsorb other toxic metal salts such as La3+ and Cu2+ with a capacity of 146 and 193 mg/g respectively. Furthermore, the aerogel structure can be acid washed removing 98% of the Pb2+ from the structure within three minutes. Overall, the data shows that GO alginate aerogels are highly effective at removing Pb2+ from water and the primary mechanism involved is ion exchange, although other phenomenon such as proton tunnelling may be a contributing factor to the ultra-high efficiency of the aerogel for Pb2+ remediation.

Establishing the Maximum Collectivity in Highly Deformed N=Z Nuclei.

The lifetimes of the first excited 2^{+} states in the N=Z nuclei ^{80}Zr, ^{78}Y, and ^{76}Sr have been measured using the γ-ray line shape method following population via nucleon-knockout reactions from intermediate-energy rare-isotope beams. The extracted reduced electromagnetic transition strengths yield new information on where the collectivity is maximized and provide evidence for a significant, and as yet unexplained, odd-odd vs even-even staggering in the observed values. The experimental results are analyzed in the context of state-of-the-art nuclear density-functional model calculations.

Advances in the Direct Study of Carbon Burning in Massive Stars.

The ^{12}C+^{12}C fusion reaction plays a critical role in the evolution of massive stars and also strongly impacts various explosive astrophysical scenarios. The presence of resonances in this reaction at energies around and below the Coulomb barrier makes it impossible to carry out a simple extrapolation down to the Gamow window-the energy regime relevant to carbon burning in massive stars. The ^{12}C+^{12}C system forms a unique laboratory for challenging the contemporary picture of deep sub-barrier fusion (possible sub-barrier hindrance) and its interplay with nuclear structure (sub-barrier resonances). Here, we show that direct measurements of the ^{12}C+^{12}C fusion cross section may be made into the Gamow window using an advanced particle-gamma coincidence technique. The sensitivity of this technique effectively removes ambiguities in existing measurements made with gamma ray or charged-particle detection alone. The present cross-section data span over 8 orders of magnitude and support the fusion-hindrance model at deep sub-barrier energies.

Grading immunohistochemical markers p16INK4a and HPV E4 identifies productive and transforming lesions caused by low- and high-risk HPV within high-grade anal squamous intraepithelial lesions.

OBJECTIVES: Because current guidelines recognise high-grade anal squamous intraepithelial lesions (HSILs) and low-grade SILs (LSILs), and recommend treatment of all HSILs although not all progress to cancer, this study aims to distinguish transforming and productive HSILs by grading immunohistochemical (IHC) biomarkers p16INK 4a (p16) and E4 in low-risk human papillomavirus (lrHPV) and high-risk (hr)HPV-associated SILs as a potential basis for more selective treatment. METHODS: Immunostaining for p16 and HPV E4 was performed and graded in 183 biopsies from 108 HIV-positive men who have sex with men. The causative HPV genotype of the worst lesion was identified using the HPV SPF10-PCR-DEIA-LiPA25 version 1 system, with laser capture microdissection for multiple infections. The worst lesions were scored for p16 (0-4) to identify activity of the hrHPV E7 gene, and panHPV E4 (0-2) to mark HPV production and life cycle completion. RESULTS: There were 37 normal biopsies, 60 LSILs and 86 HSILs, with 85% of LSILs caused by lrHPV and 93% of HSILs by hrHPV. No normal biopsy showed E4, but 43% of LSILs and 37% of HSILs were E4 positive. No differences in E4 positivity rates were found between lrHPV and hrHPV lesions. Most of the lesions caused by lrHPV (90%) showed very extensive patchy p16 staining; p16 grade in HSILs was variable, with frequency of productive HPV infection dropping with increasing p16 grade. CONCLUSIONS: Combined p16/E4 IHC identifies productive and nonproductive HSILs associated with hrHPV within the group of HSILs defined by the Lower Anogenital Squamous Terminology recommendations. This opens the possibility of investigating selective treatment of advanced transforming HSILs caused by hrHPV, and a 'wait and see' policy for productive HSILs. What's already known about this topic? For preventing anal cancer in high-risk populations, all patients with high-grade squamous intraepithelial lesions (HSILs) are treated, even though this group of lesions is heterogeneous, the histology is variable and regression is frequent. What does this study add? By adding human papillomavirus (HPV) E4 immunohistochemistry to p16 INK4a (p16), and grading expression of both markers, different biomarker expression patterns that reflect the heterogeneity of HSILs can be identified. Moreover, p16/E4 staining can separate high-risk HPV-associated HSILs into productive and more advanced transforming lesions, providing a potential basis for selective treatment.

Experimental Evidence for Transverse Wobbling in

New rotational bands built on the ν(h_{11/2}) configuration have been identified in ^{105}Pd. Two bands built on this configuration show the characteristics of transverse wobbling: the ΔI=1 transitions between them have a predominant E2 component and the wobbling energy decreases with increasing spin. The properties of the observed wobbling bands are in good agreement with theoretical results obtained using constrained triaxial covariant density functional theory and quantum particle rotor model calculations. This provides the first experimental evidence for transverse wobbling bands based on a one-neutron configuration, and also represents the first observation of wobbling motion in the A∼100 mass region.

Exploring the Structure of the Bound Proton with Deeply Virtual Compton Scattering.

In the past two decades, deeply virtual Compton scattering of electrons has been successfully used to advance our knowledge of the partonic structure of the free proton and investigate correlations between the transverse position and the longitudinal momentum of quarks inside the nucleon. Meanwhile, the structure of bound nucleons in nuclei has been studied in inclusive deep-inelastic lepton scattering experiments off nuclear targets, showing a significant difference in longitudinal momentum distribution of quarks inside the bound nucleon, known as the EMC effect. In this Letter, we report the first beam spin asymmetry (BSA) measurement of exclusive deeply virtual Compton scattering off a proton bound in ^{4}He. The data used here were accumulated using a 6 GeV longitudinally polarized electron beam incident on a pressurized ^{4}He gaseous target placed within the CLAS spectrometer in Hall-B at the Thomas Jefferson National Accelerator Facility. The azimuthal angle (ϕ) dependence of the BSA was studied in a wide range of virtual photon and scattered proton kinematics. The Q^{2}, x_{B}, and t dependencies of the BSA on the bound proton are compared with those on the free proton. In the whole kinematical region of our measurements, the BSA on the bound proton is smaller by 20% to 40%, indicating possible medium modification of its partonic structure.

Studies of pear-shaped nuclei using accelerated radioactive beams.

There is strong circumstantial evidence that certain heavy, unstable atomic nuclei are 'octupole deformed', that is, distorted into a pear shape. This contrasts with the more prevalent rugby-ball shape of nuclei with reflection-symmetric, quadrupole deformations. The elusive octupole deformed nuclei are of importance for nuclear structure theory, and also in searches for physics beyond the standard model; any measurable electric-dipole moment (a signature of the latter) is expected to be amplified in such nuclei. Here we determine electric octupole transition strengths (a direct measure of octupole correlations) for short-lived isotopes of radon and radium. Coulomb excitation experiments were performed using accelerated beams of heavy, radioactive ions. Our data on (220)Rn and (224)Ra show clear evidence for stronger octupole deformation in the latter. The results enable discrimination between differing theoretical approaches to octupole correlations, and help to constrain suitable candidates for experimental studies of atomic electric-dipole moments that might reveal extensions to the standard model.

Measurement of extravascular lung water to diagnose severe reperfusion lung injury following pulmonary endarterectomy: a prospective cohort clinical validation study.

The measurement of extravascular lung water is a relatively new technology which has not yet been well validated as a clinically useful tool. We studied its utility in patients undergoing pulmonary endarterectomy as they frequently suffer reperfusion lung injury and associated oedematous lungs. Such patients are therefore ideal for evaluating this new monitor. We performed a prospective observational cohort study during which extravascular lung water index measurements were taken before and immediately after surgery and postoperatively in intensive care. Data were analysed for 57 patients; 21 patients (37%) experienced severe reperfusion lung injury. The first extravascular lung water index measurement after cardiopulmonary bypass failed to predict severe reperfusion lung injury, area under the receiver operating characteristic curve 0.59 (95%CI 0.44-0.74). On intensive care, extravascular lung water index correlated most strongly at 36 h, area under the receiver operating characteristic curve 0.90 (95%CI 0.80-1.00). Peri-operative extravascular lung water index is not a useful measure to predict severe reperfusion lung injury after pulmonary endarterectomy, however, it does allow monitoring and measurement during the postoperative period. This study implies that extravascular lung water index can be used to directly assess pulmonary fluid overload and that monitoring patients by measuring extravascular lung water index during their intensive care stay is useful and correlates with their clinical course. This may allow directed, pre-empted therapy to attenuate the effects and improve patient outcomes and should prompt further studies.

Vox Sanguinis International Forum on the use of prehospital blood products and pharmaceuticals in the treatment of patients with traumatic haemorrhage.

While specific practices and transported blood products vary around the world, most of the respondents in this International Forum transported at least one blood product for the transfusion to bleeding patients en route to the hospital. The most commonly carried product was RBCs, while the use of whole blood will likely increase given the recent reports of its successful use in the civilian setting, and because of the change in the AABB's Standards regulating its use. It will be interesting to see if plasma use in the prehospital setting becomes more widely used given today's enhanced appreciated of the coagulopathy of trauma and plasma's beneficial effect in reversing it, and if blood products are transported to the scene of injury by more vehicles, that is, not just predominantly in helicopters. It was not surprising that TXA is being widely administered as close to the time of injury as possible given its potential benefit in these patients. This International Forum highlights the importance of focusing attention on prehospital transfusion management with a need to further high­quality research in this area to guide optimal resuscitation strategies.

Risk Differences Between Prediabetes And Diabetes According To Breast Cancer Molecular Subtypes.

Hyperglycemia and hyperinsulinemia may play a role in breast carcinogenesis and prediabetes and diabetes have been associated with increased breast cancer (BC) risk. However, whether BC molecular subtypes may modify these associations is less clear. We therefore investigated these associations in all cases and by BC molecular subtypes among women living in Southern Italy. Cases were 557 patients with non-metastatic incident BC and controls were 592 outpatients enrolled during the same period as cases and in the same hospital for skin-related non-malignant conditions. Adjusted multivariate logistic regression models were built to assess the risks of developing BC in the presence of prediabetes or diabetes. The analyses were repeated by strata of BC molecular subtypes: Luminal A, Luminal B, HER2+, and Triple Negative (TN). Prediabetes and diabetes were significantly associated with higher BC incidence after controlling for known risk factors (OR = 1.94, 95% CI 1.32-2.87 and OR = 2.46, 95% CI 1.38-4.37, respectively). Similar results were seen in Luminal A and B while in the TN subtype only prediabetes was associated with BC (OR = 2.43, 95% CI 1.11-5.32). Among HER2+ patients, only diabetes was significantly associated with BC risk (OR = 3.04, 95% CI 1.24-7.47). Furthermore, when postmenopausal HER2+ was split into hormone receptor positive versus negative, the association with diabetes remained significant only in the former (OR = 5.13, 95% CI 1.53-17.22). These results suggest that prediabetes and diabetes are strongly associated with BC incidence and that these metabolic conditions may be more relevant in the presence of breast cancer molecular subtypes with positive hormone receptors. J. Cell. Physiol. 232: 1144-1150, 2017. © 2016 Wiley Periodicals, Inc.

Discovery of

In this Letter, the observation of two previously unknown isotopes is presented for the first time: ^{72}Rb with 14 observed events and ^{77}Zr with one observed event. From the nonobservation of the less proton-rich nucleus ^{73}Rb, we derive an upper limit for the ground-state half-life of 81 ns, consistent with the previous upper limit of 30 ns. For ^{72}Rb, we have measured a half-life of 103(22) ns. This observation of a relatively long-lived odd-odd nucleus, ^{72}Rb, with a less exotic odd-even neighbor, ^{73}Rb, being unbound shows the diffuseness of the proton drip line and the possibility of sandbanks to exist beyond it. The ^{72}Rb half-life is consistent with a 5^{+}→5/2^{-} proton decay with an energy of 800-900 keV, in agreement with the atomic mass evaluation proton-separation energy as well as results from the finite-range droplet model and shell model calculations using the GXPF1A interaction. However, we cannot explicitly exclude the possibility of a proton transition between 9^{+}(^{72}Rb)→9/2^{+}(^{71}Kr) isomeric states with a broken mirror symmetry. These results imply that ^{72}Kr is a strong waiting point in x-ray burst rp-process scenarios.

First Exclusive Measurement of Deeply Virtual Compton Scattering off

We report on the first measurement of the beam-spin asymmetry in the exclusive process of coherent deeply virtual Compton scattering off a nucleus. The experiment uses the 6 GeV electron beam from the Continuous Electron Beam Accelerator Facility (CEBAF) accelerator at Jefferson Lab incident on a pressurized ^{4}He gaseous target placed in front of the CEBAF Large Acceptance Spectrometer (CLAS). The scattered electron is detected by CLAS and the photon by a dedicated electromagnetic calorimeter at forward angles. To ensure the exclusivity of the process, a specially designed radial time projection chamber is used to detect the recoiling ^{4}He nuclei. We measure beam-spin asymmetries larger than those observed on the free proton in the same kinematic domain. From these, we are able to extract, in a model-independent way, the real and imaginary parts of the only ^{4}He Compton form factor, H_{A}. This first measurement of coherent deeply virtual Compton scattering on the ^{4}He nucleus, with a fully exclusive final state via nuclear recoil tagging, leads the way toward 3D imaging of the partonic structure of nuclei.

HPV testing in first-void urine provides sensitivity for CIN2+ detection comparable with a smear taken by a clinician or a brush-based self-sample: cross-sectional data from a triage population.

OBJECTIVE: To compare the sensitivity of high-risk human papillomavirus (hrHPV) and genotype detection in self-collected urine samples in the morning (U1), and later on (U2), brush-based self-samples (SS), and clinician-taken smears (CTS) for detecting cervical intraepithelial neoplasia grade 2+ (CIN2+) in a colposcopic referral population. DESIGN: Cross-sectional single-centre study. SETTING: A colposcopy clinic in Spain. POPULATION: A cohort of 113 women referred for colposcopy after an abnormal Pap smear. METHODS: Women undergoing colposcopy with biopsy for abnormal Pap smears were sent a device (Colli-Pee™, Novosanis, Wijnegem, Belgium) to collect U1 on the morning of colposcopy. U2, CTS, and SS (Evalyn brush™, Rovers Medical Devices B.V., Oss, the Netherlands) were also analysed. All samples were tested for HPV DNA using the analytically sensitive SPF10-DEIA-LiPA25 assay and the clinically validated GP5+/6+-EIA-LMNX. MAIN OUTCOME MEASURES: Histologically confirmed CIN2+ and hrHPV positivity for 14 high-risk HPV types. RESULTS: Samples from 91 patients were analysed. All CIN3 cases (n = 6) tested positive for hrHPV in CTS, SS, U1, and U2 with both HPV assays. Sensitivity for CIN2+ with the SPF10 system was 100, 100, 95, and 100%, respectively. With the GP5+/6+ assay, sensitivity was 95% in all sample types. The sensitivities and specificities for both tests on each of the sample types did not significantly differ. There was 10-14% discordance on hrHPV genotype. CONCLUSIONS: CIN2+ detection using HPV testing of U1 shows a sensitivity similar to that of CTS or brush-based SS, and is convenient. There was substantial to almost excellent agreement between all samples on genotype with both hrHPV assays. There was no advantage in testing U1 compared with U2 samples. TWEETABLE ABSTRACT: Similar CIN2+ sensitivity for HPV testing in first-void urine, physician-taken smear and brush-based self-sample.

Spectroscopic Quadrupole Moments in {96,98}Sr: Evidence for Shape Coexistence in Neutron-Rich Strontium Isotopes at N=60.

Neutron-rich {96,98}Sr isotopes have been investigated by safe Coulomb excitation of radioactive beams at the REX-ISOLDE facility. Reduced transition probabilities and spectroscopic quadrupole moments have been extracted from the differential Coulomb excitation cross sections. These results allow, for the first time, the drawing of definite conclusions about the shape coexistence of highly deformed prolate and spherical configurations. In particular, a very small mixing between the coexisting states is observed, contrary to other mass regions where strong mixing is present. Experimental results have been compared to beyond-mean-field calculations using the Gogny D1S interaction in a five-dimensional collective Hamiltonian formalism, which reproduce the shape change at N=60.

Erratum: Spectroscopic Quadrupole Moments in

This corrects the article DOI: 10.1103/PhysRevLett.116.022701.