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Transmission spectroscopy of exoplanets has revealed signatures of water vapor, aerosols, and alkali metals in a few dozen exoplanet atmospheres. However, these previous inferences with the Hubble and Spitzer Space Telescopes were hindered by the observations' relatively narrow wavelength range and spectral resolving power, which precluded the unambiguous identification of other chemical species$-$in particular the primary carbon-bearing molecules. Here we report a broad-wavelength 0.5-5.5 $\mu$m atmospheric transmission spectrum of WASP-39 b, a 1200 K, roughly Saturn-mass, Jupiter-radius exoplanet, measured with JWST NIRSpec's PRISM mode as part of the JWST Transiting Exoplanet Community Early Release Science Team program. We robustly detect multiple chemical species at high significance, including Na (19$\sigma$), H$_2$O (33$\sigma$), CO$_2$ (28$\sigma$), and CO (7$\sigma$). The non-detection of CH$_4$, combined with a strong CO$_2$ feature, favours atmospheric models with a super-solar atmospheric metallicity. An unanticipated absorption feature at 4$\mu$m is best explained by SO$_2$ (2.7$\sigma$), which could be a tracer of atmospheric photochemistry. These observations demonstrate JWST's sensitivity to a rich diversity of exoplanet compositions and chemical processes., Comment: 41 pages, 4 main figures, 10 extended data figures, 4 tables. Under review in Nature

Branched Pt nanoparticles represent an exciting class of nanomaterials with high surface areas suitable for applications in electrocatalysis. Introducing a second metal can enhance performance and reduce cost. External factors such as capping agents and temperature have been used to offer insights into nanopod formation and to encourage their kinetic evolution. More recently, nanodendrites have been reported, though synthesis has generally been empirical; making controlled variation of morphology while maintaining bimetallic composition an elusive target. We report the combination of Pt with Fe under a range of conditions, yielding individually bimetallic nanoparticles whose construction sheds new light on nanopod and/or nanodendrite formation. Fine control of metal precursor reduction through modulating capping agents, reagents, and temperature initially directs nanopod synthesis. Morphology control is retained while composition is then varied from Pt-rich to Pt-poor. Additionally, conditions are identified that promote the collision-based branching of nanopod arms. This allows synthesis to be redirected for the selective growth of compositionally controlled nanodendrites in predictable fashion.

High-risk groups, including Indigenous people, are at risk of severe COVID-19. Here we found that Australian First Nations peoples elicit effective immune responses to COVID-19 BNT162b2 vaccination, including neutralizing antibodies, receptor-binding domain (RBD) antibodies, SARS-CoV-2 spike-specific B cells, and CD4+ and CD8+ T cells. In First Nations participants, RBD IgG antibody titers were correlated with body mass index and negatively correlated with age. Reduced RBD antibodies, spike-specific B cells and follicular helper T cells were found in vaccinated participants with chronic conditions (diabetes, renal disease) and were strongly associated with altered glycosylation of IgG and increased interleukin-18 levels in the plasma. These immune perturbations were also found in non-Indigenous people with comorbidities, indicating that they were related to comorbidities rather than ethnicity. However, our study is of a great importance to First Nations peoples who have disproportionate rates of chronic comorbidities and provides evidence of robust immune responses after COVID-19 vaccination in Indigenous people.

We present a study of rotation across 30 square degrees of the Orion Star-forming Complex, following a $\sim$200 d photometric monitoring campaign by the Next Generation Transit Survey (NGTS). From 5749 light curves of Orion members, we report periodic signatures for 2268 objects and analyse rotation period distributions as a function of colour for 1789 stars with spectral types F0$-$M5. We select candidate members of Orion using $\textit{Gaia}$ data and assign our targets to kinematic sub-groups. We correct for interstellar extinction on a star-by-star basis and determine stellar and cluster ages using magnetic and non-magnetic stellar evolutionary models. Rotation periods generally lie in the range 1$-$10 d, with only 1.5 per cent of classical T Tauri stars or Class I/II young stellar objects rotating with periods shorter than 1.8 d, compared with 14 per cent of weak-line T Tauri stars or Class III objects. In period$-$colour space, the rotation period distribution moves towards shorter periods among low-mass (>M2) stars of age 3$-$6 Myr, compared with those at 1$-$3 Myr, with no periods longer than 10 d for stars later than M3.5. This could reflect a mass-dependence for the dispersal of circumstellar discs. Finally, we suggest that the turnover (from increasing to decreasing periods) in the period$-$colour distributions may occur at lower mass for the older-aged population: $\sim$K5 spectral type at 1$-$3 Myr shifting to $\sim$M1 at 3$-$6 Myr., This article has been accepted for publication in Monthly Notices of the Royal Astronomical Society. Published by Oxford University Press on behalf of the Royal Astronomical Society. 20 pages. 21 figures

Accelerating scramjet engines could efficiently propel the second stage of an access to space system. A scramjet engine designed to accelerate from Mach 5 to 10 requires geometric features to assist performance at either end of the trajectory, which negatively affects the performance at the opposite end. This work discusses the necessity of these features and their implications on performance. A fueling configuration for the high Mach number operation of an accelerator scramjet is introduced. This injection scheme was designed for a ground test model, at small scale. The high Mach number performance of the engine is categorized at on- and off-design conditions. Its extension to a full-scale engine was also investigated. The full-scale engine generates thrust at Mach 10, despite a reduced area-ratio nozzle. Across all conditions simulated, the engine and fueling scheme has robust performance, although it required a reduction of inlet fueling at scale.

In this article, we look at how competition is presented in the traditional mini tennis lesson, finding that it typically occurs once, at the end of the session. We then explore some of the limitations associated with competition in this format. Following that, we discuss the importance of developing competitive capabilities, and propose an alternative way of approaching the mini tennis lesson to provide more opportunity for competition while systematically developing tactical and technical skills in a manner consistent with findings from skill acquisition research. This methodological approach, we suggest, provides a more fertile environment in which to develop competitive performers alongside the tactical and technical performance factors.

In this paper, we present observations of two high-resolution transit datasets obtained with ESPRESSO of the bloated sub-Saturn planet WASP-131~b. We have simultaneous photometric observations with NGTS and EulerCam. In addition, we utilised photometric lightcurves from {\tess}, WASP, EulerCam and TRAPPIST of multiple transits to fit for the planetary parameters and update the ephemeris. We spatially resolve the stellar surface of WASP-131 utilising the Reloaded Rossiter McLaughlin technique to search for centre-to-limb convective variations, stellar differential rotation, and to determine the star-planet obliquity for the first time. We find WASP-131 is misaligned on a nearly retrograde orbit with a projected obliquity of $\lambda = 162.4\substack{+1.3 \\ -1.2}^{\circ}$. In addition, we determined a stellar differential rotation shear of $\alpha = 0.61 \pm 0.06$ and disentangled the stellar inclination ($i_* = 40.9\substack{+13.3 \\ -8.5}^{\circ}$) from the projected rotational velocity, resulting in an equatorial velocity of $v_{\rm{eq}} = 7.7\substack{+1.5 \\ -1.3}$~km s$^{-1}$. In turn, we determined the true 3D obliquity of $\psi = 123.7\substack{+12.8 \\ -8.0}^{\circ}$, meaning the planet is on a perpendicular/polar orbit. Therefore, we explored possible mechanisms for the planetary system's formation and evolution. Finally, we searched for centre-to-limb convective variations where there was a null detection, indicating that centre-to-limb convective variations are not prominent in this star or are hidden within red noise., Comment: 15 Pages, 10 Figures and 4 Tables Accepted for Publication in MNRAS. arXiv admin note: text overlap with arXiv:2207.10127

We model the evaporation histories of the three planets around K2-136, a K-dwarf in the Hyades open cluster with an age of 700 Myr. The star hosts three transiting planets, with radii of 1.0, 3.0 and 1.5 Earth radii, where the middle planet lies above the radius-period valley and the inner and outer planets are below. We use an XMM-Newton observation to measure the XUV radiation environment of the planets, finding that the X-ray activity of K2-136 is lower than predicted by models but typical of similar Hyades members. We estimate the internal structure of each planet, and model their evaporation histories using a range of structure and atmospheric escape formulations. While the precise X-ray irradiation history of the system may be uncertain, we exploit the fact that the three planets must have shared the same history. We find that the Earth-sized K2-136b is most likely rocky, with any primordial gaseous envelope being lost within a few Myr. The sub-Neptune, K2-136c, has an envelope contributing 1-1.7% of its mass that is stable against evaporation thanks to the high mass of its rocky core, whilst the super-Earth, K2-136d, must have a mass at the upper end of the allowed range in order to retain any of its envelope. Our results are consistent with all three planets beginning as sub-Neptunes that have since been sculpted by atmospheric evaporation to their current states, stripping the envelope from planet b and removing most from planet d whilst preserving planet c above the radius-period valley., Comment: Accepted for publication on MNRAS

This article considers the international laws applicable to irresponsible state behaviour in cyberspace through the lens of the problem of election hacking. The rule of sovereignty has taken centre stage in these discussions and is said to be preferred to the non-intervention rule because it evades the problem of coercion. Proponents of the cyber rule of sovereignty contend that there is such a rule; opponents reject the existence of the rule as a matter of existing law. The objective here is to explore the methodologies involved in the identification of the cyber rule of sovereignty under customary international law. The work first frames the debate in the language of regulative and constitutive rules, allowing us to show that a regulative rule of sovereignty can, logically, and necessarily, be deduced from the constitutive rule of sovereignty. The content of the regulative rule can also be deduced from the constitutive rule of sovereignty, but it has a more limited scope than claimed by the proponents of the rule, notably the Tallinn Manual 2.0. The rule of sovereignty prohibits state cyber operations carried out on the territory of the target state and remote cyber operations which involve the exercise of sovereign authority on that territory, e.g., police evidence-gathering operations. The rule of sovereignty does not, however, prohibit other remote, ex situ state cyber operations, even those targeting ICTs used for governmental functions, including the conduct of elections. The rule of sovereignty is not, then, the solution to the problem of election hacking.

The past few decades have seen hate crime receive significant academic attention. Yet, while academics have researched the many aspects of hate crime, gaps still remain in the evidence base. This paper seeks to examine one of those gaps: the relationship between hate crime and violent extremism. To examine this relationship, the paper utilised a Rapid Evidence Assessment methodology. The authors searched multiple online databases with a focus on post ‘9/11’ literature through to December 2020, yielding a total of 38 articles. The research explored components of violent extremism and their similarities and differences to hate crime. Findings showed that while there is a relationship between hate crime and violent extremism, the nature and extent of this nexus is quite specific. Accordingly, by targeting the similarities between the two, practices and interventions that seek to prevent one may also be applied to the other.

Airtankers are commonly used for initial attack (IA) to reduce the likelihood of wildland fires escaping containment efforts. We examined IA airtanker dispatch decisions for forest fires in Ontario, Canada, through an analysis of historical fire records from 2001 to 2019. A hurdle modelling approach that predicts the probability of airtanker(s) being dispatched and then the number of airtankers sent was used. Two different hurdle models were considered depending on the timing of the information available to the decision maker: a “fire report model” based upon the information available when a fire is first reported, and an “initial attack model” using information available at the time IA action began. Both models indicated that the most influential covariates for airtanker dispatch are the fire weather index, fuel volatility, observed fire rate of spread, fire size at IA, and cause of ignition. When evaluating the predictive ability of the models on a validation data set, the “initial attack model” performed better than the “fire report model”. Our models generally perform well when predicting none, one, or two airtankers on IA, but they generally underpredict when more than two airtankers are dispatched, which suggests risk-averse decision-making in fire management resource dispatching.

Background and Objective: Postoperative pain is frequently reported following scleral buckle (SB) surgery. This study assessed the efficacy of perioperative dexamethasone on postoperative pain and opioid use following SB. Materials and Methods: Forty-five patients with rhegmatogenous retinal detachments undergoing SB or SB and pars plana vitrectomy were randomly assigned to either standard care of postoperative oral acetaminophen and oxycodone/acetaminophen as needed or standard care plus 8 mg single-dose peri-operative intravenous dexamethasone. A questionnaire was administered on postoperative days 0, 1, and 7 to determine visual analog scale 0 to 10 pain score and number of opioid tablets consumed. Results: Mean visual analog scale score and opioid use were significantly lower in the dexamethasone group on postoperative day 0 compared with control (2.76 ± 1.96 vs 5.64 ± 3.40, P = 0.002; 0.41 ± 0.92 vs 1.34 ± 1.43, P = 0.016). The dexamethasone group also demonstrated significantly lower total opioid use (0.97 ± 1.88 vs 3.69 ± 5.32, P = 0.047). No significant differences in pain score or opioid use were observed on days 1 or 7 ( P = 0.078; P = 0.311; P = 0.326; P = 0.334). Conclusion: Single-dose intravenous dexamethasone following SB can significantly reduce postoperative pain and opioid use. [ Ophthalmic Surg Lasers Imaging Retina 2023;54:238–242.]

Biodiesel production from low cost, inedible oil represents an increasingly important target for reasons of both sustainability and cost. In this work, we comprehensively verify the batch reproducibility of a sulfonic acid functionalized carbonaceous material (SAFACAM) as catalyst for biodiesel production from inedible feedstock Jatropha curcas oil (JCO) using a heterogeneous biomass-based carbonaceous solid acid catalyst. The current catalyst benefits the environment through its atom-efficient, one-pot preparation from an abundant natural biomass derivative (glucose) and has the potential to reduce the overall biodiesel production cost by converting inexpensive raw materials. In this context, JCO has emerged as a crop of interest to energy sector, potentially providing a reliable and renewable energy source for many countries. Through a central composite design (CCD) approach using response surface methodology (RSM), a 98.70.6 % conversion of biodiesel is achieved (methanol-to-oil molar ratio 20:1, reaction time 50 mins, reaction temperature 120 °C and catalyst loading 9 wt. % (with respect to oil)). The chemically satisfactory composition of the biodiesel product has been verified, the reusability of catalyst has been tested, and a significant enhancement in performance when using microwave heating demonstrated. An 83.00.8 % conversion of JCO is reported in the fifth cycle of reuse.

Glycine is a major neurotransmitter involved in several fundamental neuronal processes. The identity of the metabotropic receptor mediating slow neuromodulatory effects of glycine is unknown. We identified an orphan G protein–coupled receptor, GPR158, as a metabotropic glycine receptor (mGlyR). Glycine and a related modulator, taurine, directly bind to a Cache domain of GPR158, and this event inhibits the activity of the intracellular signaling complex regulator of G protein signaling 7–G protein β5 (RGS7-Gβ5), which is associated with the receptor. Glycine signals through mGlyR to inhibit production of the second messenger adenosine 3′,5′-monophosphate. We further show that glycine, but not taurine, acts through mGlyR to regulate neuronal excitability in cortical neurons. These results identify a major neuromodulatory system involved in mediating metabotropic effects of glycine, with implications for understanding cognition and affective states.

Purpose This study provides further insight into the experiences of five men who have committed sexual offences, with intellectual disabilities and have been recalled back to prison. The purpose of this paper is to increase professional knowledge to assist with improving working practices that support the reintegration of individuals convicted of sexual offences and with intellectual disabilities, back into the community. Design/methodology/approach Interview data was analysed using interpretative phenomenological analysis, to identify the key issues associated with criminal justice services. Findings The following superordinate themes were identified: “The label that sticks” and “Probation officer dependency”. Research limitations/implications The key implications of the findings were the high level of dependency individuals had on their probation officers and the impact that this relationship had on the overall experience of recall. The stigma of the label “sex offender” was also found to have a profound impact on individuals’ feelings of safety and their future progression. Originality/value Research exploring the experiences of individuals convicted for sexual offences and with intellectual disabilities, being recalled back to prison, is limited. Future recommendations of how practice could be improved to better support responsivity needs of this group and to create a more positive self-identity are discussed.

The PACIFIC trial showed a survival benefit with durvalumab through five years in stage III unresectable non-small cell lung cancer (NSCLC). However, optimal use of imaging to detect disease progression remains unclearly defined for this population. An expert working group convened to consider available evidence and clinical experience and develop recommendations for follow-up imaging after concurrent chemotherapy and radiation therapy (CRT). Voting on agreement was conducted anonymously via online survey. Follow-up imaging was recommended for all suitable patients after CRT completion regardless of whether durvalumab is received. Imaging should occur every 3 months in Year 1, at least every 6 months in Year 2, and at least every 12 months in Years 3–5. Contrast computed tomography was preferred; routine brain imaging was not recommended for asymptomatic patients. The medical oncologist should follow-up during Year 1 of durvalumab therapy, with radiation oncologist involvement if pneumonitis is suspected; medical and radiation oncologists can subsequently alternate follow-up. Some patients can transition to the family physician/community primary care team at the end of Year 2. In Years 1–5, patients should receive information regarding smoking cessation, comorbidity management, vaccinations, and general follow-up care. These recommendations provide guidance on follow-up imaging for patients with stage III unresectable NSCLC whether or not they receive durvalumab consolidation therapy.

Background The transition to university and resultant social support network disruption can be detrimental to the mental health of university students. As the need for mental health support is becoming increasingly prevalent in students, identification of factors associated with poorer outcomes is a priority. Changes in social functioning have a bi-directional relationship with mental health, however it is not clear how such measures may be related to effectiveness of psychological treatments. Methods Growth mixture models were estimated on a sample of 5221 students treated in routine mental health services to identify different trajectories of change in self-rated impairment in social leisure activities and close relationships during the course of treatment. Multinomial regression explored associations between trajectory classes and treatment outcomes. Results Five trajectory classes were identified for social leisure activity impairment while three classes were identified for close relationship impairment. In both measures most students remained mildly impaired. Other trajectories included severe impairment with limited improvement, severe impairment with delayed improvement, and, in social leisure activities only, rapid improvement, and deterioration. Trajectories of improvement were associated with positive treatment outcomes while trajectories of worsening or stable severe impairment were associated with negative treatment outcomes. Conclusions Changes in social functioning impairment are associated with psychological treatment outcomes in students, suggesting that these changes may be associated with treatment effectiveness as well as recovery experiences. Future research should seek to establish whether a causal link exists to understand whether integrating social support within psychological treatment may bring additional benefit for students.

Background There is limited published data on the stability of calcitonin, chromogranin A, thyroglobulin and anti-thyroglobulin antibodies in serum. The aim of this study was to determine stability at three temperature conditions over 7 days, reflecting current laboratory practices. Methods Surplus serum was stored at room temperature, refrigerated and in the freezer; for 1, 3, 5 and 7 days. Samples were analysed in batch and analyte concentrations compared to that of a baseline sample. Measurement Uncertainty of the assay was used to determine the Maximal Permissible Difference and thus the stability of the analyte. Results Calcitonin was found to be stable for at least 7 days in the freezer but only 24 h refrigerated. Chromogranin A was stable for 3 days when refrigerated and only 24 h at room temperature. Thyroglobulin and anti-thyroglobulin antibodies were stable under all conditions for 7 days. Conclusion This study has enabled the laboratory to increase the add-on time limit of Chromogranin A to 3 days, and up to 60 min for calcitonin and inform optimal storage and transportation conditions for referring specimens.

Background: Imlunestrant is a novel, orally bioavailable selective estrogen receptor degrader (SERD) with pure antagonistic properties that result in sustained inhibition of estrogen receptor (ER)-dependent gene transcription and cell growth. In a phase 1 study, imlunestrant monotherapy showed favourable safety, pharmacokinetics (PK) and preliminary efficacy in heavily pre-treated ER-positive (ER+) advanced breast cancer patients (Jhaveri ASCO 2022). Here, we present pharmacodynamic (PD) data from the preoperative window of opportunity (WOO) study (EMBER-2, NCT04647487), evaluating the biological activity of imlunestrant monotherapy in ER+, HER2-negative (HER2-) early breast cancer (EBC). Methods: Post-menopausal women with stage I–III operable ER+ (>50%) or Allred score >5, HER2- untreated EBC ≥1 cm in diameter were randomized 1:1 to imlunestrant 400 mg once daily (QD) or imlunestrant 800 mg QD for 15 days (treatment window of -2 to +7 days) up to the surgery date. Pre- and on-treatment tumor samples were compared for changes in PD biomarkers. Primary study objective was change in ER expression (measured by IHC and quantified by H-score). Secondary objectives were change in progesterone receptor (PR) expression (measured by IHC and quantified by H-score) and Ki-67 (measured by IHC and expressed by percentage positive scoring) along with evaluation of safety and tolerability. Results: From Apr 28, 2021, to Mar 11, 2022, 58 patients were enrolled of which 54 were biomarker-evaluable for ER expression (400 mg: n = 28; 800 mg: n = 26). Patient demographics and tumor characteristics for all enrolled patients were similar across cohorts, with a median age of 64 years (50-83), 72% invasive ductal carcinoma (IDC), 28% invasive lobular carcinoma (ILC), 59% stage I, 36% stage II and 5% stage III disease. 91% of the patients had a compliance rate higher than 80%. Among biomarker evaluable patients, relative reduction in PD biomarkers after a median of 15 days (range 13 to 23 days) of treatment are presented in Table 1. There was no significant difference in PD biomarker modulation noted between the two imlunestrant doses (400 mg vs 800 mg) or based on tumor histology (IDC, ILC). Imlunestrant was well tolerated. There were no discontinuations due to adverse events (AEs). Treatment-related AEs (TRAEs) were mainly grade 1, most commonly: fatigue (10%), diarrhea (9%), hot flushes (7%), and nausea (5%). There were no TRAEs of diarrhea and nausea observed at the 400 mg dose. No grade 3 or higher TRAEs were reported. Conclusion: Imlunestrant demonstrated evidence of target engagement along with consistent biological activity across all evaluated dose levels and was well tolerated in an EBC population, further supporting continued adjuvant development in the ongoing EMBER-4 study. Additional biomarker analyses for the EMBER-2 study are also planned. Table 1. Relative reduction in PD biomarkers from Baseline to Day 15 Citation Format: Patrick Neven, Nicole Stahl, Maria Vidal, Miguel Martín, Nadia Harbeck, Peter A. Kaufman, Francois-Clement Bidard, Peter A. Fasching, Philippe Aftimos, Erika Hamilton, Stacey Carter, Peter Schmid, Duncan Wheatley, Manali Bhave, Kelly K. Hunt, Swati A. Kulkarni, Roohi Ismail-Khan, Claudia Karacsonyi, Shawn T. Estrem, Umut Ozbek, Bastien Nguyen, Eva Ciruelos. A preoperative window-of-opportunity study of imlunestrant in estrogen receptor-positive, HER2-negative early breast cancer: Results from the EMBER-2 study. [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P6-10-06.

Introduction: Axillary lymph node dissection (ALND) is associated with significant morbidity. Randomised data [1,2] suggest that axillary radiotherapy (RT), or no further axillary treatment beyond sentinel node biopsy (SNB) may be safe. There are very few studies to guide the management of preoperatively diagnosed lymph node metastases either in the context of neoadjuvant chemotherapy (NACT) or direct to surgery. The current UK recommendation is for ALND. In 2015 our policy changed to RT for carefully selected patients after MDT discussion. These data look at axillary recurrence for those patients having axillary RT Methods: Data were retrospectively collected on patients with preoperatively diagnosed lymph node metastases between January 2016 and December 2020. Patients undergoing surgery with a curative intent were included. The decision to offer axillary RT was made in the MDT based on clinical and radiological findings and the burden of disease in the axillary sample. Axillary recurrence was defined as disease recurring in the axilla with no distant disease. Results: Date were collected on 132 patients. Demographics and tumour status are outlined in Table 1. 55% of patients had neoadjuvant chemotherapy with a 52% path CR in the axilla. Table 2 gives the results for the axillary RT group. During the same time period 25 patient had ALND. Of those 2 (8%) had isolated LN recurrence. 18 patients had axillary RT following positive SLN after NACT. There was a single patient with axillary recurrence in this group. Conclusion: In the absence of randomised data to guide practice, these data show that in selected patients axillary radiotherapy is safe after axillary node sampling. The decision should be based on axillary burden, tumour biology, MDT and patient discussion. We await with interest the results of the Alliance A011202 trial to guide practice in patients having NACT in N1 disease. [1] Donker M, van Tienhoven G, Straver ME, Meijnen P, van de Velde CJ, Mansel RE, Cataliotti L, Westenberg AH, Klinkenbijl JH, Orzalesi L, Bouma WH, van der Mijle HC, Nieuwenhuijzen GA, Veltkamp SC, Slaets L, Duez NJ, de Graaf PW, van Dalen T, Marinelli A, Rijna H, Snoj M, Bundred NJ, Merkus JW, Belkacemi Y, Petignat P, Schinagl DA, Coens C, Messina CG, Bogaerts J, Rutgers EJ. Radiotherapy or surgery of the axilla after a positive sentinel node in breast cancer (EORTC 10981-22023 AMAROS): a randomised, multicentre, open-label, phase 3 non-inferiority trial. Lancet Oncol. 2014 Nov;15(12):1303-10. doi: 10.1016/S1470-2045(14)70460-7. [2] Giuliano, A.E.; Ballman, K.; McCall, L.; Beitsch, P.; Whitworth, P.W.; Blumencranz, P.; Leitch, A.M.; Saha, S.; Morrow, M.; Hunt, K.K. Locoregional Recurrence After Sentinel Lymph Node Dissection With or Without Axillary Dissection in Patients With Sentinel Lymph Node Metastases: Long-term Follow-up From the American College of Surgeons Oncology Group (Alliance) ACOSOG Z0011 Randomized Trial. Ann. Surg. 2016, 264, 413–420 Table 1. Demographics and tumour status. Table 2. Patients having Axillary RT. Citation Format: Hamza A. Arabiyat, Iain Brown, Philip Drew, Rachel English, Mona Sulieman, Imran Abbas, Duncan Wheatley, Kali Potiszil, Alastair Thomson, Polly King. Axillary radiotherapy in selected patients with a preoperative diagnosis of lymph node involvement is a safe alternative to axillary lymph node dissection [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P1-10-17.

Contains fulltext : 290886.pdf (Publisher’s version ) (Closed access) This guideline will inform physicians, nurses, dieticians, pharmacists, caregivers and other home parenteral nutrition (HPN) providers, as well as healthcare administrators and policy makers, about appropriate and safe HPN provision. This guideline will also inform patients requiring HPN. The guideline is based on previous published guidelines and provides an update of current evidence and expert opinion; it consists of 71 recommendations that address the indications for HPN, central venous access device (CVAD) and infusion pump, infusion catheter and CVAD site care, nutritional admixtures, program monitoring and management. Meta-analyses, systematic reviews and single clinical trials based on clinical questions were searched according to the PICO format. The evidence was evaluated and used to develop clinical recommendations implementing Scottish Intercollegiate Guidelines Network methodology. The guideline was commissioned and financially supported by ESPEN and members of the guideline group were selected by ESPEN.

Background: For patients who are node positive at presentation and are found to have a complete nodal tumour response (ypN0) post-neoadjuvant chemotherapy (NACT), we do not yet know whether local axillary therapy can be modified based on the response to NACT. ATNEC addresses whether axillary treatment can be de-escalated, post-surgery, in T1-3N1M0 breast cancer patients who have no residual nodal disease post-NACT. Methods: Design: ATNEC is a phase III, randomized (1:1), multi-centre trial, with embedded economic evaluation. Patients with proven axillary node metastases on needle biopsy receive NACT followed by sentinel node biopsy (SNB). If the sentinel nodes have converted to ypN0, ATNEC randomizes patients to axillary treatment (nodal radiotherapy [ART] or axillary nodal clearance [ANC]) vs. no further axillary treatment. Stratification: Institution, type of surgery (breast conserving surgery vs mastectomy), receptor status (triple negative vs HER2 positive vs ER positive and/or PR positive and HER2 negative). Inclusion criteria: • Age ≥ 18 • Male or female • T1-3N1M0 breast cancer at diagnosis (pre-NACT) • FNA or core biopsy confirmed axillary nodal metastases at presentation • ER and HER2 status evaluated on primary tumour • Received standard NACT as per local guidelines • Imaging of the axilla to assess response to NACT • Dual tracer SNB post-NACT and at least 3 nodes removed (sentinel nodes and marked node). o If a single tracer is used, the patient is eligible if the involved node is marked pre-NACT and at least 3 nodes removed (including the marked node) o If axillary node sampling is performed following failed localization of sentinel nodes, patient is eligible if at least 3 nodes removed (including the marked node). o If node is not marked, or marked node is not removed, patient is eligible if the histology report shows evidence of down-staging with complete pathological response in at least one node of the 3 removed nodes. • No evidence of nodal metastases post-NACT (ypN0) Exclusion criteria: • Bilateral invasive breast cancer • SNB prior to NACT • Previous ipsilateral axillary nodal surgery • Previous cancer within last 5 years or concomitant malignancy Aims: To assess whether omitting further axillary treatment (ART or ANC) for patients with early stage breast cancer and axillary nodal metastases on needle biopsy - who post NACT have no residual nodal disease on SNB (ypN0) - is non-inferior to axillary treatment in terms of disease-free survival, and whether lymphoedema is reduced at 5 years. Statistical methods: All analyses will be carried out on an intention-to-treat basis to preserve randomization, avoid bias from exclusions and preserve statistical power. Radiotherapy Quality Assurance: ATNEC has in-built radiotherapy QA coordinated by National Radiotherapy Trials QA (RTTQA) group. The RTQA monitors trial protocol compliance ensuring clinical outcomes reflect differences in randomization schedules rather than departures from the protocol. ATNEC is the only trial in the UK that offers QA for IMC radiotherapy. Screening Data: ATNEC collects screening data to monitor acceptance rates and reasons why patients decline the trial to identify ways to improve recruitment. Screening data until 30-Jun-22 shows that 69% of eligible patients were approached (244/354) and, of those approached, 45% were consented (109/244). For the 81 patients who declined, the most common reasons were; preference for axillary treatment (31%), preference for no axillary treatment (10%), no reason documented (23%) and ineligibility (21%). ClinicalTrials.gov: NCT04109079 Target accrual: 1900 Target sites: 100 Trial Status: Recruiting. As of 30-Jun-22: 52 sites open, 158 patients enrolled, 54 randomised. ATNEC is open to new sites and international collaboration. Citation Format: Amit Goyal, Sophie Nicholls, Andrea Marshall, Natalie Hammonds, Duncan Wheatley, Beatrix Elsberger, Janice Rose, Helen-Teresa Edwards, Roeum Butt, Abeer Shaaban, Shama Puri, Samreen Ahmed, Tara Homer, Luke Vale, Julie Bruce, Sophie J. Gasson, Helen Higgins, Janet A. Dunn. ATNEC: A multicentre, randomized trial investigating whether axillary treatment can be avoided in T1-3N1M0 breast cancer patients with no residual cancer in the axillary lymph nodes after neoadjuvant chemotherapy [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr OT1-09-02.

Ice accretion on component surfaces often causes severe impacts or accidents. Liquid-infused surfaces (LIS) have drawn much attention as icephobic materials for ice mitigation in recent years due to their outstanding icephobicity. However, the durability of LIS constructions remains a big challenge, including mechanical vulnerability and rapid depletion of lubricants. The practical applications of LIS materials are significantly restrained, and the full potential of LIS for ice prevention has yet to be demonstrated.A universal approach was proposed to introduce microporous metallic scaffolds in the LIS construction to increase the applicability and durability, and to prompt the potential of LIS for ice mitigation. Microporous Ni scaffolds were chosen to integrate with polydimethylsiloxane modified by silicone oil addition.The new LIS construction demonstrated significantly improved durability in icing/de-icing cyclic test, and it also offered a solution for the rapid oil depletion by restraining the deformation of the matrix material. Low ice adhesion strength could be maintained via a micro-crack initiation mechanism. The results indicated that the multi-phase LIS construction consisting of microporous Ni scaffolds effectively addressed the shackles of the icephobicity deterioration of LIS materials, confirming a new design strategy for the RD of icephobic surfaces.

Introduction: Undocumented immigrants are excluded from benefits that help compensate for scheduled outpatient hemodialysis (HD), compelling them to use emergency departments (ED) for HD. Consequently, these patients can receive “emergency-only” HD after presenting to the ED with critical illness due to untimely dialysis. Our objective was to describe the impact of emergency-only HD on hospital cost and resource utilization in a large academic health system that includes public and private hospitals. Methods: This retrospective observational study of health and accounting records took place at five teaching hospitals (one public, four private) over 24 consecutive months from January 2019 to December 2020. All patients had emergency and/or observation visits, renal failure codes (International Classification of Diseases, 10th Rev, Clinical Modification), emergency HD procedure codes, and an insurance status of “self-pay.” Primary outcomes included frequency of visits, total cost, and length of stay (LOS) in the observation unit. Secondary objectives included evaluating the variation in resource use between persons and comparing these metrics between the private and public hospitals. Results: A total of 15,682 emergency-only HD visits were made by 214 unique persons, for an average of 36.6 visits per person per year. The average cost per visit was $1,363, for an annual total cost of $10.7 million. The average LOS was 11.4 hours. This resulted in 89,027 observation-hours annually, or 3,709 observation-days. The public hospital dialyzed more patients compared to the private hospitals, especially due to repeat visits by the same persons. Conclusion: Health policies that limit hemodialysis of uninsured patients to the ED are associated with high healthcare costs and a misuse of limited ED and hospital resources.

Purpose This paper aims to consider stalking as an offending behaviour and the prevailing narratives associated with this offending behaviour given the increased attention of society and criminal justice. The stereotypes and labels associated with the offending behaviour often sensationalise aspects of those who engage in stalking. Frequently, individuals are portrayed as disturbed, psychopathic, mentally ill, violent and culturally deviant. Sometimes stalking behaviour is perversely downplayed as romantic perseverance. The impact of the stalker label extends outward from the act of marking legal and societal transgression, which impacts upon prospects for rehabilitation and desistance through the shaping of assumptions and maintenance of disempowering connotations. Design/methodology/approach This paper considers the impact of the stalking label as a therapeutic-, and perhaps rehabilitation-interfering problem for those who have stalked, drawing on recent research by Wheatley, Winder and Kuss (2020a). Findings It discusses the wide-ranging implications of labelling in this context and considers therapeutic approaches for intervention that may encourage rehabilitation engagement, mitigate shame and support desistance from a strengths-based perspective. Originality/value This paper draws on recent research exploring stalking case narratives of their own experiences of what drives stalking behaviour, existing labelling literature, and on specialist practitioners’ experiences of working with this group, to influence future thinking and research to address nuances highlighted.

Purpose This paper aims to present issues of deterrence related to stalking. Design/methodology/approach The authors have combined recent mixed method research findings and existing general deterrence literature with their practitioner experiences of working with this population, to provide a novel viewpoint paper intending to influence advancements in knowledge in this area. Findings Recent qualitative research investigating the function of stalking in a small sample (see Wheatley et al., 2020a) noted the participants’ focus on the lack of deterrence. For example, participants described feeling emotionally stuck in their pursuits, experiencing poor access to help and support, being ignorant of the potential custodial consequences of their offending and even stating that imprisonment provided a harsh yet necessary moment of reality. Originality/value This novel discussion paper reviews these findings in relation to both the available research based on deterrence generally and deterrence related to stalking and the experience of working with stalking cases in clinical practice. This paper explores what we know about the motivations that underlie stalking behaviour and how that relates to the effectiveness of deterrence, including the role of traditional criminal justice approaches to this type of offending.

Purpose This discussion paper aims to further explore narcissistic vulnerability as a psychological concept in relation to stalking, adding to the literature base by resurrecting this focus and exploring practical implications of this association through proposing a schema therapy (ST) approach. Design/methodology/approach Stalking results from an interaction of circumstances and a vulnerable personality. Understanding the psychology of those who stalk, before and during stalking episodes, is pivotal in helping the person stalking to desist and thus protect victims. Knowing how to most effectively intervene at the earliest opportunity with those stalking is an area receiving renewed attention. Not least due to the improved identification of stalking, but also the continued absence of empirical evidence on effective intervention approaches. This paper sets out to explore the utility of ST with stalking cases. Findings Recent research undertaken by Wheatley et al. (2020) with men who had stalked and were detained in prison within the UK highlighted narcissistic vulnerability as a key feature in their personalities. The original study provided support for the linked conceptualisations of narcissistic vulnerability, preoccupied attachment styles and the phenomenon of stalking. This paper extended discussions to explore the utility of ST to address narcissistic vulnerability in stalking cases. Originality/value This is an original discussion paper combining research with stalking cases, practitioner specialism, psychological theory and existing empirical literature to argue for the value of ST for addressing stalking.

Purpose There is an absence of qualitative research with individuals who have stalked. This special issue of articles draws on one study, rich with the meaning-making of experts by experience. That is, people who have stalked, been convicted and detained in UK prisons. The purpose of this issue is to provide forensic practitioners with an overview of current considerations for intervening with individuals who stalk. It does this by drawing together empirically derived interpreted experiences of men who stalk, expanding key discussions with expert practitioners in the field, working with those who stalk. It highlights current thinking on the psychology of stalking and multidisciplinary options for risk management. Furthermore, it provides an overview of necessary future directions. Design/methodology/approach Research findings from a recent, novel, mixed methods study (Wheatley, 2019 and Wheatleya et al., 2020) are discussed with other experienced stalking practitioners in the UK for reflection and discussion. The papers synthesise the research findings, existing psychological literature and practitioner experience to discuss implications for psychological practice with those who stalk. Findings The key findings resonated with current practitioners, providing a springboard for expanding thinking around stalking and crucial themes such as narcissistic vulnerability, deterrence, labelling and developing alternative meaningful activities. Research limitations/implications In providing this marriage of experiential expert insights, this Special Issue advances the practice of psychology in relation to those who stalk, having clear applications to the processes of risk assessment, intervention and management. Pivotally, how to enhance engagement opportunities to develop working and therapeutic relationships. Originality/value This issue introduces new subtopics, some of which have never been written about before. It provides discussion papers marrying research with practitioner experience, with a focus on practical applications within criminal psychology and future directions.

This article posits border abolition as a radical alternative to the Anthropocene. It convenes a group of eleven activists, organizers, scholars, practitioners, educators, and storytellers to discuss their work building cross-border solidarities along the US-Mexico border and in US immigration detention, Puerto Rico, Ghana, and the Bengal Delta. Participants provide critical analysis of the origins of environmental injustice and border violence and discuss how a confluence of ecological crisis, environmental racism, and border militarization since the 1980s disproportionately impacts BIPOC and queer/trans communities and exacerbates migrant precarity and displacement worldwide. Participants share ways they have built alternatives to border and ecological violence through migrant accompaniment, legal and policy advocacy, divestment activism, storytelling, education, and sustainability projects. The discussion is organized around three key themes: environmental injustice, racism, and borders; strategies adopted by organizers to build environmental and migrant justice; and visions of border abolition.

Thymic stromal lymphopoietin (TSLP) has been shown to play a central role in the initiation and persistence of allergic responses.We evaluated whether tezepelumab, a human monoclonal anti-TSLP antibody, improved the efficacy of subcutaneous allergen immunotherapy (SCIT) and promoted the development of tolerance in patients with allergic rhinitis.We conducted a double-blind parallel design trial in patients with cat allergy. A total of 121 patients were randomized to receive either intravenous tezepelumab plus subcutaneous cat SCIT, cat SCIT alone, tezepelumab alone, or placebo for 52 weeks, followed by 52 weeks of observation. Nasal allergen challenge (NAC), skin testing, and blood and nasal samples were obtained throughout the study.At week 52, the NAC-induced total nasal symptom scores (TNSS) (calculated as area under the curve [AUCInhibition of TSLP augments the efficacy of SCIT during therapy and may promote tolerance after a 1-year course of treatment. (ClinicalTrials.gov NCT02237196).

Small cell lung cancer (SCLC) is an aggressive neuroendocrine tumour with metastatic propensity. Stereotactic body radiation therapy (SBRT) is an emerging therapeutic option for SCLC, despite limited supporting evidence. By evaluating the use of SBRT in very limited stage (VLS) SCLC at our institution, we aimed to contribute to the existing knowledge in this area while establishing a basis for further research. We performed a retrospective review of all cases of VLS-SCLC treated with SBRT between 2013 and 2020. Baseline demographics, diagnostic, and treatment information were collected. The primary outcome was overall survival (OS). We identified 46 patients with pathologically confirmed VLS-SCLC; 25 were treated with SBRT, and the remainder received either surgery, conventional radiation therapy, chemotherapy, or palliative-intent therapy. After a median follow-up of 23.7 months, 44% of the patients had died; the median OS was of 24.4 months for the SBRT cohort and 67.0 months for the curative intent non-SBRT cohort. The difference in disease recurrence and survival between cohorts was underpowered and not statistically significant. Higher baseline ECOG and comorbidity was noted in the SBRT cohort.

Paclitaxel is commonly used as first-line chemotherapy for HER2-negative metastatic breast cancer (MBC) patients. However, with response rates of 21.5-53.7% and significant risk of peripheral neuropathy, there is need for better chemotherapy.This open-label phase II/III trial randomised HER2-negative MBC patients 1:1 to either 6 cycles of three-weekly cabazitaxel (25 mg/m158 patients were recruited. Comparing cabazitaxel to paclitaxel, median PFS was 6.7 vs 5.8 months (HR 0.87; 80%CI 0.70-1.08, P = 0.4). There was no difference in median OS (20.6 vs 18.2 months, HR 1.00; 95%CI 0.69-1.45, P = 0.99), ORR (41.8% vs 36.7%) or TTR (HR 1.09; 95%CI 0.68-1.75, P = 0.7). Grade ≥3 adverse events occurred in 41.8% on cabazitaxel and 46.8% on paclitaxel; the most common being neutropenia (16.5%) and febrile neutropenia (12.7%) cabazitaxel and neutropenia (8.9%) and lung infection (7.6%) paclitaxel. Peripheral neuropathy of any grade occurred in 54.5% paclitaxel vs 16.5% cabazitaxel. Mean EQ-5D-5L single index utility score (+0.05; 95%CI 0.004-0.09, P = 0.03) and visual analogue scale score (+7.7; 95%CI 3.1-12.3, P = 0.001) were higher in cabazitaxel vs paclitaxel.Three-weekly cabazitaxel in HER2-negative MBC does not significantly improve PFS compared to weekly paclitaxel, although it has a lower risk of peripheral neuropathy with better patient reported QoL outcomes. It is well tolerated and requires fewer hospital visits.

Management of the anterior component of unstable lateral compression (LC) pelvic ring injuries remains controversial. Common internal fixation options include plating and superior pubic ramus screws. These constructs have been evaluated in anterior-posterior compression (APC) fracture patterns, but no study has compared the two for unstable LC patterns, which is the purpose of this study.A rotationally unstable LC pelvic ring injury was modeled in 10 fresh frozen cadaver specimens by creating a complete sacral fracture, disruption of posterior ligaments, and ipsilateral superior and inferior rami osteotomies. All specimens were repaired posteriorly with two fully threaded 7 mm cannulated transiliac-transsacral screws through the S1 and S2 corridors. The superior ramus was repaired with either a 3.5 mm pelvic reconstruction plate (n = 5) or a bicortical 5.5 mm cannulated retrograde superior ramus screw (n = 5). Specimens were loaded axially in single leg support for 1000 cycles at 400 N followed by an additional 3 cycles at 800 N. Displacement and angulation of the superior and inferior rami osteotomies were measured with a three-dimensional (3D) motion tracker. The two fixation methods were then compared with Mann-Whitney U-Tests.Retrograde superior ramus screw fixation had lower average displacement and angulation than plate fixation in all categories, with the motion at the inferior ramus at 800 N of loading showing a statistically significant difference in angulation.Although management of the anterior ring in unstable LC injuries remains controversial, indications for fixation are becoming more defined over time. In this study, the 5.5 mm cannulated retrograde superior ramus screw significantly outperformed the 3.5 mm reconstruction plate in angulation of the inferior ramus fracture at 800 N. No other significance was found, however the ramus screw demonstrated lower average displacements and angulations in all categories for both the inferior and superior ramus fractures.

We present new optical transmission spectra for two hot Jupiters: WASP-25b (M~=~0.56~M$_J$; R~=~1.23~R$_J$; P~=~3.76~days) and WASP-124b (M~=~0.58~M$_J$; R~=~1.34~R$_J$; P~=~3.37~days), with wavelength coverage of 4200 -- 9100\AA~and 4570 -- 9940\AA, respectively. These spectra are from EFOSC2 mounted on the New Technology Telescope (NTT) and IMACS on Magellan Baade. No strong spectral features were found at 4 and 6 scale heights, respectively. \texttt{Exoretrievals} and \texttt{PLATON} retrievals moderately favor ($\sim 3 \sigma$) stellar activity for WASP-25b, while a completely featureless spectrum is slightly favored ( < 2 $\sigma$) for WASP-124b. For both planets the retrievals found a wide range in the depth where the atmosphere is optically thick ($\sim$0.4 $\mu$bars -- 6 bars), and recover a temperature that is consistent with the planets' equilibrium temperatures, but with wide uncertainties (up to $\pm$400K). For WASP-25b, the models also favor stellar spots that are $\sim$1400--1800K cooler than the surrounding photosphere. The fairly weak constraints on parameters owe to the relatively low precision of the data, with an average precision of 840 and 1300~ppm per bin for WASP-25 and WASP-124b, respectively. The average width of each bin is $\sim$ 150{\AA} and 160 {\AA}, respectively. However, some contribution might still be due to an inherent absence of absorption or scattering in the planets' upper atmospheres, possibly because of aerosols. We attempt to fit the strength of the sodium signals to the aerosol--metallicity trend proposed by \cite{McGruder:2023}, and find WASP-25b is consistent with the prediction, while WASP-124b has too large uncertainties to better constrain the predicted trend., The binned light curves for each transit (Figures 6 - 11). Including the unused partial transit of WASP-124 on UT190615. The individual transmission spectra of each night, including the unused partial transit of WASP-124. In addition, the combined transmission spectra (Table 6).

Diabetes has been recognised as a major risk factor for COVID-19 mortality and hospital complications in earlier studies.To examine the characteristics of hospitalised COVID-19 patients with diabetes and the impact of diabetes and hyperglycaemia on hospital outcomes.This was a retrospective cohort study. Admission glucose levels, HbA1c, diabetes status and hospital outcomes were determined for subjects admitted from June to November 2021 by matching a pathology data set, a clinical data set and the hospital administrative database. The outcomes of interest were death, intensive care unit (ICU) admission and length of stay (LOS).There were 1515 individuals admitted with COVID-19 with 49 deaths (3.2%) and 205 (13.5%) ICU admissions. The median length of hospital stay was 3.7 days. Three hundred and ten patients (20%) had diabetes, with 46 (15%) newly diagnosed. Patients with diabetes had a higher mortality than patients who did not have diabetes (8% vs 2%, P 0.001), were more likely to be admitted to ICU (20% vs 12%, P = 0.001) and have longer median LOS stay (6.6 (interquartile range (IQR) 2.9-12.5) vs 2.9 (IQR 0.5-7.1) days, P 0.001). In multivariate models, neither diabetes nor admission glucose predicted death. Admission glucose level but not diabetes was an independent predictor of ICU admission and LOS.There is a high prevalence of diabetes among patients hospitalised with COVID-19, with worse outcomes. In contrast to previous studies, the association of diabetes with mortality was not significant when adjusted for other variables. This is possibly related to the benefits of vaccination and current medical and ICU interventions.

Patients undergoing cardiac surgery are at significant risk of developing postoperative acute kidney injury (AKI). Neutrophil-lymphocyte ratio (NLR) is a widely available inflammatory biomarker which may be of prognostic value in this setting.We conducted a systematic review and meta-analysis of studies reporting associations between perioperative NLR with postoperative AKI. We searched Medline, Embase and the Cochrane Library, without language restriction, from inception to May 2022 for relevant studies. We meta-analysed the reported odds ratios (ORs) with 95% confidence intervals (CIs) for both elevated preoperative and postoperative NLR with risk of postoperative AKI and need for renal replacement therapy (RRT). We conducted a meta-regression to explore inter-study statistical heterogeneity.Twelve studies involving 10,724 participants undergoing cardiac surgery were included, with eight studies being deemed at high risk of bias using PROBAST modelling. We found statistically significant associations between elevated preoperative NLR and postoperative AKI (OR 1.45, 95% CI 1.18-1.77), as well as postoperative need for RRT (OR 2.37, 95% CI 1.50-3.72). Postoperative NLR measurements were not of prognostic significance.Elevated preoperative NLR is a reliable inflammatory biomarker for predicting AKI following cardiac surgery.

Saleyard Bridge carries the A465 Heads of the Valleys Road over the River Clydach near Gilwern, Monmouthshire, UK. It comprises a 67 m single-span steel–concrete composite multi-girder superstructure made integral with the abutments. A full-depth precast deck was chosen to tackle site constraints and improve constructability. The alternative precast panel connection detail developed used straight laps to overcome the problems that can arise from using typical U-bar loop type connections between precast deck panels. The successful use of the precast panels proved that a deck design with straight laps was a practical alternative. The ability to increase the multi-beam centres and avoid cantilever edge formwork created a more economical solution with savings estimated at £500 000. The paper examines the detailed design and construction planning needed to realise the savings and speed up construction as well as improving site safety. The lessons learnt are also applicable to the wider use of precast panels as an alternative to in situ concreting.

Hiroshi Nishimune,1,2 Kimberly G Stanford,3 Jie Chen,1 James D Odum,3 Alexander D Rorie,3 Robert S Rogers,4 Joshua L Wheatley,3 Paige C Geiger,3 John A Stanford3 1Department of Anatomy and Cell Biology, University of Kansas Medical Center, Kansas City, KS, USA; 2Tokyo Metropolitan Institute of Gerontology, Neurobiology of Aging, Tokyo, Japan; 3Department of Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City, KS, USA; 4Departments of Physiology and Basic Sciences, Kansas City University of Medicine and Biosciences, Joplin, MO, USACorrespondence: John A Stanford, Department of Molecular & Integrative Physiology, University of Kansas Medical Center, 3901 Rainbow Blvd., MS 3051, Kansas City, KS, 66160, USA, Tel +913-588-7416, Fax +913-588-5677, Email jstanford@kumc.eduIntroduction: The symptoms of Amyotrophic Lateral Sclerosis (ALS) include muscle weakness and eventual paralysis. These symptoms result from denervation of the neuromuscular junction (NMJ) and motor neuron cell death in the brain and spinal cord. Due to the “dying back” pattern of motor neuron degeneration, protecting NMJs should be a therapeutic priority. Although exercise has the potential to protect against NMJ denervation, its use in ALS has been controversial. Most preclinical studies have focused on aerobic exercise, which report that exercise can be beneficial at moderate intensities. The effects of resistance exercise on NMJ preservation in limb muscles have not been explored.Methods: We trained male SOD1-G93A rats, which model ALS, to perform a unilateral isometric forelimb resistance exercise task. This task allows within-animal comparisons of trained and untrained forelimbs. We then determined the effects of isometric resistance exercise on NMJ denervation and AMP kinase (AMPK) activation in forelimb muscles.Results: Our results revealed that SOD1-G93A rats were able to learn and perform the task similarly to wildtype rats, even after loss of body weight. SOD1-G93A rats exhibited significantly greater NMJ innervation in their trained vs their untrained forelimb biceps muscles. Measures of activated (phosphorylated) AMPK (pAMPK) were also greater in the trained vs untrained forelimb triceps muscles.Discussion: These results demonstrate that isometric resistance exercise may protect against NMJ denervation in ALS. Future studies are required to determine the extent to which our findings generalize to female SOD1-G93A rats and to other subtypes of ALS.Keywords: strength training, resistance, isometric, neuromuscular

Site-selective installation of C–Me bonds remains a powerful and sought-after tool to alter the chemical and pharmacological properties of a molecule. Direct C–H functionalization provides an attractive means of achieving this transformation. Such protocols, however, typically utilize harsh conditions and hazardous methylating agents with poor applicability towards late-stage functionalization. Furthermore, highly mono-selective methylation protocols remain scarce. Herein, we report an efficient mono-selective, directed ortho-methylation of arenes using N,N,N-trimethylanilinium salts as a non-carcinogenic, bench-stable methylating agents. We extend this protocol to d3-methylation, in addition to the late-stage functionalization of pharmaceutically active compounds. Detailed kinetic studies indicate the rate-limiting insitu formation of MeI as integral to the observed reactivity.