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The transport sector’s share of Kenya’s total greenhouse gas (GHG) emissions has been projected to grow from 11% in 2015 to 14.7% by 2030 in a business as usual (BAU) scenario [1]. In line with the Kenyan Government’s goal of reducing total GHG emissions by 32% relative to BAU in 2030 [2], it has begun several initiatives to start mitigating its transport emissions, including opportunities related to growing its nascent e-mobility sector. The private sector, with a range of around 25 new e-mobility companies [3], has been providing solutions through the supply of various electric vehicles aimed at serving the local market, while also leading the way in deploying charging and battery swapping infrastructure.

The Modular Multilevel Converter (MMC) has become the leading technology for delivering High Voltage DC (HVDC) power transmission, due to its scalability, harmonic quality and ability to ride through AC network faults. However, unbalanced AC-Grid conditions create harmonics at twice the fundamental AC-Grid frequency that can propagate to the DC-side as a result of the unbalance in the arm energy. These harmonics may risk excitation of network resonances as well as the maloperation of connected assets, and thus control action is needed to suppress such harmonics. Several different control solutions have been proposed in the literature and the aim of this paper is to provide a comparison of the performance of a sample of these techniques on a 1.2 kV/12 kVA lab-scale MMC demonstrator and cable emulator under unbalanced AC-Grid conditions. The sample of control methods chosen showcases a range of design complexity from basic direct modulation techniques with no DC current control to advanced energy based controllers. Experimental testing of these controllers under the same test condition not only validates the operation of each individual controller but also allows like-for-like comparison of their relative performance. It was found that the controllers tested were capable of significantly suppressing double line-frequency components on the DC -bus compared to the base case, however the more complex controllers had the additional benefit of being able to tune the transient response.

Using spin-echo Nuclear Magnetic Resonance in the model Transverse-Field Ising system TmVO$_4$, we show that low frequency quantum fluctuations at the quantum critical point have a very different effect on $^{51}$V nuclear-spins than classical low-frequency noise or fluctuations that arise at a finite temperature critical point. Spin-echos filter out the low frequency classical noise but not the quantum fluctuations. This allows us to directly visualize the quantum critical fan and demonstrate the persistence of quantum fluctuations at the critical coupling strength in TmVO$_4$ to high temperatures in an experiment that remains transparent to finite temperature classical phase transitions. These results show that while dynamical decoupling schemes can be quite effective in eliminating classical noise in a qubit, a quantum critical environment may lead to rapid entanglement and decoherence., Comment: 10 pages, 5 figures

The increasing integration of inverter-based renewable generation into the network as Grid-Following inverters (GFL), combined with the reduction in traditional Synchronous Generation (SG) leads to a reduction in inertia and to instabilities. To alleviate this, researchers have proposed using a mix of GFL and Grid-Forming controllers (GFM). However, there is a lack of simple system-wide analytical models. This paper proposes a swing equation to describe the transient frequency response of GFL that has droop regulation of real and reactive power. The swing equation for GFL with droop has an inertia and a damping term as do SG and GFM swing equations. Simulations show that the use of swing equations for GFM and GFL is accurate to study the transient frequency stability following a loss of infeed. GFM and GFL damping are equivalent, and their sum allows prediction of frequency deviation. However, although SG and GFM inertia terms limit the initial Rate of Change of Frequency (RoCoF), the GFL inertia term is found not to contribute towards limitation of the initial RoCoF. Instead, the GFL RoCoF is seen to follow adjacent GFM RoCoF and worsens slightly when the GFL Phase Locked Loop (PLL) bandwidth is reduced.

The ELOSPHERES project is a collaboration between researchers at Imperial College London and University College London which aims to improve the efficacy of hearing aids. The benefit obtained from hearing aids varies significantly between listeners and listening environments. The noisy, reverberant environments which most people find challenging bear little resemblance to the clinics in which consultations occur. In order to make progress in speech enhancement, algorithms need to be evaluated under realistic listening conditions. A key aim of ELOSPHERES is to create a virtual reality-based test environment in which alternative speech enhancement algorithms can be evaluated using a listener-in-the-loop paradigm. In this paper we present the sap-elospheres-audiovisual-test (SEAT) platform and report the results of an initial experiment in which it was used to measure the benefit of visual cues in a speech intelligibility in spatial noise task.

Background: Sudden smell loss is a specific early symptom of COVID-19, which, prior to the emergence of Omicron, had estimated prevalence of ~40% to 75%. Chemosensory impairments affect physical and mental health, and dietary behavior. Thus, it is critical to understand the rate and time course of smell recovery. The aim of this cohort study was to characterize smell function and recovery up to 11 months post COVID-19 infection. Methods: This longitudinal survey of individuals suffering COVID-19-related smell loss assessed disease symptoms and gustatory and olfactory function. Participants (n=12,313) who completed an initial survey (S1) about respiratory symptoms, chemosensory function and COVID-19 diagnosis between April and September 2020, were invited to complete a follow-up survey (S2). Between September 2020 and February 2021, 27.5% participants responded (n=3,386), with 1,468 being diagnosed with COVID-19 and suffering co-occurring smell and taste loss at the beginning of their illness. Results: At follow-up (median time since COVID-19 onset ~200 days), ~60% of women and ~48% of men reported less than 80% of their pre-illness smell ability. Taste typically recovered faster than smell, and taste loss rarely persisted if smell recovered. Prevalence of parosmia and phantosmia was ~10% of participants in S1 and increased substantially in S2: ~47% for parosmia and ~25% for phantosmia. Persistent smell impairment was associated with more symptoms overall, suggesting it may be a key marker of long-COVID illness. The ability to smell during COVID-19 was rated slightly lower by those who did not eventually recover their pre-illness ability to smell at S2. Conclusions: While smell ability improves for many individuals who lost it during acute COVID-19, the prevalence of parosmia and phantosmia increases substantially over time. Olfactory dysfunction is associated with broader persistent symptoms of COVID-19, and may last for many months following acute COVID-19. Taste loss in the absence of smell loss is rare. Persistent qualitative smell symptoms are emerging as common long-term sequelae; more research into treatment options is strongly warranted given that even conservative estimates suggest millions of individuals may experience parosmia following COVID-19. Healthcare providers worldwide need to be prepared to treat post COVID-19 secondary effects on physical and mental health. Trial registration: This project was pre-registered at OSF 1.

For more than half a century, researchers around the world have been engaged in attempts to achieve fusion ignition as a proof of principle of various fusion concepts. Following the Lawson criterion, an ignited plasma is one where the fusion heating power is high enough to overcome all the physical processes that cool the fusion plasma, creating a positive thermodynamic feedback loop with rapidly increasing temperature. In inertially confined fusion, ignition is a state where the fusion plasma can begin "burn propagation" into surrounding cold fuel, enabling the possibility of high energy gain. While "scientific breakeven" (i.e., unity target gain) has not yet been achieved (here target gain is 0.72, 1.37 MJ of fusion for 1.92 MJ of laser energy), this Letter reports the first controlled fusion experiment, using laser indirect drive, on the National Ignition Facility to produce capsule gain (here 5.8) and reach ignition by nine different formulations of the Lawson criterion.

Background: Sudden smell loss is a specific early symptom of COVID-19, which, prior to the emergence of Omicron, had estimated prevalence of ~40% to 75%. Chemosensory impairments affect physical and mental health, and dietary behavior. Thus, it is critical to understand the rate and time course of smell recovery. The aim of this cohort study was to characterize smell function and recovery up to 11 months post COVID-19 infection. Methods: This longitudinal survey of individuals suffering COVID-19-related smell loss assessed disease symptoms and gustatory and olfactory function. Participants (n=12,313) who completed an initial survey (S1) about respiratory symptoms, chemosensory function and COVID-19 diagnosis between April and September 2020, were invited to complete a follow-up survey (S2). Between September 2020 and February 2021, 27.5% participants responded (n=3,386), with 1,468 being diagnosed with COVID-19 and suffering co-occurring smell and taste loss at the beginning of their illness. Results: At follow-up (median time since COVID-19 onset ~200 days), ~60% of women and ~48% of men reported less than 80% of their pre-illness smell ability. Taste typically recovered faster than smell, and taste loss rarely persisted if smell recovered. Prevalence of parosmia and phantosmia was ~10% of participants in S1 and increased substantially in S2: ~47% for parosmia and ~25% for phantosmia. Persistent smell impairment was associated with more symptoms overall, suggesting it may be a key marker of long-COVID illness. The ability to smell during COVID-19 was rated slightly lower by those who did not eventually recover their pre-illness ability to smell at S2. Conclusions: While smell ability improves for many individuals who lost it during acute COVID-19, the prevalence of parosmia and phantosmia increases substantially over time. Olfactory dysfunction is associated with broader persistent symptoms of COVID-19, and may last for many months following acute COVID-19. Taste loss in the absence of smell loss is rare. Persistent qualitative smell symptoms are emerging as common long-term sequelae; more research into treatment options is strongly warranted given that even conservative estimates suggest millions of individuals may experience parosmia following COVID-19. Healthcare providers worldwide need to be prepared to treat post COVID-19 secondary effects on physical and mental health. Trial registration: This project was pre-registered at OSF 1.

Felicia Forma,1 Teresa Green,2 Seung Kim,2 Christie Teigland2 1Otsuka Pharmaceutical Development & Commercialization, Inc., Princeton, NJ, USA; 2Avalere Health — an Inovalon Company, Washington, DC, USACorrespondence: Christie Teigland Email cteigland@avalere.comObjective: To evaluate differences in patient characteristics and real-world outcomes in two distinct high-risk cohorts of patients with serious mental illness (SMI).Methods: Retrospective cross-sectional analysis using a national multi-payer claims database. Two SMI cohorts identified by a technical expert panel—patients recently discharged (RD) from an SMI-related hospitalization and early episode (EE) patients—were evaluated for antipsychotic medication adherence, healthcare utilization, and spending patterns.Results: The analysis included 51,705 patients with bipolar disorder, major depressive disorder, and schizophrenia. More than half were over age 46 and > 60% were female. Adherence to psychiatric medications was low (52.5% RD and 16.1% EE). More than half of RD and 100% of EE patients switched medications at least once annually, but 19% of RD patients switched ≥ 2 times compared to 14% of EE. The RD cohort (generally older and sicker) had higher psychiatric related utilization and higher annual costs (US$21,171 versus US$15,398). In both cohorts, women were more likely to have an emergency department (ED) and primary care provider (PCP) visit, but less likely to be hospitalized. Patients age < 46 were less likely to have a PCP visit and more likely to have an ED visit, but younger patients age 18– 24 were less likely to be hospitalized.Conclusion: Efforts to manage SMI are confounded by heterogeneity and low adherence to treatment. By better understanding which patients are at higher risk for specific adverse outcomes, clinicians can target interventions more appropriately to reduce the significant burden of SMI.Keywords: adherence, schizophrenia, major depressive disorder, bipolar disorder, healthcare utilization

This Briefing Paper explores the impact the COVID-19 pandemic had on the UK’s energy sector over the course of the first government-mandated national lockdown that began on 23 March 2020. Research from several aspects of the Integrated Development of Low-carbon Energy Systems (IDLES) programme at Imperial College London is presented in one overarching paper. The main aim is to determine what lessons can be learnt from that lockdown period, given the unique set of challenges it presented in our daily lives and the changes it brought about in energy demand, supply, and use. Valuable insights are gained into how working-from-home policies, electric vehicles, and low-carbon grids can be implemented, incentivised, and managed effectively.

Editorial

Background Chemotherapy improves outcomes for high risk early breast cancer (EBC) patients but is infrequently offered to older individuals. This study determined if there are fit older patients with high-risk disease who may benefit from chemotherapy. Methods A multicentre, prospective, observational study was performed to determine chemotherapy (±trastuzumab) usage and survival and quality-of-life outcomes in EBC patients aged ≥70 years. Propensity score-matching adjusted for variation in baseline age, fitness and tumour stage. Results Three thousands four hundred sixteen women were recruited from 56 UK centres between 2013 and 2018. Two thousands eight hundred eleven (82%) had surgery. 1520/2811 (54%) had high-risk EBC and 2059/2811 (73%) were fit. Chemotherapy was given to 306/1100 (27.8%) fit patients with high-risk EBC. Unmatched comparison of chemotherapy versus no chemotherapy demonstrated reduced metastatic recurrence risk in high-risk patients(hazard ratio [HR] 0.36 [95% CI 0.19–0.68]) and in 541 age, stage and fitness-matched patients(adjusted HR 0.43 [95% CI 0.20–0.92]) but no benefit to overall survival (OS) or breast cancer-specific survival (BCSS) in either group. Chemotherapy improved survival in women with oestrogen receptor (ER)-negative cancer (OS: HR 0.20 [95% CI 0.08–0.49];BCSS: HR 0.12 [95% CI 0.03–0.44]).Transient negative quality-of-life impacts were observed. Conclusions Chemotherapy was associated with reduced risk of metastatic recurrence, but survival benefits were only seen in patients with ER-negative cancer. Quality-of-life impacts were significant but transient. Trial Registration ISRCTN 46099296

Background\ud \ud Chemotherapy improves outcomes for high risk early breast cancer (EBC) patients but is infrequently offered to older individuals. This study determined if there are fit older patients with high-risk disease who may benefit from chemotherapy.\ud \ud \ud Methods\ud \ud A multicentre, prospective, observational study was performed to determine chemotherapy (±trastuzumab) usage and survival and quality-of-life outcomes in EBC patients aged ≥70 years. Propensity score-matching adjusted for variation in baseline age, fitness and tumour stage.\ud \ud \ud Results\ud \ud Three thousands four hundred sixteen women were recruited from 56 UK centres between 2013 and 2018. Two thousands eight hundred eleven (82%) had surgery. 1520/2811 (54%) had high-risk EBC and 2059/2811 (73%) were fit. Chemotherapy was given to 306/1100 (27.8%) fit patients with high-risk EBC. Unmatched comparison of chemotherapy versus no chemotherapy demonstrated reduced metastatic recurrence risk in high-risk patients(hazard ratio [HR] 0.36 [95% CI 0.19–0.68]) and in 541 age, stage and fitness-matched patients(adjusted HR 0.43 [95% CI 0.20–0.92]) but no benefit to overall survival (OS) or breast cancer-specific survival (BCSS) in either group. Chemotherapy improved survival in women with oestrogen receptor (ER)-negative cancer (OS: HR 0.20 [95% CI 0.08–0.49];BCSS: HR 0.12 [95% CI 0.03–0.44]).Transient negative quality-of-life impacts were observed.\ud \ud \ud Conclusions\ud \ud Chemotherapy was associated with reduced risk of metastatic recurrence, but survival benefits were only seen in patients with ER-negative cancer. Quality-of-life impacts were significant but transient.\ud \ud \ud Trial Registration\ud \ud ISRCTN 46099296

Background\ud \ud Rates of surgery and adjuvant therapy for breast cancer vary widely between breast units. This may contribute to differences in survival. This cluster RCT evaluated the impact of decision support interventions (DESIs) for older women with breast cancer, to ascertain whether DESIs influenced quality of life, survival, decision quality, and treatment choice.\ud \ud \ud Methods\ud \ud A multicentre cluster RCT compared the use of two DESIs against usual care in treatment decision-making in older women (aged at least ≥70 years) with breast cancer. Each DESI comprised an online algorithm, booklet, and brief decision aid to inform choices between surgery plus adjuvant endocrine therapy versus primary endocrine therapy, and adjuvant chemotherapy versus no chemotherapy. The primary outcome was quality of life. Secondary outcomes included decision quality measures, survival, and treatment choice.\ud \ud \ud Results\ud \ud A total of 46 breast units were randomized (21 intervention, 25 usual care), recruiting 1339 women (670 intervention, 669 usual care). There was no significant difference in global quality of life at 6 months after the baseline assessment on intention-to-treat analysis (difference –0.20, 95 per cent confidence interval (C.I.) –2.69 to 2.29; P = 0.900). In women offered a choice of primary endocrine therapy versus surgery plus endocrine therapy, knowledge about treatments was greater in the intervention arm (94 versus 74 per cent; P = 0.003). Treatment choice was altered, with a primary endocrine therapy rate among women with oestrogen receptor-positive disease of 21.0 per cent in the intervention versus 15.4 per cent in usual-care sites (difference 5.5 (95 per cent C.I. 1.1 to 10.0) per cent; P = 0.029). The chemotherapy rate was 10.3 per cent at intervention versus 14.8 per cent at usual-care sites (difference –4.5 (C.I. –8.0 to 0) per cent; P = 0.013). Survival was similar in both arms.\ud \ud \ud Conclusion\ud \ud The use of DESIs in older women increases knowledge of breast cancer treatment options, facilitates shared decision-making, and alters treatment selection.\ud \ud \ud Trial registration numbers: EudraCT 2015-004220-61 (https://eudract.ema.europa.eu/), ISRCTN46099296 (http://www.controlled-trials.com).

Background Rates of surgery and adjuvant therapy for breast cancer vary widely between breast units. This may contribute to differences in survival. This cluster RCT evaluated the impact of decision support interventions (DESIs) for older women with breast cancer, to ascertain whether DESIs influenced quality of life, survival, decision quality, and treatment choice. Methods A multicentre cluster RCT compared the use of two DESIs against usual care in treatment decision-making in older women (aged at least ≥70 years) with breast cancer. Each DESI comprised an online algorithm, booklet, and brief decision aid to inform choices between surgery plus adjuvant endocrine therapy versus primary endocrine therapy, and adjuvant chemotherapy versus no chemotherapy. The primary outcome was quality of life. Secondary outcomes included decision quality measures, survival, and treatment choice. Results A total of 46 breast units were randomized (21 intervention, 25 usual care), recruiting 1339 women (670 intervention, 669 usual care). There was no significant difference in global quality of life at 6 months after the baseline assessment on intention-to-treat analysis (difference –0.20, 95 per cent confidence interval (C.I.) –2.69 to 2.29; P = 0.900). In women offered a choice of primary endocrine therapy versus surgery plus endocrine therapy, knowledge about treatments was greater in the intervention arm (94 versus 74 per cent; P = 0.003). Treatment choice was altered, with a primary endocrine therapy rate among women with oestrogen receptor-positive disease of 21.0 per cent in the intervention versus 15.4 per cent in usual-care sites (difference 5.5 (95 per cent C.I. 1.1 to 10.0) per cent; P = 0.029). The chemotherapy rate was 10.3 per cent at intervention versus 14.8 per cent at usual-care sites (difference –4.5 (C.I. –8.0 to 0) per cent; P = 0.013). Survival was similar in both arms. Conclusion The use of DESIs in older women increases knowledge of breast cancer treatment options, facilitates shared decision-making, and alters treatment selection. Trial registration numbers: EudraCT 2015-004220-61 (https://eudract.ema.europa.eu/), ISRCTN46099296 (http://www.controlled-trials.com).

Objective: We surveyed obstetric sonographers, who are at the forefront of the screening process to determine how barriers to prenatal cardiac screening impacted screening abilities. Methods: We performed a cross-sectional national survey of obstetric sonographers in the United States using a sampling frame from American Registry of Diagnostic Medical Sonography mailing lists. The web survey measured the ability to obtain and interpret fetal heart images. Several cognitive, sociodemographic, and system-level factors were measured, including intention to perform cardiac imaging. Regression and mediation analyses determined factors associated with intention to perform and ability to obtain and interpret cardiac images. Subgroup analyses of sonographers in tertiary versus nontertiary centers were also performed. Results: Survey response rate either due to noncontact or nonresponse was 40%. Of 480 eligible sonographers, ~30% practiced in tertiary settings. Sonographers had lower intention to perform outflow views compared to 4 chambers. Higher self-efficacy and professional expectations predicted higher odds of intention to perform outflow views (OR 2.8, 95% CI 1.9–4.2 and 1.9, 95% CI 1.1–3.0, respectively). Overall accuracy of image interpretation was 65% (±14%). For the overall cohort and nontertiary subgroup, higher intention to perform outflows was associated with increased accuracy in overall image interpretation. For the tertiary subgroup, self-efficacy and feedback were strongly associated with accuracy. Conclusions: We identified several modifiable (some heretofore unrecognized) targets to improve prenatal cardiac screening. Priorities identified by sonographers that are associated with screening success should guide future interventions.

Due to their tuneable band gaps, ease of processing and excellent optoelectronic properties, perovskite-based solar cells have attracted much attention in recent years, with rapidly increasing efficiencies which already match those of the industrially dominant multi-crystalline silicon. This work concerns modification of the perovskite semiconductor layer in low band gap materials containing the mixed metals tin and lead. These materials have promising commercial applications both in theoretically optimal single-junction solar cells and in multi-junction perovskite-perovskite tandem devices as a replacement for silicon. An improved processing method by modification of the deposition solvent together with an appropriate antisolvent or stream of nitrogen is shown to slow crystallisation, leading to thin films with long diffusion length and high mobility. Use of a formamidinium cation rather than methylammonium is shown to improve efficiency, with further performance enhancement on substitution of a small amount of caesium. An optoelectronically defective region is identified with small amounts of substitution of lead for tin, with a recovery in film quality and lowest band gap values with 40-60% tin content. In collaboration with others, this processing enhancement leads to high efficiency single-junction low band gap perovskite solar cells and multi-junction perovskite- perovskite tandem devices. The additives tin(II) fluoride and tin(II) chloride are shown to function as reducing agents in precursor solutions, and compensators in thin films for tin vacancies produced by the instability of tin(II). These additives are able to rebalance the stoichiometry of both tin(II) and iodide, allowing formation of perovskite films with less bulk vacancy defects, leading to improved morphology and optoelectronic quality, and less initial p-doping. A secondary phase seen on the surface of the films is identified as excess tin(II) fluoride. Over time in air, competing p-doping and degradation mechanisms are identified, and additives shown to slow the onset of degradation. High efficiency solar cells are fabricated with both additives, with tin(II) fluoride showing less sensitivity to precise processing concentration. A compositional screening study of methylammonium, formamidinium and caesium cations in low band gap perovskite materials is performed, identifying thin film properties and fabricating solar cells from compositions with different combinations of these cations using a universal deposition protocol. The resulting compositional space is demonstrated to be almost fully accessible using this method, with all three cations substituting into the perovskite crystal lattice, although a compositional instability between formamidinium and caesium is identified. Power is generated from solar cells of all other compositions, laying the foundations for future optimisation work on new low band gap materials within this compositional space.

Background\ud \ud In the UK there is variation in the treatment of older women with breast cancer, with up to 40% receiving primary endocrine therapy (PET), which is associated with inferior survival. Case mix and patient choice may explain some variation in practice but clinician preference may also be important.\ud \ud \ud \ud Methods\ud \ud A multicentre prospective cohort study of women aged >70 with operable breast cancer. Patient characteristics (health status, age, tumour characteristics, treatment allocation and decision-making preference) were analysed to identify whether treatment variation persisted following case-mix adjustment. Expected case-mix adjusted surgery rates were derived by logistic regression using the variables age, co-morbidity, tumour stage and grade. Concordance between patients’ preferred and actual decision-making style was assessed and associations between age, treatment and decision-making style calculated.\ud \ud \ud \ud Results\ud \ud Women (median age 77, range 70–102) were recruited from 56 UK breast units between 2013 and 2018. Of 2854/3369 eligible women with oestrogen receptor positive breast cancer, 2354 were treated with surgery and 500 with PET. Unadjusted surgery rates varied between hospitals, with 23/56 units falling outside the 95% confidence intervals on funnel plots. Adjusting for case mix reduced, but did not eliminate, this variation between hospitals (10/56 units had practice outside the 95% confidence intervals). Patients treated with PET had more patient-centred decisions compared to surgical patients (42.2% vs 28.4%, p

There are a range of views on the use of carbon offsetting among academics, higher and further education professional staff, corporates and offsetting providers. When and where offsets should be used or not used, and what types of offsets to use, are to some extent value-laden choices. These choices are being actively debated at the international and community level. This briefing note provides guidance to support the development of further and higher education offsetting policies and to challenge institutions, including our own. It specifically discusses the use of offsetting in the context of net zero strategies. We are also using the briefing to consult our institutions on the approaches they are taking. We hope it prompts discussion and collective action towards making net zero a reality.

Sussex Archaeological Collections, 117, 37-44

Sussex Archaeological Collections, 108, 23-38, A Roman tileworks operated here, perhaps during the 2nd century A.D., serving the needs of the settlement and posting station at Alfoldean on Stanestreet, 2 1/2 miles away. It was possible to examine the tilemakers' workshop and integral drying area, which was built some time after tilemaking had begun. Evidence suggests that, at this site, two combs were in simultaneous use for marking the keying grooves on flue-tiles. Features detected by proton gradiometer survey turned out to be dumps of tile debris.

Thiamine deficiency is a public health issue in Cambodia. Thiamine fortification of salt has been proposed; however, the salt intake of lactating women, the target population, is currently unknown. We estimated salt intakes among lactating women (

GWAS have identified >200 risk loci for Inflammatory Bowel Disease (IBD). The majority of disease associations are known to be driven by regulatory variants. To identify the putative causative genes that are perturbed by these variants, we generate a large transcriptome data set (nine disease-relevant cell types) and identify 23,650 cis-eQTL. We show that these are determined by ∼9720 regulatory modules, of which ∼3000 operate in multiple tissues and ∼970 on multiple genes. We identify regulatory modules that drive the disease association for 63 of the 200 risk loci, and show that these are enriched in multigenic modules. Based on these analyses, we resequence 45 of the corresponding 100 candidate genes in 6600 Crohn disease (CD) cases and 5500 controls, and show with burden tests that they include likely causative genes. Our analyses indicate that ≥10-fold larger sample sizes will be required to demonstrate the causality of individual genes using this approach., Most of the more than 200 known genetic risk loci for inflammatory bowel disease (IBD) reside in regulatory regions. Here, the authors provide eQTL datasets for six circulating immune cell types and ileal, colonic and rectal biopsies to map regulatory modules and identify potential causative genes for IBD.

Contains fulltext : 172376.pdf (Publisher’s version ) (Open Access)

This article investigates the impact of natural burial on the delivery of ecosystem services (ESs) in urban cemeteries in England that are owned and managed by local authorities. Local authority natural burial sites have received far less attention from researchers than independent sites developed by farmers, charitable trusts, funeral directors and land owners. Here we argue that the local authority hybrid cemeteries that combine natural burial with traditional graves may have a far greater impact in delivering regulatory and cultural ecosystem services than the much larger and frequently more environmentally ambitious natural burial grounds developed by the independent sector. The article presents three case studies of cemeteries, each of which represents a different interpretation of natural burial. Two have retrofitted natural burial into an existing cemetery landscape. The third is a new cemetery where natural burial was included with traditional burial in the original design brief and planning application. The research reveals how natural burial is transforming the traditional cemetery, with its focus on an intensively managed lawn aesthetic, towards a more habitat rich and spatially complex landscape with its own distinctive identity. The research also reveals how natural burial (within the unique constraints of UK burial culture that does not permit the recycling of burial space) is increasing the burial capacity of urban cemeteries by accessing land and grave space that might not be suitable or appropriate for more traditional forms of burial.

The goal of the current investigation was to establish proof of concept regarding measurement of blood lactate levels as an indicator of laryngeal muscle activity and fatigue, as well as to examine the relationship between blood lactate levels and NMES intensity. Fifteen participants completed a vocal loading exercise while blood lactate was measured prior to, during, and upon completion of the exercise. Acoustic measures of voice production and subjective reports of fatigue/soreness were obtained pre- and post-vocal loading task. The participants were divided into three groups: those who did not receive laryngeal neuromuscular electrical stimulation (NMES), those who received laryngeal NMES at a minimally perceivable level of intensity, and those who received laryngeal NMES at a maximum tolerable level of intensity. Changes in blood lactate levels were observed during the vocal loading task, thus indicating that blood lactate measurements are sensitive enough to reflect laryngeal muscle activity. No consistent pattern between blood lactate levels and NMES intensity or fatigue emerged. Several factors may account for these findings.

The dc tap or dc transformer will play an important role in interfacing different voltages of dc links in dc grids. This paper presents an isolated resonant mode modular converter (RMMC) with flexible modulation and assorted configurations to satisfy a wide variety of interface requirements for medium voltage dc (MVDC) networks. The transformer-less RMMC, as introduced in the literature, implemented a restricted modulation scheme leading to a very limited range of step-ratio and the diode rectifier resulted in unidirectional power flow. Both of these limitations are removed in this proposal and galvanic isolation has also been added. Moreover, this new RMMC approach can serve as a building block for variety of configurations. Two such derived topologies are given, which inherently balance the voltage and current between different constituent circuits and realize the high power rating conversion for very low or very high step-ratio application. The theoretical analysis is validated by a set of full-scale simulations and a down-scaled experimental prototype. The results illustrate that this isolated RMMC and its derivatives have promising features for dc taps or dc transformers in MVDC applications.

In future power systems, reduced overall inertia caused by an increased dominance of asynchronous generation and interconnections would make frequency control particularly challenging. As the number and power rating of voltage source converter (VSC) HVDC systems increases, network service provision would be expected from such systems and to do so would require overload capacity to be included in the converter specifications. This paper studies the provision of frequency services from modular multilevel converter (MMC)-based VSC HVDC interconnections using temperature-constrained overload capability. Overload of the MMC-based HVDC system is achieved through controlled circulating currents, at the expense of higher losses, and subject to a control scheme that dynamically limits the overload available in order to keep the semiconductor junction temperatures within operational limits. Two frequency control schemes that use the obtained overload capacity to provide frequency response during emergency conditions are investigated. The controllers' performance is demonstrated in the context of the future Great Britain transmission grid through a reduced equivalent test system. Simulation results show that even modest temperature margins which allow overload of MMC-based HVDC systems for a few seconds are effective as a primary frequency reserve and also reduce the loss of infeed requirements of such interconnections.

Background Thiamine deficiency is thought to be an issue in Cambodia and throughout Southeast Asia due to frequent clinical reports of infantile beriberi. However the extent of this public health issue is currently unknown due to a lack of population-representative data. Therefore we assessed the thiamine status (measured as erythrocyte thiamine diphosphate concentrations; eThDP) among a representative sample of Cambodian women of childbearing age (15-49 y) and their young children (6-69 mo). Methodology/Principle findings Samples for this cross-sectional analysis were collected as part of a national micronutrient survey linked to the Cambodian Demographic and Health Survey (CDHS) 2014. One-sixth of households taking part in the CDHS were randomly selected and re-visited for additional blood sampling for eThDP analysis (719 women and 761 children). Thiamine status was assessed using different cut-offs from literature. Women were mean (SD) 30 (6) y, and children (46% girls) were 41 (17) mo. Women had lower mean (95% Cl) eThDP of 150 nmol/L (146-153) compared to children, 174 nmol/L (171-179; P < 0.001). Using the most conservative cut-off of eThDP < 120 nmol/ L, 27% of mothers and 15% of children were thiamine deficient, however prevalence rates of deficiency were as high as 78% for mothers and 58% for children using a cut-off of < 180 nmol/L. Thiamine deficiency was especially prevalent among infants aged 6-12 mo: 38% were deficient using the most conservative cut-off (< 120 nmol/L). Conclusions/Significance There is a lack of consensus on thiamine status cut-offs; more research is required to set clinically meaningful cut-offs. Despite this, there is strong evidence of suboptimal thiamine status among Cambodian mothers and their children, with infants

Theresa Green1, Shreyas Gandhi2, Tessa Kleissen1, Jessica Simon1,3, Shelley Raffin-Bouchal1, Karla Ryckborst41Faculty of Nursing, University of Calgary, Calgary, AB, Canada; 2Health Sciences, McMaster University, Hamilton, ON, Canada; 3Department of Medicine, University of Calgary, Calgary, AB, Canada; 4Calgary Stroke Program, Alberta Health Services, Calgary, AB, CanadaPurpose: Individuals who experience stroke have a higher likelihood of subsequent stroke events, making it imperative to plan for future medical care. In the event of a further serious health event, engaging in the process of advanced care planning (ACP) can help family members and health care professionals (HCPs) make medical decisions for individuals who have lost the capacity to do so. Few studies have explored the views and experiences of patients with stroke about discussing their wishes and preferences for future medical events, and the extent to which stroke HCPs engage in conversations around planning for such events. In this study, we sought to understand how the process of ACP unfolded between HCPs and patients post-stroke.Patients and methods: Using grounded theory (GT) methodology, we engaged in direct observation of HCP and patient interactions on an acute stroke unit and two stroke rehabilitation units. Using semi-structured interviews, 14 patients and four HCPs were interviewed directly about the ACP process.Results: We found that open and continual ACP conversations were not taking place, patients experienced an apparent lack of urgency to engage in ACP, and HCPs were uncomfortable initiating ACP conversations due to the sensitive nature of the topic.Conclusion: In this study, we identified lack of engagement in ACP post-stroke, attributable to patient and HCP factors. This encourages us to look further into the process of ACP in order to develop open communication between the patient with stroke, their families, and stroke HCPs.Keywords: qualitative, engagement, health care providers, palliative

A growing body of literature indicates that leader spirituality positively influences how leaders lead. There is also a body of literature that indicates that followers associate good leadership with behaving ethically. A concept related to leader ethics is leader virtues. Historically, virtues have been written about from a theological perspective. Recently, Riggio, Zhu, Reina and Maroosis (2010) developed an empirical assessment to measure leadership virtues. In this study, 143 leaders were rated by their followers, peers and supervisors using the 'Multifactor Leadership Questionnaire and the Leadership Virtues Questionnaire'. The leaders completed three spiritual and religious assessments on themselves. The results of the analysis found that leader spiritual well-being had direct effects on how virtuously and how actively followers, colleagues and supervisors rated these leaders.

Nuclear magnetic resonance (NMR) is a popular spectroscopic method and has widespread use in many fields. Recent developments in solid-state NMR have increased interest in experiment and, alongside simultaneous developments in computational theory, have led to the field dubbed 'NMR crystallography.' This is a suite of methodologies, complementing the capabilities of other crystallographic methods in the determination of atomic structure, especially when large crystals cannot be made and when exploring materials with phenomena such as compositional, positional and dynamic disorder. NMR J-coupling is the indirect coupling between nuclear spins, which, when measured, can reveal a wealth of information about structure and bonding. This thesis develops and applies the method of Joyce for the prediction of NMR J-coupling in condensed matter systems using plane-wave pseudopotential density-functional theory, an important requirement for efficient treatment of finite and infinite periodic systems. It describes the first-ever method for the use of ultrasoft pseudopotentials and inclusion of special relativistic effects in J-coupling prediction, allowing for the treatment of a wider range of materials systems and overall greater user friendliness, thus making the method more accessible and attractive to the wider scientific community.

This study compared acute postexercise oxygen consumption in 11 trained women (age, 46.5 ± 1.6 years; body mass index [BMI], 28.4 ± 1.7 kg·m(-2) and 11 untrained women (age, 46.5 ± 1.5 years; BMI, 27.5 ± 1.5 kg·m(-2)) after resistance exercise (RE). Resistance exercise consisted of 3 sets of 8 exercises (8-12 repetitions at 50-80% 1 repetition maximum). Oxygen consumption (VO2 ml·min(-1)) was measured before and after (0, 20, 40, 60, 90, and 120 minutes) RE. Immediately after cessation of RE (time 0), oxygen consumption increased in both trained and untrained women and remained significantly above baseline through 60 minutes after exercise (p < 0.01). Total oxygen consumption during recovery was 31.3 L in trained women and 27.4 L in untrained women (p = 0.07). In trained women, total oxygen consumption was strongly related to absolute (kg) lean mass (r = 0.88; p < 0.001), relative (kilogram per square meter) lean mass (r = 0.91; p < 0.001), and duration of exercise (r = 0.68; p ≤ 0.05), but in untrained women, only training volume-load was related to total oxygen consumption (r = 0.67; p ≤ 0.05). In trained women, 86% of the variance in oxygen consumption was explained by lean mass and exercise duration, whereas volume-load explained 45% in untrained women. Our findings suggest that, in women, resistance training increases metabolic activity of lean tissue. Postexercise energy costs of RE are determined by the duration of stimulation provided by RE rather than absolute work (volume-load) performed. This phenomenon may be related to type II muscle fibers and increased protein synthesis.

Background: Crohn's disease and ulcerative colitis are the two major forms of inflammatory bowel disease; treatment strategies have historically been determined by this binary categorisation. Genetic studies have identified 163 susceptibility loci for inflammatory bowel disease, mostly shared between Crohn's disease and ulcerative colitis. We undertook the largest genotype association study, to date, in widely used clinical subphenotypes of inflammatory bowel disease with the goal of further understanding the biological relations between diseases.Methods: This study included patients from 49 centres in 16 countries in Europe, North America, and Australasia. We applied the Montreal classification system of inflammatory bowel disease subphenotypes to 34 819 patients (19 713 with Crohn's disease, 14 683 with ulcerative colitis) genotyped on the Immunochip array. We tested for genotype–phenotype associations across 156 154 genetic variants. We generated genetic risk scores by combining information from all known inflammatory bowel disease associations to summarise the total load of genetic risk for a particular phenotype. We used these risk scores to test the hypothesis that colonic Crohn's disease, ileal Crohn's disease, and ulcerative colitis are all genetically distinct from each other, and to attempt to identify patients with a mismatch between clinical diagnosis and genetic risk profile.Findings: After quality control, the primary analysis included 29 838 patients (16 902 with Crohn's disease, 12 597 with ulcerative colitis). Three loci (NOD2, MHC, and MST1 3p21) were associated with subphenotypes of inflammatory bowel disease, mainly disease location (essentially fixed over time; median follow-up of 10·5 years). Little or no genetic association with disease behaviour (which changed dramatically over time) remained after conditioning on disease location and age at onset. The genetic risk score representing all known risk alleles for inflammatory bowel disease showed strong association with disease subphenotype (p=1·65 × 10−78), even after exclusion of NOD2, MHC, and 3p21 (p=9·23 × 10−18). Predictive models based on the genetic risk score strongly distinguished colonic from ileal Crohn's disease. Our genetic risk score could also identify a small number of patients with discrepant genetic risk profiles who were significantly more likely to have a revised diagnosis after follow-up (p=6·8 × 10−4).Interpretation: Our data support a continuum of disorders within inflammatory bowel disease, much better explained by three groups (ileal Crohn's disease, colonic Crohn's disease, and ulcerative colitis) than by Crohn's disease and ulcerative colitis as currently defined. Disease location is an intrinsic aspect of a patient's disease, in part genetically determined, and the major driver to changes in disease behaviour over time.Funding: International Inflammatory Bowel Disease Genetics Consortium members funding sources (see Acknowledgments for full list).

RCW 86 is a young supernova remnant (SNR) showing a shell-type structure at several wavelengths and is thought to be an efficient cosmic-ray (CR) accelerator. Earlier \textit{Fermi} Large Area Telescope results reported the detection of $\gamma$-ray emission coincident with the position of RCW 86 but its origin (leptonic or hadronic) remained unclear due to the poor statistics. Thanks to 6.5 years of data acquired by the \textit{Fermi}-LAT and the new event reconstruction Pass 8, we report the significant detection of spatially extended emission coming from RCW 86. The spectrum is described by a power-law function with a very hard photon index ($\Gamma = 1.42 \pm 0.1_{\rm stat} \pm 0.06_{\rm syst}$) in the 0.1--500 GeV range and an energy flux above 100 MeV of ($2.91$ $\pm$ $0.8_{\rm stat}$ $\pm$ $0.12_{\rm syst}$) $\times$ $10^{-11}$ erg cm$^{-2}$ s$^{-1}$. Gathering all the available multiwavelength (MWL) data, we perform a broadband modeling of the nonthermal emission of RCW 86 to constrain parameters of the nearby medium and bring new hints about the origin of the $\gamma$-ray emission. For the whole SNR, the modeling favors a leptonic scenario in the framework of a two-zone model with an average magnetic field of 10.2 $\pm$ 0.7 $\mu$G and a limit on the maximum energy injected into protons of 2 $\times$ 10$^{49}$ erg for a density of 1 cm$^{-3}$. In addition, parameter values are derived for the North-East (NE) and South-West (SW) regions of RCW 86, providing the first indication of a higher magnetic field in the SW region., Comment: 13 pages, 10 figures, accepted for publication in ApJ; Corresponding authors : Benjamin Condon, Marianne Lemoine-Goumard, Micaela Caragiulo

info:eu-repo/semantics/publishedVersion

Supporting material: figures and tables., A previously established chronosequence from Pia Glacier forefield in Tierra del Fuego (Chile) containing soils of different ages (from bare soils to forest ones) is analyzed. We used this chronosequence as framework to postulate that microbial successional development would be accompanied by changes in functionality. To test this, the GeoChip functional microarray was used to identify diversity of genes involved in microbial carbon and nitrogen metabolism, as well as other genes related to microbial stress response and biotic interactions. Changes in putative functionality generally reflected succession-related taxonomic composition of soil microbiota. Major shifts in carbon fixation and catabolism were observed, as well as major changes in nitrogen metabolism. At initial microbial dominated succession stages, microorganisms could be mainly involved in pathways that help to increase nutrient availability, while more complex microbial transformations such as denitrification and methanogenesis, and later degradation of complex organic substrates, could play more important roles at vegetated successional states. Shifts in virus populations broadly reflected changes in microbial diversity. Conversely, stress response pathways appeared relatively well conserved for communities along the entire chronosequence. We conclude nutrient utilization is likely the major driver of microbial succession in these soils.

The European Hematology Association (EHA) Roadmap for European Hematology Research highlights major achievements in diagnosis and treatment of blood disorders and identifies the greatest unmet clinical and scientific needs in those areas to enable better funded, more focused European hematology research. Initiated by the EHA, around 300 experts contributed to the consensus document, which will help European policy makers, research funders, research organizations, researchers, and patient groups make better informed decisions on hematology research. It also aims to raise public awareness of the burden of blood disorders on European society, which purely in economic terms is estimated at ∈ European Hematology Association (EHA) Roadmap for European Hematology Research highlights major achievements in diagnosis and treatment of blood disorders and identifies the greatest unmet clinical and scientific needs in those areas to enable better fu treatments, sometimes in revolutionary ways. This progress highlights the potential of focused basic research programs such as this EHA Roadmap. The EHA Roadmap identifies nine ‘sections’ in hematology: normal hematopoiesis, malignant lymphoid and myeloid diseases, anemias and related diseases, platelet disorders, blood coagulation and hemostatic disorders, transfusion medicine, infections in hematology, and hematopoietic stem cell transplantation. These sections span 60 smaller groups of diseases or disorders. The EHA Roadmap identifies priorities and needs across the field of hematology, including those to develop targeted therapies based on genomic profiling and chemical biology, to eradicate minimal residual malignant disease, and to develop cellular immunotherapies, combination treatments, gene therapies, hematopoietic stem cell treatments, and treatments that are better tolerated by elderly patients. © 2016 Ferrata Storti Foundation.

We introduce two open source tools to aid the processing and visualisation of ab-initio computed solid-state NMR parameters. The Magres file format for computed NMR parameters (as implemented in CASTEP v8.0 and QuantumEspresso v5.0.0) is implemented. MagresView is built upon the widely used Jmol crystal viewer, and provides an intuitive environment to display computed NMR parameters. It can provide simple pictorial representation of one- and two-dimensional NMR spectra as well as output a selected spin-system for exact simulations with dedicated spin-dynamics software. MagresPython provides a simple scripting environment to manipulate large numbers of computed NMR parameters to search for structural correlations.

Although a dose-response relationship between resistance training frequency and strength has been identified, there is limited research regarding the association between frequency and body composition. This study evaluated the effects of 3 vs. 4 d·wk(-1) of resistance training on body composition and strength in middle-aged women. Twenty-one untrained women (age 47.6 ± 1.2 years) completed 8 weeks of resistance training either 3 nonconsecutive days of the week using a traditional total-body protocol (RT3) or 4 consecutive days of the week using an alternating split-training protocol (RT4). The RT3 completed 3 sets of 8 exercises, whereas RT4 completed 3 sets of 6 upper body exercises or 6 sets of 3 lower body exercises. Both groups completed 72 sets per week of 8-12 repetitions at 50-80% 1 repetition maximum. Weekly training volume load was calculated as the total number of repetitions × load (kg) completed per week. Body composition was measured using air displacement plethysmography. At baseline and after 8 weeks of resistance training, there were no significant between-group differences. Both protocols resulted in significant increases in absolute lean mass (1.1 ± 0.3 kg; p = 0.001), body weight (1.02 ± 0.3 kg; p = 0.005), body mass index (0.3 ± 0.1 kg·m(-2); p = 0.006), strength (p < 0.001), and weekly training volume load (p < 0.001). Correlation analysis revealed that weekly training volume load was strongly and positively related to gains in lean mass (r = 0.56, p = 0.05) and strength (r = 0.60, p = 0.006). In these untrained, middle-aged women, initial short-term gains in lean mass and strength were not influenced by training frequency when the number of training sets per week was equated.

To access publisher full text version of this article. Please click on the hyperlink in Additional Links field Effects of susceptibility variants may depend on from which parent they are inherited. Although many associations between sequence variants and human traits have been discovered through genome-wide associations, the impact of parental origin has largely been ignored. Here we show that for 38,167 Icelanders genotyped using single nucleotide polymorphism (SNP) chips, the parental origin of most alleles can be determined. For this we used a combination of genealogy and long-range phasing. We then focused on SNPs that associate with diseases and are within 500 kilobases of known imprinted genes. Seven independent SNP associations were examined. Five-one with breast cancer, one with basal-cell carcinoma and three with type 2 diabetes-have parental-origin-specific associations. These variants are located in two genomic regions, 11p15 and 7q32, each harbouring a cluster of imprinted genes. Furthermore, we observed a novel association between the SNP rs2334499 at 11p15 and type 2 diabetes. Here the allele that confers risk when paternally inherited is protective when maternally transmitted. We identified a differentially methylated CTCF-binding site at 11p15 and demonstrated correlation of rs2334499 with decreased methylation of that site. info:eu-repo/grantAgreement/EC/FP7/218071