Search

Drug reaction with eosinophilia and systemic symptoms (DRESS) is a potentially life-threatening adverse drug reaction with a mortality rate of 10%. Interstitial nephritis, pneumonitis, myocarditis, meningitis, thyroiditis and pancreatitis are major causes of morbidity and mortality in this syndrome. Cessation of offending medication is paramount. There is paucity in high quality prospective studies guiding the treatment of DRESS, and there are no published therapeutic clinical trials in the treatment of corticosteroid refractory hypersensitivity myocarditis. The authors present a unique case of ciprofloxacin-induced DRESS with concurrent thyroiditis and refractory eosinophilic myocarditis that required mepolizumab and multiple immunosuppressants for successful treatment.

Rectus femoris (RF) injuries are common in sports requiring maximal acceleration and sprinting. The British Athletics Muscle Injury Classification (BAMIC) describes acute muscle injury based on the anatomical site of injury and has been associated with return to play in hamstring and calf muscle injury. The aim of this study was to describe and compare the time to return to full training (TRFT) and injury recurrence for BAMIC-classified RF injuries sustained by elite track and field (T&F) athletes over a 9-year period. All rectus femoris injuries sustained by elite T&F athletes on the British Athletics World Class Program between September 2010 and September 2019 that were investigated with an MRI within 7 days of acute onset anterior thigh pain were included. Injuries were graded from the MRI by a specialist musculoskeletal radiologist using the BAMIC, and TRFT and injury recurrence were determined by evaluation of the Electronic Medical Record. Athlete demographics and World Athletics event discipline were recorded. Specific injury details including mechanism, location of injury, and whether surgical or rehabilitation management was undertaken were recorded. There were 38 RF injuries in 27 athletes (24.7 ± 2.3 years; 10 male, 17 female). Average TRFT for rehabilitation managed cases was 20.4 ± 14.8 days. Grade 1 injuries had significantly shorter TRFT compared with grades 2 (p = 0.04) and 3 (p = 0.01). Intratendinous (c) and surgically managed RF injuries each had significantly longer TRFT compared with other injury classes (p

With blood products being a limited and expensive resource within the healthcare system, there is an ever-increasing emphasis on judicial and appropriate use.To evaluate whether implementing contemporary society recommendations on restrictive transfusion policies would reduce inappropriate use of red blood cell transfusions, by evaluating the effect of a staff educational campaign.An audit of peri-partum red cell concentrate (RCC) transfusion practice within a tertiary obstetric unit was undertaken, covering a 1-year period (2015), examining data related to transfusion prescribing practices. Subsequently, an educational programme was held for clinical and laboratory staff which aimed to bring practice in line with society guidelines. A repeat audit covering another 1-year period (2018) was undertaken.The number of RCC units of transfused reduced by 49% between 2015 and 2018 (426 to 218). The number of patients receiving transfusion dropped from 166 in 2018 (1.8% of births) to 119 in 2015 (1.5% of births). Among stable patients who were transfused, the proportion receiving a single unit increased from 6.9 to 53.9%. (p 0.001). Haematological reassessment between units rose from 13.8 to 80.4% (p 0.001). Written consent documentation improved (68% in 2018 vs. 38% in 2015) (p 0.001).The implementation of guidelines has resulted in substantial reduction in RCC transfusions between 2015 and 2018. Fewer women received a blood transfusion, and those who did received fewer units. There is a higher proportion of patients being reassessed between units and receiving single unit transfusions. Recording of consent has improved.

Our visual system relies on memory to store and retrieve goal-relevant structures and information from the environment for the purpose of optimizing the allocation of attention. This concept, referred to as contextual cueing, has been demonstrated using visual search tasks, wherein repeated visual contexts lead to reduced search times compared with random displays. Subsequently, when an unexpected change occurs in the environment, or memory fails, a cognitive expense is incurred as the mind tries to resolve the conflict with the memory of the previous environmental context. How memory resolves these conflicts and is updated is of great interest. Previous studies showed that, without extensive practice, individuals were unable to associate a secondary target location with a previously learned spatial context following the relocation of the initially learned target. Here, we explored variables that could potentially affect contextual learning and relearning, such as display size, crowding, context color, and whether the target switched to a previously occupied or unoccupied location. In a series of four experiments, we find relearning occurring in all instances. Previous research may have suffered from underpowered designs.

We give necessary and sufficient conditions for a cdh sheaf to satisfy Milnor excision, following ideas of Bhatt and Mathew. Along the way, we show that the cdh infinity-topos of a quasi-compact quasi-separated scheme of finite valuative dimension is hypercomplete, extending a theorem of Voevodsky to nonnoetherian schemes. As an application, we show that if E is a motivic spectrum over a field k which is n-torsion for some n invertible in k, then the cohomology theory on k-schemes defined by E satisfies Milnor excision., Comment: 28 pages. v3: final version, to appear in Mathematische Annalen; v2: new title and minor corrections

Objectives This novel study aims to provide unique data on eccentric hamstring strength in elite track and field athletes. Design Clinical measurement, cross-sectional study. Setting Across two British Athletics performance centres. Participants 44 elite British track and field athletes. Main outcome measures Eccentric hamstring force and torque were evaluated using the Nordbord device. Injury history and demographic data was collected to assess whether differences between gender, event group, limb symmetry and previous injury history were present. Results Average peak force for males and females was 418.38N and 318.54N. Relative to body weight there were no gender differences (Male 5.21N.kg−1, Female 4.99N.kg−1) (p = 0.62). The right limb was significantly stronger in long sprint (400m athletes) (p = 0.00018) (d = 0.56). No differences in relative force or torque were observed between previously injured and non-injured limbs. Conclusions This study provides unique data in elite track and field athletes. Relative force per kilogram should be used when comparing male and female athletes. Unlike other studies, we found no difference in eccentric strength between previously injured and non-injured limbs. The novel finding of increased eccentric strength demonstrated in the right limb in 400m sprinters may be due to the asymmetric demands of bend running and may be considered normal.

The failure of depleted bivalve populations to recover naturally is often due to a breakdown in recruitment processes, such as a lack of larvae or suitable settlement substrate. The identification of these recruitment limitations are a critical initial step for determining an appropriate strategy for restoration. A lack of larval supply and settlement substrate have both been suggested as possible causes of the failure of natural recovery in the green‐lipped mussel population in the Hauraki Gulf, New Zealand, and were therefore examined in this study. Larval mussels settled throughout most of the year directly onto artificial collectors placed within restored adult mussel beds and in the immediate vicinity of the beds at comparatively lower levels than for remnant populations throughout New Zealand. This low settlement coupled with a lack of recruitment to the restored mussel beds suggests larval supply may be limited in the Hauraki Gulf and warrants further examinations into larval dispersal and retention. Larval settlement was also higher on collectors within mussel beds, suggesting the presence of adults enhances larval settlement and highlights the importance of transplanting adult mussels for reestablishing mussel populations.

The double-step paradigm investigates the characteristics of planning and execution when the motor system must rapidly adjust for a new goal location. Studies have provided detailed temporal information based on the duration available for the motor system to prepare a new movement trajectory (here referred to as re-preparation time). However, previous work has largely examined single displacement sizes, limiting the spatiotemporal understanding of movement planning and execution. The lack of a description of this behavioral timecourse across increasing displacement sizes is true for saccades, rapid eye movements that redirect the fovea. Furthermore, during the double-step paradigm, the primary saccade often fails to accurately foveate the final target location and a secondary saccade brings the target onto the fovea. However, it is also unknown how this compensation is concurrently modified with the exposure duration and displacement of the movement goal. Here, we examined the amount of time required to change the initial saccade direction to a new target location for relatively small (20°, 30°, and 40°) and large (60° and 90°) target spatial separations. Interestingly, we found a clear relationship between the saccade direction and the amount of time allowed to redirect the movement; across separations, intermediate saccades occurred when approximately 60–140 ms was available to readjust the movement plan. Additionally, there was a consistent relationship between the timing of the secondary saccade and the re-preparation time across jump sizes, suggesting that concurrent movement correction planning was dependent on the amount of exposure to the final movement goal.

In order to work with non-Nagata rings which are Nagata “up-to-completely-decomposed-universal-homeomorphism,” specifically finite rank Hensel valuation rings, we introduce the notions of pseudo-integral closure, pseudo-normalization, and pseudo-Hensel valuation ring. We use this notion to give a shorter and more direct proof that $H_{\operatorname{cdh}}^{n}(X,F_{\operatorname{cdh}})=H_{l\operatorname{dh}}^{n}(X,F_{l\operatorname{dh}})$ for homotopy sheaves $F$ of modules over the $\mathbb{Z}_{(l)}$-linear motivic Eilenberg–Maclane spectrum. This comparison is an alternative to the first half of the author’s volume Astérisque 391 whose main theorem is a cdh-descent result for Voevodsky motives. The motivating new insight is really accepting that Voevodsky’s motivic cohomology (with $\mathbb{Z}[\frac{1}{p}]$-coefficients) is invariant not just for nilpotent thickenings, but for all universal homeomorphisms.

RationaleHamstring injuries are common in elite sports. Muscle injury classification systems aim to provide a framework for diagnosis. The British Athletics Muscle Injury Classification (BAMIC) describes an MRI classification system with clearly defined, anatomically focused classes based on the site of injury: (a) myofascial, (b) muscle–tendon junction or (c) intratendinous; and the extent of the injury, graded from 0 to 4. However, there are no clinical guidelines that link the specific diagnosis (as above) with a focused rehabilitation plan.ObjectiveWe present an overview of the general principles of, and rationale for, exercise-based hamstring injury rehabilitation in British Athletics. We describe how British Athletics clinicians use the BAMIC to help manage elite track and field athletes with hamstring injury. Within each class of injury, we discuss four topics: clinical presentation, healing physiology, how we prescribe and progress rehabilitation and how we make the shared decision to return to full training. We recommend a structured and targeted diagnostic and rehabilitation approach to improve outcomes after hamstring injury.

This paper provides a description and analyses of NASA's (National Aeronautics and Space Administration) high-rate Ka-band downlink system for the upcoming NISAR (NASA-ISRO Synthetic Aperture Radar) mission developed at the Jet Propulsion Laboratory (JPL). NISAR is a collaborative Earth-Science mission between NASA and the Indian Space Research Organisation (ISRO), which features an L-band SAR instrument and an S-band SAR instrument. The simultaneous dual-frequency radar system at peak rates will produce data at gigabit-per-second speeds, which drives the data-volume requirements. The key driving requirement for the Payload Communication Subsystem is to provide a minimum of 35 Terabits per day of radar science data to the ground. NASA's high-rate transmitter on the flight system is a software-defined radio based on the Universal Space Transponder platform, providing an offset quadrature phase shift key modulated waveform with Low-Density Parity Check encoding of the data transfer frames. Two transmitters used in a dual-polarization configuration with each transmitter providing two giga-symbols per second (Gsps) of coded data provides an aggregate rate of four Gsps. In this system, using the ISRO-provided 70-cm high-gain antenna, only 1 W of signal power is necessary on each polarization to overcome propagation losses and achieve a successful RF link. Several Near Earth Network (NEN) ground station sites (Alaska in the United States, Svalbard in Norway, and Punta Arenas in Chile) are baselined for the space-to-Earth communications link. Each ground station will also feature multiple upgrades to support NISAR's transmission starting with new Ka-band antennas, and new electronic units such as wideband downconverters and high-rate receivers. In addition, a baseband data processor called Data Acquisition Processor and Handling Network Environment (DAPHNE), newly developed by the NEN, provides data storage and connectivity to backhaul networks. With NISAR's unprecedented large volume of data (nearly 5 Petabytes over the mission duration), a cloud system enables science data processing cost reduction to the mission. The NASA downlink system described herein will be the first operational use of Gsps-class downlink rates on an Earth-Science mission.

Digital, Objectives To describe the incidence rate, severity, burden and aetiology of medical attention and time-loss injuries across five consecutive seasons at a professional ballet company. Methods Medical attention injuries, time-loss injuries and dance exposure hours of 123 professional ballet dancers (women: n=66, age: 28.0±8.3 years; men: n=57, age: 27.9±8.5 years) were prospectively recorded between the 2015/2016 and 2019/2020 seasons. Results The incidence rate (per 1000 hours) of medical attention injury was 3.9 (95% CI 3.3 to 4.4) for women and 3.1 (95% CI 2.6 to 3.5) for men. The incidence rate (per 1000 hours) of time-loss injury was 1.2 (95% CI 1.0 to 1.5) for women and 1.1 (95% CI 0.9 to 1.3) for men. First Soloists and Principals experienced between 2.0–2.2 additional medical attention injuries per 1000 hours and 0.9–1.1 additional time-loss injuries per 1000 hours compared with Apprentices (p≤0.025). Further, intraseason differences were observed in medical attention, but not time-loss, injury incidence rates with the highest incidence rates in early (August and September) and late (June) season months. Thirty-five per cent of time-loss injuries resulted in over 28 days of modified dance training. A greater percentage of time-loss injuries were classified as overuse (women: 50%; men: 51%) compared with traumatic (women: 40%; men: 41%). Conclusion This is the first study to report the incidence rate of medical attention and time-loss injuries in professional ballet dancers. Incidence rates differed across company ranks and months, which may inform targeted injury prevention strategies., Ciencias Médicas y de la Salud

We prove several results showing that the algebraic$K$-theory of valuation rings behaves as though such rings were regular Noetherian, in particular an analogue of the Geisser–Levine theorem. We also give some new proofs of known results concerning cdh descent of algebraic$K$-theory.

Objective: We aimed to describe hamstring muscle injury (HMI) history and hamstring specific training (HST) in elite athletes. A secondary aim was to analyse the potential factors associated with in-championships HMI. Methods: We conducted a prospective cohort study to collect data before and during the 2018 European Athletics Championships. Injury and illness complaints during the month before the championship, HMI history during the entire career and the 2017–18 season, HST (strengthening, stretching, core stability, sprinting), and in-championship HMI were recorded. We calculated proportions of athletes with HMI history, we compared HST according to sex and disciplines with Chi2 tests or ANOVA, and analysed factors associated with in-championship HMI using simple model logistic regression. Results: Among the 357 included athletes, 48% reported at least one HMI during their career and 24% during the 2017–18 season. Of this latter group, 30.6% reported reduced or no participation in athletics’ training or competition at the start of the championship due to the hamstring injury. For HST, higher volumes of hamstring stretching and sprinting were reported for disciplines requiring higher running velocities (i.e., sprints, hurdles, jumps, combined events and middle distances). Five in-championship HMIs were recorded. The simple model analysis showed a lower risk of sustaining an in-championships HMI for athletes who performed more core (lumbo-pelvic) stability training (OR = 0.49 (95% CI: 0.25 to 0.89), p = 0.021). Conclusions: Our present study reports that HMI is a characteristic of the athletics athletes’ career, especially in disciplines involving sprinting. In these disciplines, athletes were performing higher volumes of hamstring stretching and sprinting than in other disciplines. Further studies should be conducted to better understand if and how HST are protective approaches for HMI in order to improve HMI risk reduction strategies.

ObjectivesThe British Athletics Muscle Injury Classification (BAMIC) correlates with return to play in muscle injury. The aim of this study was to examine hamstring injury diagnoses and outcomes within elite track and field athletes following implementation of the British Athletics hamstring rehabilitation approach.MethodsAll hamstring injuries sustained by elite track and field athletes on the British Athletics World Class Programme between December 2015 and November 2019 that underwent an MRI and had British Athletics medical team prescribed rehabilitation were included. Athlete demographics and specific injury details, including mechanism of injury, self-reported gait phase, MRI characteristics and time to return to full training (TRFT) were contemporaneously recorded.Results70 hamstring injuries in 46 athletes (24 women and 22 men, 24.6±3.7 years) were included. BAMIC grade and the intratendon c classification correlated with increased TRFT. Mean TRFT was 18.6 days for the entire cohort. Mean TRFT for intratendon classifications was 34±7 days (2c) and 48±17 days (3c). The overall reinjury rate was 2.9% and no reinjuries were sustained in the intratendon classifications. MRI variables of length and cross-sectional (CSA) area of muscle oedema, CSA of tendon injury and loss of tendon tension were associated with TRFT. Longitudinal length of tendon injury, in the intratendon classes, was not associated with TRFT.ConclusionThe application of BAMIC to inform hamstring rehabilitation in British Athletics results in low reinjury rates and favourable TRFT following hamstring injury. The key MRI variables associated with longer recovery are length and CSA of muscle oedema, CSA of tendon injury and loss of tendon tension.

Contains fulltext : 234338.pdf (Publisher’s version ) (Closed access) Purpose: To describe the relationships between dance exposure, dancer characteristics, and injury risk across five seasons in a professional ballet company. Methods: Dance exposure time and clinician-reported time-loss and medical attention injury data were prospectively collected from 118 professional dancers of The Royal Ballet between 2015/16 and 2019/20. Cox proportional hazards and shared frailty models were fitted to overuse and traumatic injuries; individualized robust Z-scores for 7-day and 28-day accumulated exposure, and week-to-week change in exposure, age, sex, company rank, and injury history were included as time-varying covariates. Results: Across 381,710 h of exposure, 1332 medical attention and 427 time-loss injuries were observed. Positive relationships were observed between week-to-week change in exposure and overuse time-loss (+1 Z-score hazard ratio (HR): 1.27, 95% confidence interval (CI): 1.06-1.53) and medical attention injury risk (+1 Z-score HR: 1.17, 95% CI: 1.06-1.28). A negative relationship was observed between 7-day accumulated exposure and overuse medical-attention injury risk (+1 Z-score HR: 0.74, 95% CI: 0.66-0.84). Overuse time-loss injury risk was greater in soloists compared to the corps de ballet (HR: 1.47, 95% CI: 1.01-2.15), and in dancers with a higher previous injury rate (+1 injury·1000 h-1 HR: 1.06, 95% CI: 1.02–1.10). Only age was associated with traumatic time-loss (+1-year HR: 1.05, 95% CI: 1.01-1.09) or medical attention injury risk (+1-year HR: 1.04, 95% CI: 1.01-1.07). Conclusion: Professional ballet companies should implement training principles such as periodization and progression, particularly in the case of senior-ranking dancers, older dancers, and dancers with high rates of previous injury. These findings provide a basis for future prospective investigations into specific causal injury pathways. 8 p.

Background & Aims Continuing recalcitrance to therapy cements pancreatic cancer (PC) as the most lethal malignancy, which is set to become the second leading cause of cancer death in our society. The study aim was to investigate the association between DNA damage response (DDR), replication stress, and novel therapeutic response in PC to develop a biomarker-driven therapeutic strategy targeting DDR and replication stress in PC. Methods We interrogated the transcriptome, genome, proteome, and functional characteristics of 61 novel PC patient–derived cell lines to define novel therapeutic strategies targeting DDR and replication stress. Validation was done in patient-derived xenografts and human PC organoids. Results Patient-derived cell lines faithfully recapitulate the epithelial component of pancreatic tumors, including previously described molecular subtypes. Biomarkers of DDR deficiency, including a novel signature of homologous recombination deficiency, cosegregates with response to platinum (P < .001) and PARP inhibitor therapy (P < .001) in vitro and in vivo. We generated a novel signature of replication stress that predicts response to ATR (P < .018) and WEE1 inhibitor (P < .029) treatment in both cell lines and human PC organoids. Replication stress was enriched in the squamous subtype of PC (P < .001) but was not associated with DDR deficiency. Conclusions Replication stress and DDR deficiency are independent of each other, creating opportunities for therapy in DDR-proficient PC and after platinum therapy., Graphical abstract

Why do saccades interfere with spatial working memory? One possibility is that attention and saccades are tightly coupled, and performing a saccade momentarily removes attention from spatial working memory, degrading the memory representation. This cannot be the entire explanation, because saccades cause greater interference than do covert attentional shifts (Lawrence, Myerson, & Abrams, 2004). In addition, this saccadic degradation is limited to spatial but not object, configural, or verbal representations. We propose that saccadic remapping is partially responsible for this increased interference. To test this, we used a spatial change detection task, and during the retention interval, participants either performed a central task, a peripheral task without an eye movement, or a peripheral task that required a saccade. Using the method of constant stimuli allowed us to fit psychophysical functions in which we derived measures of spatial memory precision, guessing, and response bias. It is important that we found a directionally specific loss of memory precision, such that memory representations were less precise along the axis of the saccade. This was beyond the general loss of precision we found for covert shifts, suggesting that part of the effect is because of remapping. Saccades also increased guessing, but unlike the loss of precision, the effect was nondirectional. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

We prove that the $\infty$-category of motivic spectra satisfies Milnor excision: if $A\to B$ is a morphism of commutative rings sending an ideal $I\subset A$ isomorphically onto an ideal of $B$, then a motivic spectrum over $A$ is equivalent to a pair of motivic spectra over $B$ and $A/I$ that are identified over $B/IB$. Consequently, any cohomology theory represented by a motivic spectrum satisfies Milnor excision. We also prove Milnor excision for Ayoub's \'etale motives over schemes of finite virtual cohomological dimension., Comment: 11 pages. Final version, to appear in J. reine angew. Math

This paper continues our study of the sheaf associated to K\"ahler differentials in the cdh-topology and its cousins, in positive characteristic, without assuming resolution of singularities. The picture for the sheaves themselves is now fairly complete. We give a calculation $\mathcal{O}_{cdh}(X) \cong \mathcal{O}(X^{sn})$ in terms of the seminormalisation. We observe that the category of representable cdh-sheaves is equivalent to the category of seminormal varieties. We conclude by proposing some possible connections to Berkovich spaces, and $F$-singularities in the last section. The tools developed for the case of differential forms also apply in other contexts and should be of independent interest., Comment: 37 pages

We give a brief introduction to tensor triangulated geometry, a brief introduction to various motivic categories, and then make some observations about the conjectural structure of the tensor triangulated spectrum of the Morel–Voevodsky stable homotopy category over a finite field.

Pancreatic ductal adenocarcinoma (PDAC) can be divided into transcriptomic subtypes with two broad lineages referred to as classical (pancreatic) and squamous. We find that these two subtypes are driven by distinct metabolic phenotypes. Loss of genes that drive endodermal lineage specification, HNF4A and GATA6, switch metabolic profiles from classical (pancreatic) to predominantly squamous, with glycogen synthase kinase 3 beta (GSK3β) a key regulator of glycolysis. Pharmacological inhibition of GSK3β results in selective sensitivity in the squamous subtype; however, a subset of these squamous patient-derived cell lines (PDCLs) acquires rapid drug tolerance. Using chromatin accessibility maps, we demonstrate that the squamous subtype can be further classified using chromatin accessibility to predict responsiveness and tolerance to GSK3β inhibitors. Our findings demonstrate that distinct patterns of chromatin accessibility can be used to identify patient subgroups that are indistinguishable by gene expression profiles, highlighting the utility of chromatin-based biomarkers for patient selection in the treatment of PDAC.

The Kaipara Harbour in New Zealand is one of the largest estuarine systems in the world, containing significant areas of subtidal seagrass habitat (Zostera muelleri). Light availability at the maximum depth limit for Z. muelleri was measured at 2.10 (0.19 SEM) and 4.91 (0.53 SEM) mol photons m−2 d−1 during the winter and summer monitoring periods, respectively. The primary drivers of benthic light availability were found to be surface light availability, the timing of the low tide and water clarity. Core sampling analysis suggested that biomass of seagrass growing at the maximum depth limit was low, indicative of light limitation. The results of this study suggest that the subtidal distribution of seagrass in the Kaipara Harbour is light-limited and that reductions in water clarity due to changes in land use are likely to result in significant reductions in the extent and productivity of subtidal seagrass habitat.

In this self-contained paper we prove that Voevodsky's smooth blowup triangle of motives generalises to a smooth blowup triangle of motives with modulus.

microRNA engineering of CHO cells has already proved successful in enhancing various industrially relevant phenotypes and producing various recombinant products. A single miRNA's ability to interact with multiple mRNA targets allows their regulatory capacity to extend to processes such as cellular metabolism. Various metabolic states have previously been associated with particular CHO cell phenotypes such as glycolytic or oxidative metabolism accommodating growth and productivity, respectively. miR-23 has previously been demonstrated to play a role in glutamate metabolism resulting in enhanced oxidative phosphorylation through the TCA cycle. Re-programming cellular bioenergetics through miR-23 could tip the balance, forcing mammalian production cells to be more productive by favoring metabolic channelling into oxidative metabolism. CHO clones depleted of miR-23 using a miR-sponge decoy demonstrated an average ∼three-fold enhanced specific productivity with no impact on cell growth. Using a cell respirometer, mitochondrial activity was found to be enhanced by ∼30% at Complex I and II of the electron transport system. Additionally, label-free proteomic analysis uncovered various potential novel targets of miR-23 including LE1 and IDH1, both implicated in oxidative metabolism and mitochondrial activity. These results demonstrate miRNA-based engineering as a route to re-programming cellular metabolism resulting in increased productivity, without affecting growth.

Paraneoplastic pemphigus (PNP) is an autoimmune mucocutaneous blistering disease driven by autoantibodies against plakins expressed in mucosal epithelium. Diagnosis can be difficult as both clinical and biopsy features overlap with other blistering disorders, thus serology is important. Indirect immunofluorescence (IIF) on rat bladder substrate is the most widely used assay, but plakin-specific autoantibody assays have recently become available.The aim of this study was to compare the performance of five PNP assays in patients with mucosal blistering disease: IIF with rat bladder, monkey bladder and rat cardiac substrates, an envoplakin enzyme-linked immunosorbent assay (ELISA), and an envoplakin-transfected HEK cell based assay (CBA).Fifty-one patient serum samples, comprising three PNP patients and 48 disease controls, were collected along with 10 healthy control samples, and analysed using the five assays.IIF on rat and monkey bladder substrates both showed high specificity (97% and 95%, respectively), and correctly identified all three PNP sera. The envoplakin ELISA was equally specific (98%) but identified only one PNP patient. The CBA was difficult to interpret, and both this assay and IIF on rat cardiac substrate lacked specificity (82% and 83%, respectively).In this study IIF using either rat or monkey bladder substrates performed strongly, whilst the envoplakin ELISA seemed to lack sensitivity, and the CBA and IIF on rat cardiac substrate were inferior. Our findings suggest that traditional IIF-based assays remain the preferred approach in the serological diagnosis of PNP.

Identification of protein targets that play a role in breast cancer invasion may help to understand the rapid progression of cancer and may lead to the development of new biomarkers for the disease. In this study, we compared two highly invasive and two poorly invasive breast cancer cell lines using comparative label-free LC-MS profiling in order to identify differentially expressed proteins that may be linked to the invasive phenotype in vitro. Forty-five proteins were found to be upregulated, and 34 proteins, downregulated. UV excision repair protein RAD23 homologue B (RAD23B) was found among the downregulated proteins in highly invasive breast cancer cell lines. In poorly invasive breast cancer cell lines, siRNA-mediated downregulation of RAD23B subsequently led to an increase in invasion and adhesion in vitro. Immunohistochemistry analysis of 164 specimens of invasive breast cancer showed that having a high percentage (>80%) of RAD23B positive nuclei was significantly associated with histopathological grades 1 and 2 breast cancer and with low mitotic activity. In addition, a high staining intensity for RAD23B in the cytoplasm was significantly associated with histopathological grade 3 breast cancer. This study suggests a potential role of RAD23B in breast cancer progression and may further imply a tumor suppressor role of nuclear RAD23B in breast cancer.

We review the contributions from research conducted through the Leigh Marine Laboratory (LML) since its establishment in 1962, to the understanding of the biology and ecology of the rock lobster, Jasus edwardsii. The number of publications (103 since 1978), their breadth of subject matter, and their frequency of citation indicate the influence of this research effort. The development of an underwater population sampling tool at the LML has been key to the research on lobster distribution, abundance, size structure and sex ratios. These, in turn, allowed significant insights into the impact of fishing on lobster populations, population recovery in marine reserves, the mating system of lobsters, and the cascading effects of lobster removal on reef communities. Other key research has focused on the planktonic larval and post-larval stages. It is likely that J. edwardsii has received a greater level of ecological research effort through the LML than any other species. The location of the LML on a str...

Let S be an essentially smooth scheme over a field and l a prime number invertible on S. We show that the algebra of bistable operations in the mod l motivic cohomology of smooth S-schemes is generated by the motivic Steenrod operations. This was previously proved by Voevodsky for S a field of characteristic zero. We follow Voevodsky's proof but remove its dependence on characteristic zero by using \'etale cohomology instead of topological realization and by replacing resolution of singularities with a theorem of Gabber on alterations., Comment: 39 pages

Flexibility is an important physical quality. Self-myofascial release (SMFR) methods such as foam rolling (FR) increase flexibility acutely but how long such increases in range of motion (ROM) last is unclear. Static stretching (SS) also increases flexibility acutely and produces a cross-over effect to contralateral limbs. FR may also produce a cross-over effect to contralateral limbs but this has not yet been identified.To explore the potential cross-over effect of SMFR by investigating the effects of a FR treatment on the ipsilateral limb of 3 bouts of 30 seconds on changes in ipsilateral and contralateral ankle DF ROM and to assess the time-course of those effects up to 20 minutes post-treatment.A within- and between-subject design was carried out in a convenience sample of 26 subjects, allocated into FR (n=13) and control (CON, n=13) groups. Ankle DF ROM was recorded at baseline with the in-line weight-bearing lunge test for both ipsilateral and contralateral legs and at 0, 5, 10, 15, 20 minutes following either a two-minute seated rest (CON) or 3 3 30 seconds of FR of the plantar flexors of the dominant leg (FR). Repeated measures ANOVA was used to examine differences in ankle DF ROM.No significant between-group effect was seen following the intervention. However, a significant within-group effect (p0.05) in the FR group was seen between baseline and all post-treatment time-points (0, 5, 10, 15 and 20 minutes). Significant within-group effects (p0.05) were also seen in the ipsilateral leg between baseline and at all post-treatment time-points, and in the contralateral leg up to 10 minutes post-treatment, indicating the presence of a cross-over effect.FR improves ankle DF ROM for at least 20 minutes in the ipsilateral limb and up to 10 minutes in the contralateral limb, indicating that FR produces a cross-over effect into the contralateral limb. The mechanism producing these cross-over effects is unclear but may involve increased stretch tolerance, as observed following SS.2c.