A physically based parameterization of gravity drainage for sea-ice modeling

We incorporate a physically derived parameterization of gravity drainage, in terms of a convective upwelling velocity, into a one-dimensional, thermodynamic sea- ice model of the kind currently used in coupled climate models. Our parameterization uses a local Rayleigh number to represent the important feedback between ice salinity, porosity, permeability and desalination rate. It allows us to determine salt fluxes from sea ice and the corresponding evolution of the bulk salinity of the ice, in contrast to older, established models that prescribe the ice salinity. This improves the predictive power of climate models in terms of buoyancy fluxes to the polar oceans, and also the thermal properties of sea ice, which depend on its salinity. We analyze the behaviour of exist- ing fixed-salinity models, elucidate the physics by which changing salinity affects ice growth and compare against our dynamic-salinity model, both in terms of laboratory experiments and also deep-ocean calculations. These comparisons explain why the direct effect of ice salinity on growth is relatively small (though not always negligible, and sometimes dif- ferent from previous studies), and also highlight substantial differences in the qualita- tive pattern and quantitative magnitude of salt fluxes into the polar oceans. Our study is particularly relevant to growing first-year ice, when gravity drainage is the dominant mechanism by which ice desalinates. We expect that our dynamic model, which respects the underlying physics of brine drainage, should be more robust to changes in polar cli- mate and more responsive to rapid changes in oceanic and atmospheric forcing.This is the accepted manuscript. The final version is available from Wiley/American Geophysical Union at http://onlinelibrary.wiley.com/doi/10.1002/2013JC009296/abstract

HAGE, a cancer/testis antigen expressed at the protein level in a variety of cancers

The search for novel tumour antigens that are either uniquely expressed or over-expressed in a wide variety of tumours is still ongoing. Because of their expression in a broad spectrum of cancers and limited expression in normal tissues, cancer/testis antigens are considered to be potentially reliable targets for immunotherapy of cancer in general. The helicase antigen HAGE has been identified as a cancer/testis antigen. However, little is known about its expression in normal and cancer tissues. Using a newly developed antibody against HAGE, specific staining of its expression by immunohistochemistry was validated and optimised on murine tumours transfected to express the HAGE protein. The antibody was subsequently used to determine HAGE expression in normal human and cancer tissue microarrays. HAGE protein expression was confirmed in 75% (12/16) of carcinomas as compared to normal tissues, which either did not express HAGE at all or expressed HAGE at very low levels with the exception of testis. Interestingly, discrepancies were also found between mRNA analysis by real time quantitative PCR (RT-qPCR) and protein analysis by immunohistochemistry, emphasising the need to validate the expression of cancer/testis antigens at the protein level prior to the development of new vaccine strategies. HAGE is therefore proposed to be a valid candidate for designing a broad spectrum vaccine against cancer

Sea-ice thermodynamics and brine drainage

Significant changes in the state of the Arctic ice cover are occurring. As the summertime extent of sea ice diminishes, the Arctic is increasingly characterized by first-year rather than multi-year ice. It is during the early stages of ice growth that most brine is injected into the oceans, contributing to the buoyancy flux that mediates the thermo-haline circulation. Current operational sea-ice components of climate models often treat brine rejection between sea ice and the ocean similarly to a thermodynamic segregation process, assigning a fixed salinity to the sea ice, typical of multi-year ice. However, brine rejection is a dynamical, buoyancy-driven process and the salinity of sea ice varies significantly during the first growth season. As a result, current operational models may over predict the early brine fluxes from newly formed sea ice, which may have consequences for coupled simulations of the polar oceans. Improvements both in computational power and our understanding of the processes involved have led to the emergence of a new class of sea-ice models that treat brine rejection dynamically and should enhance predictions of the buoyancy forcing of the oceans

Protection afforded by heat shock protein 60 from Francisella tularensis is due to copurified lipopolysaccharide.

Heat shock proteins (Hsps) have attracted significant attention as protective antigens against a range of diseases caused by bacterial pathogens. However, more recently there have been suggestions that the protective response is due to the presence of peptide components other than Hsps. We have shown that mice that had been immunized with purified heat shock protein 60 (Hsp60) isolated from Francisella tularensis were protected against a subsequent challenge with some strains of the bacterium. However, this protection appeared to be due to trace amounts of lipopolysaccharide, which were too low to be detected by using the Limulus amoebocyte lysate assay. This finding raises the possibility that the protection afforded by other bacterial Hsp60 proteins may be due to trace quantities of polysaccharide antigens carried by and acting in conjunction with the Hsps

A diagnostic conundrum

A 26-year-old man was referred with facial weakness, dysarthria, dysphagia, ophthalmoparesis and severely weak and wasted legs. His symptoms had begun when aged 20 with electric shock pains and paraesthesia in both feet progressing over 6 months to the lower calves. He then developed buttock numbness and occasional faecal incontinence. By age 22, he had diffuse lower limb weakness and wasting, with difficulty standing from a seated position and frequent tripping. He became wheelchair-dependent within 3 years

Salt marshes create more extensive channel networks than mangroves.

This is the final version. Available from Nature Research via the DOI in this record. Data availability: The data generated in this study have been deposited in the Zenodo database under accession code (https://doi.org/10.5281/zenodo.6331067).Coastal wetlands fulfil important functions for biodiversity conservation and coastal protection, which are inextricably linked to typical morphological features like tidal channels. Channel network configurations in turn are shaped by bio-geomorphological feedbacks between vegetation, hydrodynamics and sediment transport. This study investigates the impact of two starkly different recruitment strategies between mangroves (fast/homogenous) and salt marshes (slow/patchy) on channel network properties. We first compare channel networks found in salt marshes and mangroves around the world and then demonstrate how observed channel patterns can be explained by vegetation establishment strategies using controlled experimental conditions. We find that salt marshes are dissected by more extensive channel networks and have shorter over-marsh flow paths than mangrove systems, while their branching patterns remain similar. This finding is supported by our laboratory experiments, which reveal that different recruitment strategies of mangroves and salt marshes hamper or facilitate channel development, respectively. Insights of our study are crucial to understand wetland resilience with rising sea-levels especially under climate-driven ecotone shifts

HAGE (DDX43) is a biomarker for poor prognosis and a predictor of chemotherapy response in breast cancer

Background: HAGE protein is a known immunogenic cancer-specific antigen. Methods: The biological, prognostic and predictive values of HAGE expression was studied using immunohistochemistry in three cohorts of patients with BC (n=2147): early primary (EP-BC; n=1676); primary oestrogen receptor-negative (PER-BC; n=275) treated with adjuvant anthracycline-combination therapies (Adjuvant-ACT); and primary locally advanced disease (PLA-BC) who received neo-adjuvant anthracycline-combination therapies (Neo-adjuvant-ACT; n=196). The relationship between HAGE expression and the tumour-infiltrating lymphocytes (TILs) in matched prechemotherapy and postchemotherapy samples were investigated. Results: Eight percent of patients with EP-BC exhibited high HAGE expression (HAGEþ) and was associated with aggressive clinico-pathological features (Ps<0.01). Furthermore, HAGEþexpression was associated with poor prognosis in both univariate and multivariate analysis (Ps<0.001). Patients with HAGE+ did not benefit from hormonal therapy in high-risk ER-positive disease. HAGE+ and TILs were found to be independent predictors for pathological complete response to neoadjuvant-ACT; P<0.001. A statistically significant loss of HAGE expression following neoadjuvant-ACT was found (P=0.000001), and progression-free survival was worse in those patients who had HAGE+ residual disease (P=0.0003). Conclusions: This is the first report to show HAGE to be a potential prognostic marker and a predictor of response to ACT in patients with BC

Development of a core information set for colorectal cancer surgery: a consensus study

Objective ‘Core information sets’ (CISs) represent baseline information, agreed by patients and professionals, to stimulate individualised patient-centred discussions. This study developed a CIS for use before colorectal cancer (CRC) surgery. Design Three phase consensus study: (1) Systematic literature reviews and patient interviews to identify potential information of importance to patients, (2) UK national Delphi survey of patients and professionals to rate the importance of the information, (3) international consensus meeting to agree on the final CIS. Setting UK CRC centres. Participants Purposive sampling was conducted to ensure CRC centre representation based upon geographical region and caseload volume. Responses were received from 63/81 (78%) centres (90 professionals). Adult patients who had undergone CRC surgery were eligible, and purposive sampling was conducted to ensure representation based on age, sex and cancer location (rectum, left and right colon). Responses were received from 97/267 (35%) patients with a wide age range (29–87), equal sex ratio and cancer location. Attendees of the international Tripartite Colorectal Conference were eligible for the consensus meeting. Outcomes Phase 1: Information of potential importance to patients was extracted verbatim and operationalised into a Delphi questionnaire. Phase 2: Patients and professionals rated the importance information on a 9-point Likert scale, and resurveyed following group feedback. Information rated of low importance were discarded using predefined criteria. Phase 3: A modified nominal group technique was used to gain final consensus in separate consensus meetings with patients and professionals. Results Data sources identified 1216 pieces of information that informed a 98-item questionnaire. Analysis led to 50 and 23 information domains being retained after the first and second surveys, respectively. The final CIS included 11 concepts including specific surgical complications, short and long-term survival, disease recurrence, stoma and quality of life issues. Conclusions This study has established a CIS for professionals to discuss with patients before CRC surgery

Synthesis and summary of patient-reported outcome measures to inform the development of a core outcome set in colorectal cancer surgery

AIM: Patient-reported outcome (PRO) measures (PROMs) are standard measures in the assessment of colorectal cancer (CRC) treatment, but the range and complexity of available PROMs may be hindering the synthesis of evidence. This systematic review aimed to: (i) summarize PROMs in studies of CRC surgery and (ii) categorize PRO content to inform the future development of an agreed minimum 'core' outcome set to be measured in all trials. METHOD: All PROMs were identified from a systematic review of prospective CRC surgical studies. The type and frequency of PROMs in each study were summarized, and the number of items documented. All items were extracted and independently categorized by content by two researchers into 'health domains', and discrepancies were discussed with a patient and expert. Domain popularity and the distribution of items were summarized. RESULTS: Fifty-eight different PROMs were identified from the 104 included studies. There were 23 generic, four cancer-specific, 11 disease-specific and 16 symptom-specific questionnaires, and three ad hoc measures. The most frequently used PROM was the EORTC QLQ-C30 (50 studies), and most PROMs (n = 40, 69%) were used in only one study. Detailed examination of the 50 available measures identified 917 items, which were categorized into 51 domains. The domains comprising the most items were 'anxiety' (n = 85, 9.2%), 'fatigue' (n = 67, 7.3%) and 'physical function' (n = 63, 6.9%). No domains were included in all PROMs. CONCLUSION: There is major heterogeneity of PRO measurement and a wide variation in content assessed in the PROMs available for CRC. A core outcome set will improve PRO outcome measurement and reporting in CRC trials

Lepton Acceleration in Pulsar Wind Nebulae

Pulsar Wind Nebulae (PWNe) act as calorimeters for the relativistic pair winds emanating from within the pulsar light cylinder. Their radiative dissipation in various wavebands is significantly different from that of their pulsar central engines: the broadband spectra of PWNe possess characteristics distinct from those of pulsars, thereby demanding a site of lepton acceleration remote from the pulsar magnetosphere. A principal candidate for this locale is the pulsar wind termination shock, a putatively highly-oblique, ultra-relativistic MHD discontinuity. This paper summarizes key characteristics of relativistic shock acceleration germane to PWNe, using predominantly Monte Carlo simulation techniques that compare well with semi-analytic solutions of the diffusion-convection equation. The array of potential spectral indices for the pair distribution function is explored, defining how these depend critically on the parameters of the turbulent plasma in the shock environs. Injection efficiencies into the acceleration process are also addressed. Informative constraints on the frequency of particle scattering and the level of field turbulence are identified using the multiwavelength observations of selected PWNe. These suggest that the termination shock can be comfortably invoked as a principal injector of energetic leptons into PWNe without resorting to unrealistic properties for the shock layer turbulence or MHD structure.Comment: 19 pages, 5 figures, invited review to appear in Proc. of the inaugural ICREA Workshop on "The High-Energy Emission from Pulsars and their Systems" (2010), eds. N. Rea and D. Torres, (Springer Astrophysics and Space Science series