The WISDOM Radar: Unveiling the Subsurface Beneath the ExoMars Rover and Identifying the Best Locations for Drilling

The search for evidence of past or present life on Mars is the principal objective of the 2020 ESA-Roscosmos ExoMars Rover mission. If such evidence is to be found anywhere, it will most likely be in the subsurface, where organic molecules are shielded from the destructive effects of ionizing radiation and atmospheric oxidants. For this reason, the ExoMars Rover mission has been optimized to investigate the subsurface to identify, understand, and sample those locations where conditions for the preservation of evidence of past life are most likely to be found. The Water Ice Subsurface Deposit Observation on Mars (WISDOM) ground-penetrating radar has been designed to provide information about the nature of the shallow subsurface over depth ranging from 3 to 10 m (with a vertical resolution of up to 3 cm), depending on the dielectric properties of the regolith. This depth range is critical to understanding the geologic evolution stratigraphy and distribution and state of subsurface H2O, which provide important clues in the search for life and the identification of optimal drilling sites for investigation and sampling by the Rover's 2-m drill. WISDOM will help ensure the safety and success of drilling operations by identification of potential hazards that might interfere with retrieval of subsurface samples

The low-lying excitations of polydiacetylene

The Pariser-Parr-Pople Hamiltonian is used to calculate and identify the nature of the low-lying vertical transition energies of polydiacetylene. The model is solved using the density matrix renormalisation group method for a fixed acetylenic geometry for chains of up to 102 atoms. The non-linear optical properties of polydiacetylene are considered, which are determined by the third-order susceptibility. The experimental 1Bu data of Giesa and Schultz are used as the geometric model for the calculation. For short chains, the calculated E(1Bu) agrees with the experimental value, within solvation effects (ca. 0.3 eV). The charge gap is used to characterise bound and unbound states. The nBu is above the charge gap and hence a continuum state; the 1Bu, 2Ag and mAg are not and hence are bound excitons. For large chain lengths, the nBu tends towards the charge gap as expected, strongly suggesting that the nBu is the conduction band edge. The conduction band edge for PDA is agreed in the literature to be ca. 3.0 eV. Accounting for the strong polarisation effects of the medium and polaron formation gives our calculated E(nBu) ca. 3.6 eV, with an exciton binding energy of ca. 1.0 eV. The 2Ag state is found to be above the 1Bu, which does not agree with relaxed transition experimental data. However, this could be resolved by including explicit lattice relaxation in the Pariser- Parr-Pople-Peierls model. Particle-hole separation data further suggest that the 1Bu, 2Ag and mAg are bound excitons, and that the nBu is an unbound exciton.Comment: LaTeX, 23 pages, 4 postscript tables and 8 postscript figure

Contribution of plasma cells and B cells to hidradenitis suppurativa pathogenesis

Hidradenitis suppurativa (HS) is a debilitating chronic inflammatory skin disease characterized by chronic abscess formation and development of multiple draining sinus tracts in the groin, axillae, and perineum. Using proteomic and transcriptomic approaches, we characterized the inflammatory responses in HS in depth, revealing immune responses centered on IFN-γ, IL-36, and TNF, with lesser contribution from IL-17A. We further identified B cells and plasma cells, with associated increases in immunoglobulin production and complement activation, as pivotal players in HS pathogenesis, with Bruton’s tyrosine kinase (BTK) and spleen tyrosine kinase (SYK) pathway activation as a central signal transduction network in HS. These data provide preclinical evidence to accelerate the path toward clinical trials targeting BTK and SYK signaling in moderate-to-severe HS

Age at first birth in women is genetically associated with increased risk of schizophrenia

Prof. Paunio on PGC:n jäsenPrevious studies have shown an increased risk for mental health problems in children born to both younger and older parents compared to children of average-aged parents. We previously used a novel design to reveal a latent mechanism of genetic association between schizophrenia and age at first birth in women (AFB). Here, we use independent data from the UK Biobank (N = 38,892) to replicate the finding of an association between predicted genetic risk of schizophrenia and AFB in women, and to estimate the genetic correlation between schizophrenia and AFB in women stratified into younger and older groups. We find evidence for an association between predicted genetic risk of schizophrenia and AFB in women (P-value = 1.12E-05), and we show genetic heterogeneity between younger and older AFB groups (P-value = 3.45E-03). The genetic correlation between schizophrenia and AFB in the younger AFB group is -0.16 (SE = 0.04) while that between schizophrenia and AFB in the older AFB group is 0.14 (SE = 0.08). Our results suggest that early, and perhaps also late, age at first birth in women is associated with increased genetic risk for schizophrenia in the UK Biobank sample. These findings contribute new insights into factors contributing to the complex bio-social risk architecture underpinning the association between parental age and offspring mental health.Peer reviewe

Effects of a high-dose 24-h infusion of tranexamic acid on death and thromboembolic events in patients with acute gastrointestinal bleeding (HALT-IT): an international randomised, double-blind, placebo-controlled trial

Background: Tranexamic acid reduces surgical bleeding and reduces death due to bleeding in patients with trauma. Meta-analyses of small trials show that tranexamic acid might decrease deaths from gastrointestinal bleeding. We aimed to assess the effects of tranexamic acid in patients with gastrointestinal bleeding. Methods: We did an international, multicentre, randomised, placebo-controlled trial in 164 hospitals in 15 countries. Patients were enrolled if the responsible clinician was uncertain whether to use tranexamic acid, were aged above the minimum age considered an adult in their country (either aged 16 years and older or aged 18 years and older), and had significant (defined as at risk of bleeding to death) upper or lower gastrointestinal bleeding. Patients were randomly assigned by selection of a numbered treatment pack from a box containing eight packs that were identical apart from the pack number. Patients received either a loading dose of 1 g tranexamic acid, which was added to 100 mL infusion bag of 0·9% sodium chloride and infused by slow intravenous injection over 10 min, followed by a maintenance dose of 3 g tranexamic acid added to 1 L of any isotonic intravenous solution and infused at 125 mg/h for 24 h, or placebo (sodium chloride 0·9%). Patients, caregivers, and those assessing outcomes were masked to allocation. The primary outcome was death due to bleeding within 5 days of randomisation; analysis excluded patients who received neither dose of the allocated treatment and those for whom outcome data on death were unavailable. This trial was registered with Current Controlled Trials, ISRCTN11225767, and ClinicalTrials.gov, NCT01658124. Findings: Between July 4, 2013, and June 21, 2019, we randomly allocated 12 009 patients to receive tranexamic acid (5994, 49·9%) or matching placebo (6015, 50·1%), of whom 11 952 (99·5%) received the first dose of the allocated treatment. Death due to bleeding within 5 days of randomisation occurred in 222 (4%) of 5956 patients in the tranexamic acid group and in 226 (4%) of 5981 patients in the placebo group (risk ratio [RR] 0·99, 95% CI 0·82–1·18). Arterial thromboembolic events (myocardial infarction or stroke) were similar in the tranexamic acid group and placebo group (42 [0·7%] of 5952 vs 46 [0·8%] of 5977; 0·92; 0·60 to 1·39). Venous thromboembolic events (deep vein thrombosis or pulmonary embolism) were higher in tranexamic acid group than in the placebo group (48 [0·8%] of 5952 vs 26 [0·4%] of 5977; RR 1·85; 95% CI 1·15 to 2·98). Interpretation: We found that tranexamic acid did not reduce death from gastrointestinal bleeding. On the basis of our results, tranexamic acid should not be used for the treatment of gastrointestinal bleeding outside the context of a randomised trial

The global retinoblastoma outcome study : a prospective, cluster-based analysis of 4064 patients from 149 countries

DATA SHARING : The study data will become available online once all analyses are complete.BACKGROUND : Retinoblastoma is the most common intraocular cancer worldwide. There is some evidence to suggest that major differences exist in treatment outcomes for children with retinoblastoma from different regions, but these differences have not been assessed on a global scale. We aimed to report 3-year outcomes for children with retinoblastoma globally and to investigate factors associated with survival. METHODS : We did a prospective cluster-based analysis of treatment-naive patients with retinoblastoma who were diagnosed between Jan 1, 2017, and Dec 31, 2017, then treated and followed up for 3 years. Patients were recruited from 260 specialised treatment centres worldwide. Data were obtained from participating centres on primary and additional treatments, duration of follow-up, metastasis, eye globe salvage, and survival outcome. We analysed time to death and time to enucleation with Cox regression models. FINDINGS : The cohort included 4064 children from 149 countries. The median age at diagnosis was 23·2 months (IQR 11·0–36·5). Extraocular tumour spread (cT4 of the cTNMH classification) at diagnosis was reported in five (0·8%) of 636 children from high-income countries, 55 (5·4%) of 1027 children from upper-middle-income countries, 342 (19·7%) of 1738 children from lower-middle-income countries, and 196 (42·9%) of 457 children from low-income countries. Enucleation surgery was available for all children and intravenous chemotherapy was available for 4014 (98·8%) of 4064 children. The 3-year survival rate was 99·5% (95% CI 98·8–100·0) for children from high-income countries, 91·2% (89·5–93·0) for children from upper-middle-income countries, 80·3% (78·3–82·3) for children from lower-middle-income countries, and 57·3% (52·1-63·0) for children from low-income countries. On analysis, independent factors for worse survival were residence in low-income countries compared to high-income countries (hazard ratio 16·67; 95% CI 4·76–50·00), cT4 advanced tumour compared to cT1 (8·98; 4·44–18·18), and older age at diagnosis in children up to 3 years (1·38 per year; 1·23–1·56). For children aged 3–7 years, the mortality risk decreased slightly (p=0·0104 for the change in slope). INTERPRETATION : This study, estimated to include approximately half of all new retinoblastoma cases worldwide in 2017, shows profound inequity in survival of children depending on the national income level of their country of residence. In high-income countries, death from retinoblastoma is rare, whereas in low-income countries estimated 3-year survival is just over 50%. Although essential treatments are available in nearly all countries, early diagnosis and treatment in low-income countries are key to improving survival outcomes.The Queen Elizabeth Diamond Jubilee Trust and the Wellcome Trust.https://www.thelancet.com/journals/langlo/homeam2023Paediatrics and Child Healt

Supraspinal involvement in acupuncture analgesia

Electroacupuncture (EA) on Zusanli (st. 36) and Shangjuxu (st. 38) (10 Hz, 1.0 ms) was found to produce a long-lasting inhibition of wide dynamic range neurones in the dorsal horn of the spinal cord and to prolong the latency of the tail-flick reflex in the lightly anaesthetized rat. This inhibition was effectively produced at a stimulation intensity which excited only A13 fibres. The effects of EA were eliminated by cold-blocking the spinal cord rostral to the recording site suggesting a supraspinal involvement in the EA-induced inhibition of spinal cord nociceptive transmission. EA also facilitated the discharge of non-clock-like dorsal raphe neurones (NCL). Bilateral lesions of the ventrolateral tract (VLT), but not the dorsolateral funiculi (DLF), blocked this effect suggesting that the ascending arm of the loop is via the VLT. The descending arm is located in the DLF since bilateral lesions of the DLF blocked the effects of EA in the spinal cord. Evidence in the literature suggests that the dorsal raphe nucleus (DRN) may be involved in the above supraspinal loop as well as in an ascending inhibitory pathway to the nucleus parafascicularis (NPF). Examination of the DRN revealed three types of neurones: clock-like (CL), NCL and non-clock-like non-responding neurones (NCLN). The NCL neurones were excited by noxious and non-noxious natural peripheral stimuli as well as EA. The other neurones were non-responsive to these stimuli. NCL neurones of the DRN were also antidromically activated by 11 NPF stimulation indicating that the projection from the DRN to the NPF is direct. Stimulation of the DRN produced an inhibition of NPF neurones with sudden onset and offset and a duration correlated with the length of stimulation. EA also produced long-lasting inhibition of these cells. The inhibitory pathway from the DRN to the NPF, which is activated by EA and presumably mediated by NCL neurones, would appear to be serotonergic. The evidence for this is that the inhibition evoked by DRN stimulation or EA is enhanced by alaproclate, a 5-FIT uptake blocker, and blocked by 5,7-DHT, a 5-HT neurotoxic agent, or cyproheptadine, a serotonin antagonist.Medicine, Faculty ofGraduat

Thermal effects on the optical spectra of a polydiacetylene: Poly{1,2-bis [4-(isopropylcarbamoyloxy) -\u3ci\u3en\u3c/i\u3e-butyl]-1-buten-3-ynylene}

The reflection spectra of single crystals of the polydiacetylene, IPUDO [R= (CH2)4OCONHCH (CH3)2], were measured between 25° C and 160° C. A nearly reversible thermochromic change is observed together with a variation of hysteresis upon cycling. The latter is attributed to annealing that permits the pendant groups to adopt a conformation which favors the butatriene-type configuration of the polymer at high temperatures. Intensities of the high and low temperature spectra obtained by Kramers–Kronig transforms are in excellent agreement with the spectral intensities of polydiacetylenes which are prototypes for the two configurations

Improvement of Safety in Operating Theatres by Training and Teamwork

Medical incidents in public hospitals in Hong Kong have persisted for years. The operating theatres are one of the places where medical accidents occur, especially affecting service quality. The surgical team is a substantial cause of medical incidents, possibly because of human mistakes, environmental, equipment, and system failures. Not all surgery departments will implement uniform working styles. The Hospital Authority may set a management plan to unify practice and to identity the problems faced. Therefore, the government and Hospital Authority should focus on human resources, especially in terms of professional training and retention of staff. After all, surgery is a task of teamwork

Overview of Palliative Care Service in Hong Kong

Palliative care service is a growing trend for patients with terminal illnesses. The purpose of palliative care is to improve the quality of life for the patients and their family by providing comprehensive care such as symptoms control, pain relief and counselling support. More and more people prefer to spend the final stage of their life in a comfortable environment with adequate care. However, Hong Kong is only ranked 22 in 2015 Quality of Death Index, and hence enhancement of palliative care service is much needed. This review paper aims to evaluate the current resources and development of palliative care service in Hong Kong and suggest improvement of the service. This study reveals that the system in Hong Kong lacks a comprehensive policy, thus limiting organisations to provide the service to small-scale operations and resulting in fragmentation of the co-operation between the public and private sectors. Factors such as professional training, community engagement, culture and financial issues are affecting the development and adequacy of palliative care service.&nbsp