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Introduction Central venous access devices (CVADs) are commonly used for the treatment of paediatric cancer patients. Catheter locking is a routine intervention that prevents CVAD-associated adverse events, such as infection, occlusion and thrombosis. While laboratory and clinical data are promising, tetra-EDTA (T-EDTA) has yet to be rigorously evaluated or introduced in cancer care as a catheter lock.Methods and analysis This is a protocol for a two-arm, superiority type 1 hybrid effectiveness-implementation randomised controlled trial conducted at seven hospitals across Australia and New Zealand. Randomisation will be in a 3:2 ratio between the saline (heparinised saline and normal saline) and T-EDTA groups, with randomly varied blocks of size 10 or 20 and stratification by (1) healthcare facility; (2) CVAD type and (3) duration of dwell since insertion. Within the saline group, there will be a random allocation between normal and heparin saline. Participants can be re-recruited and randomised on insertion of a new CVAD. Primary outcome for effectiveness will be a composite of CVAD-associated bloodstream infections (CABSI), CVAD-associated thrombosis or CVAD occlusion during CVAD dwell or at removal. Secondary outcomes will include CABSI, CVAD-associated-thrombosis, CVAD failure, incidental asymptomatic CVAD-associated-thrombosis, other adverse events, health-related quality of life, healthcare costs and mortality. To achieve 90% power (alpha=0.05) for the primary outcome, data from 720 recruitments are required. A mixed-methods approach will be employed to explore implementation contexts from the perspective of clinicians and healthcare purchasers.Ethics and dissemination Ethics approval has been provided by Children’s Health Queensland Hospital and Health Service Human Research Ethics Committee (HREC) (HREC/22/QCHQ/81744) and the University of Queensland HREC (2022/HE000196) with subsequent governance approval at all sites. Informed consent is required from the substitute decision-maker or legal guardian prior to participation. In addition, consent may also be obtained from mature minors, depending on the legislative requirements of the study site. The primary trial and substudies will be written by the investigators and published in peer-reviewed journals. The findings will also be disseminated through local health and clinical trial networks by investigators and presented at conferences.Trial registration number ACTRN12622000499785.

Purpose: The intramedullary interlocking device for metacarpophalangeal (MCP) joint arthrodesis (XMCP, Extremity Medical, Parsippany, NJ) has been shown to promote union at a precise angle, provide strong fixation without the need for prolonged immobilization, and lower the incidence of hardware irritation and revision surgery. In this study, we evaluated the clinical outcomes of patients undergoing MCP joint arthrodesis with the XMCP system using a retrospective chart review, patient reported outcomes, and radiographic analysis. Methods: A retrospective chart review and phone survey was conducted on 57 patients (58 cases) from a single institution between 2017 and 2022. The primary outcome was patient satisfaction, including pre- and postoperative Numeric Rating Scale (NRS) pain scores, Disabilities of Arm Shoulder and Hand (QuickDASH) outcomes, perceived grip strength, and willingness to undergo the procedure again. Secondary outcomes included the need for revision procedures, successful fusion of arthrodesis, and postoperative complications. Results: Of the 57 patients who underwent MCP joint arthrodesis of the thumb using the XMCP fusion device, a total of 43 (75%) completed the phone survey. The average age of patients was 67 years with an average clinical follow-up of 9 months (range 1–65 months). Patients who participated in the phone survey questionnaire had an average QuickDASH score of 24.7 ± 20.5. Average perceived NRS scores were 6.2 ± 3.5 and 1.2 ± 2.1 before and after surgery, respectively. Average perceived grip strength of patients was 3 ± 1.3 out of 5. When evaluating for concurrent procedures, there was no statistically significant difference in pre- or postoperative NRS scores. In total, 38 (88%) patients were satisfied with the procedure, and 39 (91%) patients would undergo the procedure again. Conclusion: Metacarpophalangeal joint arthrodesis of the thumb with the intramedullary fusion device is reproducible, allows for immediate use without immobilization, has a low number of complications, and provides improved function and pain relief. Level of Evidence: Therapeutic III.

To address safety and labour-intensive challenges in laser powder bed fusion, a novel Metal Additive Manufacturing using Powder Sheets (MAPS) method is employed. By examining the formation mechanism of the melt pool, we discovered that MAPS printing utilising a negative defocus strategy achieves a favourable conduction mode. This approach results in the fabrication of crack-free SS304 samples with over 99.65% relative density and elongated grains. These phenomena are caused by diverged laser power density distribution and decreased entrainment of byproducts such as vapour into the melt pool, as observed by the laser-powder sheet in-situ interaction. Furthermore, the productivity of MAPS increases when printing using the negative defocus setting compared to the scenario without defocus and productivity also increases with the decrease in scanning speed, attributed to a larger amount of metal particles entrained into the melt pool. This study provides insights into the novel MAPS manufacturing for functional metal components.

Data-driven computational analysis is becoming increasingly important in biomedical research, as the amount of data being generated continues to grow. However, the lack of practices of sharing research outputs, such as data, source code and methods, affects transparency and reproducibility of studies, which are critical to the advancement of science. Many published studies are not reproducible due to insufficient documentation, code, and data being shared. We conducted a comprehensive analysis of 453 manuscripts published between 2016–2021 and found that 50.1% of them fail to share the analytical code. Even among those that did disclose their code, a vast majority failed to offer additional research outputs, such as data. Furthermore, only one in ten articles organized their code in a structured and reproducible manner. We discovered a significant association between the presence of code availability statements and increased code availability. Additionally, a greater proportion of studies conducting secondary analyses were inclined to share their code compared to those conducting primary analyses. In light of our findings, we propose raising awareness of code sharing practices and taking immediate steps to enhance code availability to improve reproducibility in biomedical research. By increasing transparency and reproducibility, we can promote scientific rigor, encourage collaboration, and accelerate scientific discoveries. We must prioritize open science practices, including sharing code, data, and other research products, to ensure that biomedical research can be replicated and built upon by others in the scientific community.

The tissue diagnosis and staging of all types of lung cancer is foundational for prognosis and establishing the optimal treatment plan. In order to appropriately stage lung cancer, the highest stage should be established using the 8th edition TNM criteria, where tumor size (T), nodal involvement (N), and metastasis (M) are all taken into account. Establishing a tissue diagnosis may involve the use of CT guided biopsy, navigational bronchoscopy, endobronchial biopsy, endobronchial ultrasound, percutaneous lymph node biopsy and/or excisional biopsy of supraclavicular nodes. It is recommended to proceed with the method that is considered least invasive and provides the highest staging. We present a case of recurrent lung adenocarcinoma diagnosed with real time ultrasound-guided fine needle aspiration of a neck lymph node.

Abstract Background The Support and Treatment After Replacement (STAR) care pathway is a clinically important and cost-effective intervention found to improve pain outcomes over one year for people with chronic pain three months after total knee replacement (TKR). We followed up STAR trial participants to evaluate the longer-term clinical- and cost-effectiveness of this care pathway. Methods Participants who remained enrolled on the trial at one year were contacted by post at a median of four years after randomisation and invited to complete a questionnaire comprising the same outcomes collected during the trial. We captured pain (co-primary outcome using the Brief Pain Inventory (BPI) pain severity and interference scales; scored 0–10, best to worst), function, neuropathic characteristics, emotional aspects of pain, health-related quality of life, and satisfaction. Electronic hospital informatics data on hospital resource use for the period of one to four years post-randomisation were collected from participating hospital sites. The economic evaluation took an National Health Service (NHS) secondary care perspective, with a four-year time horizon. Results Overall, 226/337 (67%) of participants returned completed follow-up questionnaires, yielding adjusted between-group differences in BPI means of -0.42 (95% confidence interval, CI (-1.07, 0.23); p = 0.20) for pain severity and − 0.64 (95% CI -1.41, 0.12); p = 0.10) for pain interference. Analysis using a multiple imputed data set (n = 337) showed an incremental net monetary benefit in favour of the STAR care pathway of £3,525 (95% CI -£990 to £8,039) at a £20,000/QALY willingness-to-pay threshold, leading to a probability that the intervention was cost-effective of 0.94. Conclusions The magnitude of the longer-term benefits of the STAR care pathway are uncertain due to attrition of trial participants; however, there is a suggestion of some degree of sustained clinical benefit at four years. The care pathway remained cost-effective at four years. Trial registration ISRCTN: 92,545,361.

Introduction: Patients who are hospitalized may be at a higher risk for falling, which can result in additional injuries, longer hospitalizations, and extra cost for healthcare organizations. A frequent context for these falls is when a hospitalized patient needs to use the bathroom. While it is possible that “high-tech” tools like robots and AI applications can help, adopting a human-centered approach and engaging users and other affected stakeholders in the design process can help to maximize benefits and avoid unintended consequences.Methods: Here, we detail our findings from a human-centered design research effort to investigate how the process of toileting a patient can be ameliorated through the application of advanced tools like robots and AI. We engaged healthcare professionals in interviews, focus groups, and a co-creation session in order to recognize common barriers in the toileting process and find opportunities for improvement.Results: In our conversations with participants, who were primarily nurses, we learned that toileting is more than a nuisance for technology to remove through automation. Nurses seem keenly aware and responsive to the physical and emotional pains experienced by patients during the toileting process, and did not see technology as a feasible or welcomed substitute. Instead, nurses wanted tools which supported them in providing this care to their patients. Participants envisioned tools which helped them anticipate and understand patient toileting assistance needs so they could plan to assist at convenient times during their existing workflows. Participants also expressed favorability towards mechanical assistive features which were incorporated into existing equipment to ensure ubiquitous availability when needed without adding additional mass to an already cramped and awkward environment.Discussion: We discovered that the act of toileting served more than one function, and can be viewed as a valuable touchpoint in which nurses can assess, support, and encourage their patients to engage in their own recovery process as they perform a necessary and normal function of life. While we found opportunities for technology to make the process safer and less burdensome for patients and clinical staff alike, we believe that designers should preserve and enhance the therapeutic elements of the nurse-patient interaction rather than eliminate it through automation.

BackgroundThe survival for many children with relapsed/refractory cancers remains poor despite advances in therapies. Arginine metabolism plays a key role in the pathophysiology of a number of pediatric cancers. We report the first in child study of a recombinant human arginase, BCT-100, in children with relapsed/refractory hematological, solid or CNS cancers.ProcedurePARC was a single arm, Phase I/II, international, open label study. BCT-100 was given intravenously over one hour at weekly intervals. The Phase I section utilized a modified 3 + 3 design where escalation/de-escalation was based on both the safety profile and the complete depletion of arginine (defined as adequate arginine depletion; AAD

Introduction: The aim was to demonstrate the safety and tolerability of cannabidiol (CBD) with Δ9-THC in patients with moderate to severe chronic back or neck pain unresponsive to over-the-counter non-opioid analgesics. Methods: This was a non-randomized, single-arm, open-label study. Participants received escalating doses of an oromucosal-administered combination containing 10 mg/mL of Δ9-THC, 25 mg/mL of CBD. On day 1, patients received once-daily 0.5 mL Cybis® 10:25 (5 mg Δ9-THC plus 12.5 mg CBD daily), escalated at days 8, 15, and 22 to 0.5 mL twice-daily (bd) (10 mg Δ9-THC plus 25 mg CBD daily), 1.0 mL bd (20 mg Δ9-THC plus 50 mg CBD daily), and 1.5 mL bd (30 mg Δ9-THC plus 75 mg CBD daily), respectively. The primary outcome was safety and tolerability, with secondary objectives including pharmacokinetic and efficacy outcomes. Results: 28 patients were enrolled in the study. Their median age was 63.3 years, and half were female. The median history of neck/back pain was 10 years. The pharmacokinetics following single doses of 0.5 mL were variable; however, there were dose-dependent increases in trough levels of CBD and Δ9-THC. Cybis® 10:25 was well tolerated, with the majority of adverse events of mild severity. The most common adverse events were nausea, vomiting, fatigue, dizziness, headache, paresthesia, and anxiety. There were dose-dependent improvements in numerical pain rating scores (p < 0.001), with clinically significant reductions in pain at 1.0 mL bd and 1.5 mL bd doses (28.8% and 34.1% reductions, respectively, p < 0.001). Depressive symptoms and stress had dose-dependent reductions (p = 0.0182, p < 0.01, respectively). Conclusion: In patients with chronic neck/back pain, CBD and Δ9-THC are well tolerated and doses of 1.0 mL bd and 1.5 mL bd showed clinically significant reductions in pain compared to baseline pain scores.

Category: Midfoot/Forefoot; Diabetes Introduction/Purpose: Charcot arthropathy is a neurotraumatic foot disorder seen in patients with peripheral neuropathy. Surgical reconstruction via medial column arthrodesis with beams can restore plantigrade foot anatomy with decreased soft tissue dissection and improved bony compression. Methods: We identified 12 patients with midfoot (n=7) or hindfoot (n=5) Charcot who underwent medial column beaming arthrodesis between 2015 and 2021 b y one of two fellowship-trained foot and ankle surgeons at an academic medical center. Data collected from patient charts included demographics, medical history, complications, and reoperation rate. Meary’s angle was measured on lateral weightbearing radiographs preoperatively and up to two years postoperatively. Mean follow-up time was 2.50 (range, 1.04-6.98) years. Statistical analysis included correlation, two-tailed Student t-test, and Chi-squared test. Results: Meary’s angle was recorded preoperatively for 12 patients (19.3° ± 6.7°) and postoperatively at three months for 12 patients (4.0° ± 6.7°), at six months for 12 patients (7.1° ± 9.7°), at one year for 11 patients (6.1° ± 9.4°), and at two years for five patients (10.2° ± 6.4°). However, two (16.7%) patients showed a loss of deformity correction, which was demonstrated by a Meary’s angle that was greater at final follow-up than preoperatively. Overall complication, infection, reoperation rates were 50.0%, 41.7%, and 58.3%, respectively. Finally, dependent on preoperative ulceration, those with and without an ulcer did not differ in Meary’s angle at any time point, overall complication, infection, nor reoperation rate. Conclusion: Although the results showed a relatively high complication rate, the use of beaming arthrodesis was generally able to maintain a plantigrade foot and overall alignment, while decreasing the recurrence of plantar ulceration.

Abstract. Limb trauma remains the most prevalent survivable major combat injury. In the First World War, more than 700,000 British soldiers received limb wounds and more than 41,000 underwent an amputation, creating one of the largest amputee cohorts in history. Postamputation pain affects up to 85% of military amputees, suggesting that up to 33,000 British First World War veterans potentially reported postamputation pain. This qualitative systematic review explores the professional medical conversation around clinical management of chronic postamputation pain in this patient cohort, its development over the 20th century, and how this information was disseminated among medical professionals. We searched The Lancet and British Medical Journal archives (1914–1985) for reports referring to postamputation pain, its prevalence, mechanisms, descriptors, or clinical management. Participants were First World War veterans with a limb amputation, excluding civilians and veterans of all other conflicts. The search identified 9809 potentially relevant texts, of which 101 met the inclusion criteria. Reports emerged as early as 1914 and the discussion continued over the next 4 decades. Unexpected findings included early advocacy of multidisciplinary pain management, concerns over addiction, and the effect of chronic pain on mental health emerging decades earlier than previously thought. Chronic postamputation pain is still a significant issue for military rehabilitation. Similarities between injury patterns in the First World War and recent Iraq and Afghanistan conflicts mean that these historical aspects remain relevant to today's military personnel, clinicians, researchers, and policymakers.

Introduction Malignant pleural effusion (MPE) is common, with 50 000 new cases per year in the UK. MPE causes disabling breathlessness and indicates advanced disease with a poor prognosis. Treatment approaches focus on symptom relief and optimising quality of life (QoL). Patients who newly present with MPE commonly require procedural intervention for both diagnosis and therapeutic benefit.Thoracoscopic pleural biopsies are highly sensitive in diagnosing pleural malignancy. Talc poudrage may be delivered at thoracoscopy (TTP) to prevent effusion recurrence by effecting pleurodesis. Indwelling pleural catheters (IPCs) offer an alternative strategy for fluid control, enabling outpatient management and are often used as ‘rescue’ therapy following pleurodesis failure or in cases of ‘trapped lung’. It is unknown whether combining a TTP with IPC insertion will improve patient symptoms or reduce time spent in the hospital.The randomised thoracoscopic talc poudrage + indwelling pleural catheters versus thoracoscopic talc poudrage only in malignant pleural effusion trial (TACTIC) is the first randomised controlled trial (RCT) to examine the benefit of a combined TTP and IPC procedure, evaluating cost-effectiveness and patient-centred outcomes such as symptoms and QoL. The study remains in active recruitment and has the potential to radically transform the pathway for all patients presenting with MPE.Methods and analysis TACTIC is an unblinded, multicentre, RCT comparing the combination of TTP with an IPC to TTP alone. Co-primary outcomes are time spent in the hospital and mean breathlessness score over 4 weeks postprocedure. The study will recruit 124 patients and aims to define the optimal pathway for patients presenting with symptomatic MPE.Ethics and dissemination TACTIC is sponsored by North Bristol NHS Trust and has been granted ethical approval by the London-Brent Research Ethics Committee (REC ref: 21/LO/0495). Publication of results in a peer-reviewed journal and conference presentations are anticipated.Trial registration ISRCTN 11058680.

Objectives Describe the development of warm autoimmune hemolytic anemia warm (AIHA) secondary to a brown recluse spider (Loxosceles reclusa) bite is known as systemic loxoscelism; and review epidemiology, clinical manifestations, diagnostic work-up, pathophysiology, and treatment options associated with warm AIHA secondary to systemic loxoscelism.Methods Cases series of two cases of warm AIHA due to systemic loxoscelism and a review of the current literature: epidemiology, clinical manifestations, diagnostic work-up, pathophysiology, and treatment options associated with warm AIHA secondary to systemic loxoscelism.Results Presented here are two cases of warm AIHA due to systemic loxoscelism. Each patient was generally healthy appearing and presented with symptomatic anemia in the setting of brown recluse spider bites. Both patients were eventually found to have warm AIHA. Upon recognition of the diagnosis, the patients were started on corticosteroids and aggressive intravenous fluid hydration. In addition, they received transfusions of packed red blood cells. Their clinical courses improved, and they recovered to eventually be discharged home.Conclusion Envenomation by a brown recluse spider, Loxosceles reclusa, can result in systemic loxoscelism which can cause warm AIHA. The diagnosis of warm AIHA is confirmed by the direct antiglobulin/Coomb's test. Warm AIHA can be a life-threatening disease process. Hemodynamic support with intravenous fluids and RBC transfusion is the initial step in the management of these patients. Corticosteroids are the mainstay of current management. Second line treatments include rituximab. Rarely patients require splenectomy for refractory disease. Corticosteroids should be tapered over a three-month period.

NOTCH mutations are frequent in B cell malignancies. Here the authors use retroviral transduction of primary malignant B cells from Chronic Lymphocytic Leukemia (CLL) and Mantle Cell Lymphoma (MCL) patients to show that NOTCH1/2-mutations facilitate mechanism of immune escape.

Abstract Background Approximately 20% of people experience chronic postsurgical pain after total knee replacement. The STAR randomised controlled trial (ISCRTN92545361) evaluated the clinical- and cost-effectiveness of a new multifaceted and personalised care pathway, compared with usual care, for people with pain at three months after total knee replacement. We report trial participants’ experiences of postoperative pain and the acceptability of the STAR care pathway, which consisted of an assessment clinic at three months, and up to six follow-up telephone calls over 12 months. Methods Semi-structured interviews were conducted with 27 people (10 men, 17 women) between February 2018 and January 2020. Participants were sampled purposively from the care pathway intervention group and interviewed after completion of the final postoperative trial questionnaire at approximately 15 months after knee replacement. Interviews were audio-recorded, transcribed, anonymised and analysed using inductive thematic analysis. Findings Many participants were unprepared for the severity and impact of postoperative pain, which they described as extreme and constant and that tested their physical and mental endurance. Participants identified ‘low points’ during their recovery, triggered by stiffening, pain or swelling that caused feelings of anxiety, depression, and pain catastrophising. Participants described the STAR assessment clinic as something that seemed “perfectly normal” suggesting it was seamlessly integrated into NHS care. Even in the context of some ongoing pain, the STAR care pathway had provided a source of support and an opportunity to discuss concerns about their ongoing recovery. Conclusions People who have knee replacement may be unprepared for the severity and impact of postoperative pain, and the hard work of recovery afterwards. This highlights the challenges of preparing patients for total knee replacement and suggests that clinical attention is needed if exercise and mobilising is painful beyond the three month postoperative period. The STAR care pathway is acceptable to people with pain after total knee replacement.

Invasive alien species (IAS) are major drivers of global biodiversity loss, and the poorly regulated international pet trade is a source of emerging and future invaders. Predictions of the likely ecological impacts and risks of such IAS have been significantly enhanced in recent years with new metrics, which require application to many more actual and potential IAS. Hence, this study assesses the potential ecological impacts and risks of two readily available pet trade species: goldfish, Carassius auratus, a species with non-native populations worldwide; and white cloud mountain minnow, Tanichthys albonubes, a species with a limited invasion history to date. First, we compared the per capita feeding rates of these non-native species with two European trophically analogous natives – the stone loach, Barbatula barbatula, and the common minnow, Phoxinus phoxinus – using the Comparative Functional Response method. Second, we used foraging experiments in conspecific pairs to determine synergistic, neutral or antagonistic intraspecific interactions. Third, we performed novel object experiments using the two pet trade species to assess boldness, a known “dispersal enhancing trait”. Goldfish had the highest maximum feeding rates of the four species, while white cloud mountain minnows had the lowest. Neutral interactions were observed for all four species in the paired foraging experiments, with goldfish having the highest consumption and white cloud mountain minnows having the lowest. Goldfish demonstrated greater boldness, being more active during the experimental trials and more likely to approach a novel object than white cloud mountain minnows. Further, combining maximum feeding rates, boldness and species availabilities from our survey of pet shops, we assessed the relative invasion risks (RIR) of the two non-natives. This highlighted goldfish as the higher risk and most worthy of management prioritisation, mirroring its more extensive invasion history. We propose that such metrics have potential to direct future IAS policy decisions and management towards the ever-increasing rates of biological invasions worldwide.

Summary: Development of liver fibrosis is paralleled by contraction of hepatic stellate cells (HSCs), the main profibrotic hepatic cells. Yet, little is known about the interplay of neprilysin (NEP) and its substrate neuropeptide Y (NPY), a potent enhancer of contraction, in liver fibrosis. We demonstrate that HSCs are the source of NEP. Importantly, NPY originates majorly from the splanchnic region and is cleaved by NEP in order to terminate contraction. Interestingly, NEP deficiency (Nep−/−) showed less fibrosis but portal hypertension upon liver injury in two different fibrosis models in mice. We demonstrate the incremental benefit of Nep−/− in addition to AT1R blocker (ARB) or ACE inhibitors for fibrosis and portal hypertension. Finally, oral administration of Entresto, a combination of ARB and NEP inhibitor, decreased hepatic fibrosis and portal pressure in mice. These results provide a mechanistic rationale for translation of NEP-AT1R-blockade in human liver fibrosis and portal hypertension.

3D models are increasingly used to study mechanisms driving tumor progression and mimicking in vitro processes such as invasion and migration. However, there is a need to establish more protocols based on 3D culture systems that allow for downstream molecular biology investigations. Materials & methods: Here we present a method for optimal RNA extraction from highly aggressive primary glioma cells invading into Matrigel. The method has been established by comparing previously reported protocols, available commercial kits and optimizing specific steps for matrix dissociation, RNA separation and purification. Results and conclusion: The protocol allows RNA extraction from cells embedded into Matrigel, with optimal yield, purity and integrity suitable for subsequent sequencing analysis of both high and low molecular weight RNA.

ABSTRACT The use of CRISPR-based experiments in an undergraduate course is appealing because of the ease of editing, and the relevance of CRISPR to current research. Before the COVID-19 pandemic, we developed an in-person lab for a high-enrollment course that allowed students to design and conduct CRISPR editing experiments in budding yeast, Saccharomyces cerevisiae. Post pandemic, the lab course moved online, and we lost the hands-on component. We subsequently developed an at-home kit that contained all the necessary materials for students to grow and transform S. cerevisiae with the DNA molecules necessary for CRISPR-Cas9 induced editing. Our at-home kits cost approximately $70 each to produce and were shipped to over 600 students during the 2020 to 2021 academic year. By adding the at-home experimental work to our remote, online lab course, students were able to generate loss-of-function mutants in ADE2 (causing a red color phenotype). Students were able to send edited yeast samples back to campus for sequencing, allowing for characterization of the different mutations that can occur due to CRISPR-Cas9 induced editing. Here, we described the protocol to produce and use the kits and summarized the student experience of using the at-home kit in a large enrollment, remote lab course. These kits provided opportunities to engage students in hands-on experimentation during a remote course and could also be used to reach learners in other domains, such as high schools and outreach programs.

Category: Hindfoot; Ankle Introduction/Purpose: Tranexamic acid (TXA) is an increasingly popular antifibrinolytic therapy used to decrease bleeding during surgery and postoperative swelling. TXA has been shown to decrease bleeding in total knee arthroplasty and total hip arthroplasty, and is now routinely administered in many centers performing these operations. To date, there is very limited data on its use in foot and ankle surgery. We sought to review of the effect of TXA on outcomes of total ankle arthroplasty (TAA), hindfoot fusions, and other related hindfoot surgeries, with the hypothesis that patients receiving TXA would exhibit fewer wound complications. Methods: We conducted a retrospective review of 252 patients (258 operations) undergoing hindfoot fusions and/or TAA between 2015 and 2020 by a single fellowship trained foot and ankle surgeon at an academic medical center. Twenty-seven patients (28 operations) were excluded for less than 90-day follow-up, leaving 230 eligible procedures (TAA=72, subtalar fusion=47, ankle fusion=37, double arthrodesis=33, tibiotalocalcaneal fusion=20, triple arthrodesis=8, total talus=4, and hardware removal=8). Patient demographics, ASA scores, comorbidities, pre-operative diagnoses, smoking status, wound complications, union status (for fusions), readmissions and reoperations were recorded and compared between TXA (n=104) and non-TXA (n=126) cohorts. Subgroup analysis was performed for TAAs and hindfoot fusions. Mean follow-up was 453 days. Continuous variables were compared using independent sample t-test, and categorical variables with chi-square test, unless more than 20% of expected values were less than 5, in which case Fisher's exact tests were utilized. Results: There were no significant differences in demographics, comorbidities, preoperative diagnoses or smoking status between cohorts. The TXA group exhibited significantly less postoperative infections requiring oral antibiotics (5.8% vs. 15.1%, p=.024). These included superficial (p=.174) and deep infections requiring reoperation (p=.095). Subgroup analysis of hindfoot fusions (n=146) revealed significantly shorter time to fusion between TXA and non-TXA groups (146 vs. 202 days, p=.049) and fewer reoperations (8.6% vs. 21.6%, p=.042). TXA fusion patients had significantly shorter follow-up (349 vs. 479 days, p=.020), fewer active smokers (5.2% vs. 15.9%, p=.048), but more patients with Charcot neuroarthropathy (20.7% vs. 5.7%, p=.006). Subgroup analysis of TAAs showed fewer infections requiring oral antibiotics (4.7% vs. 31%, p=.005) and less delayed wound healing (25.6% vs. 48.3%, p=.047) in the TXA cohort. Conclusion: We found TXA use in hindfoot surgery to correlate with a reduction in wound infections requiring antibiotics and quicker time to union in hindfoot fusions. Further, the use of TXA in TAA specifically was correlated with fewer infections requiring antibiotics and lower rates of delayed wound healing. These reductions were both statistically and clinically significant. TXA has already been shown to be beneficial in other areas of orthopaedic surgery and appears to also be quite beneficial in foot and ankle surgery, though further research is needed to confirm these findings.

Brachiosauridae is a lineage of titanosauriform sauropods that includes some of the most iconic non-avian dinosaurs. Undisputed brachiosaurid fossils are known from the Late Jurassic through the Early Cretaceous of North America, Africa, and Europe, but proposed occurrences outside this range have proven controversial. Despite occasional suggestions that brachiosaurids dispersed into Asia, to date no fossils have provided convincing evidence for a pan-Laurasian distribution for the clade, and the failure to discover brachiosaurid fossils in the well-sampled sauropod-bearing horizons of the Early Cretaceous of Asia has been taken to evidence their genuine absence from the continent. Here we report on an isolated sauropod maxilla from the middle Cretaceous (Albian–Cenomanian) Longjing Formation of the Yanji basin of northeast China. Although the specimen preserves limited morphological information, it exhibits axially twisted dentition, a shared derived trait otherwise known only in brachiosaurids. Referral of the specimen to the Brachiosauridae receives support from phylogenetic analysis under both equal and implied weights parsimony, providing the most convincing evidence to date that brachiosaurids dispersed into Asia at some point in their evolutionary history. Inclusion in our phylogenetic analyses of an isolated sauropod dentary from the same site, for which an association with the maxilla is possible but uncertain, does not substantively alter these results. We consider several paleobiogeographic scenarios that could account for the occurrence of a middle Cretaceous Asian brachiosaurid, including dispersal from either North America or Europe during the Early Cretaceous. The identification of a brachiosaurid in the Longshan fauna, and the paleobiogeographic histories that could account for its presence there, are hypotheses that can be tested with continued study and excavation of fossils from the Longjing Formation.

Background: The incidence of pediatric anterior cruciate ligament (ACL) injuries has been increasing over the past 20 years, with the majority comprised of mid substance tears or tibial eminence avulsion fractures. Pediatric femoral sided osseous avulsion is rarely reported in orthopedic literature and specific surgical indications and contraindications, as well as recommended surgical techniques and postoperative rehabilitation protocols, are underdefined. Indications: The surgical indications for femoral-sided repair of ACL osseous avulsion includes a displaced osseous fragment and ligamentous laxity on physical examination. There was no concomitant midsubstance tear necessitating reconstruction. Technique Description: Two sutures piercing the proximal ligamentous bony junction of the ACL were fed through 2.4-mm transphyseal tunnels and secured with cortical button and backup fixation with a 3.9-mm swivel lock anchor in the proximal lateral femoral metaphysis. The patient was immobilized in a hinged-knee brace locked in extension during ambulation and limited to 90 degrees of flexion while nonweightbearing for the first 6 weeks after surgery. Standard ACL protocol was followed thereafter. Results: Successful fixation and restoration of ligamentous tension and impingement-free range of motion were achieved without complication. There was stable Lachman, negative pivot shift, 125 degrees of knee flexion, and evidence of early healing at 3 months follow-up. Discussion/Conclusion: This report demonstrates successful reduction and fixation of proximal bony avulsion of the ACL. Although this patient exhibits stable physical examination and undisturbed growth at early follow-up, more research is required to establish treatment and rehabilitation guidelines for this rare injury.

This paper analyzes the development and implementation of a game-based learning course design framework. Drawing inspiration from task-based learning, the framework is structured around four core gamified elements: narrative assignment design; learner discovery; team-based collaboration and competition; and choice through quests. The intended goal of implementing this framework is to improve learner engagement and foster greater learner investment in the course. The framework, developed at the University of Waterloo, was integrated into the course design for—and subsequently taught in—a third-year history course. A mixed-methods analysis was conducted in which students (n = 15) were surveyed, interviewed, and observed throughout the course at different intervals. The results of the study suggest that the team-based nature of the framework and the embedded gameplay elements are most effective at improving engagement for learners, while some form of extrinsic motivation is still beneficial to ensure all learners find completing additional tasks worthwhile.

Numerous studies have demonstrated that gene transfer events (e.g., plasmid acquisition) can entail a variety of costs that arise as by-products of the incorporation of foreign DNA into established physiological and genetic systems. These costs can be ameliorated through evolutionary time by the occurrence of compensatory mutations, which stabilize the presence of a horizontally transferred region within the genome but which also may skew future adaptive possibilities for these lineages.

A retrospective study revealed ten cases of emphysematous ingluvitis in Loriinae birds from two zoological collections between 2009 and 2020. Common clinical features were sudden death with gas distention of the crop, subcutaneous cervical emphysema and poor body condition, but also included collapse, hypothermia and abandonment. Macroscopic examination revealed moderate crop enlargement, distention and thickening with minimal intraluminal content, and moderate to severe submucosal to transmural gas-filled cysts (emphysema). Histopathology identified widespread transmural multifocal to coalescing empty pseudo-cystic cavities with lytic necrosis, pyo-/granulomatous inflammatory infiltrates, epithelial ulceration, parakeratotic hyperkeratosis, epithelial ballooning degeneration, and occasional intralesional rod-shaped bacteria. The lesion may have impaired the birds' ability to ingest food, resulting in suboptimal body condition. Necrotizing to granulomatous aspiration pneumonia was also a feature in some cases. Anaerobic bacterial culture of four crops identified Clostridium perfringens with associated toxin genes for alpha and occasionally beta2 toxin (cpa and cpb2 genes respectively), by PCR analysis of bacterial isolates cultured from fresh or frozen tissue. C. perfringens was identified as the common etiological agent of emphysematous ingluvitis in crop and/or liver (six out of ten birds), and type A was confirmed in five birds. C. perfringens was not detected in the crop nor liver of two unaffected Loriinae birds. This is the first publication that characterizes nectarivorous bird emphysematous ingluvitis (NBEI), attributes C. perfringens as an etiological agent, and highlights this novel disease as an important cause of death in Loriinae birds, particularly in nestling and fledgling stage of development, but also in older lorikeets and lories.

Zeta-chain-associated protein kinase-70 (ZAP-70) is a tyrosine kinase mainly expressed in T cells, NK cells and a subset of B cells. Primarily it functions in T cell receptor (TCR) activation through its tyrosine kinase activity. Aberrant expression of ZAP-70 has been evidenced in different B cell malignancies, with high expression of ZAP-70 in a subset of patients with Chronic Lymphocytic Leukemia (CLL), associating with unfavorable disease outcomes. Previous studies to understand the mechanisms underlying this correlation have been focused on tumor intrinsic mechanisms, including the activation of B cell receptor (BCR) signaling. Recent evidence also suggests that ZAP-70, intrinsically expressed in tumor cells, can modulate the cross-talk between malignant B cells and the immune environment, implying a more complex role of ZAP-70 in the pathogenesis of B cell malignancies. Meanwhile, the indispensible roles of ZAP-70 in T cell and NK cell activation also demonstrate that the autologous expression of ZAP-70 in the immune environment can be a central target in modulation of tumor immunity. Here we review the evidences of the link between ZAP-70 and tumor immunology in the microenvironment in B cell malignancies. Considering an emerging role of immunotherapies in treating these conditions, understanding the distinct molecular functions of ZAP-70 in a broader cellular context could ultimately benefit patient care.

Introduction: The mortality of patients with neck-of-femur (NOF) fractures remains high, with increasing recognition of a subgroup of patients with predictable mortality. The role of palliative care in this group is poorly understood and underdeveloped. This research aims to investigate current clinician attitudes toward palliative care for patients with NOF fracture, and explore processes in place for early identification for patients nearing the end of life. Materials and Methods: An online survey was constructed with reference to National Institute for Health and Clinical Excellence end-of-life guidelines (CG13) and distributed to multidisciplinary teams involved in the care of NOF fracture patients in 4 hospitals of contrasting size and location in the United Kingdom. Results: Forty health-care professionals with a broad range of seniority and roles responded. The palliative care team was felt to have several potential roles in the care of NOF fracture patients, but there was difference of opinion between specialties about what these were. A number of barriers to palliative referral were identified, including stigma and active surgical management. The majority (75%) felt that all NOF fracture patients should have a discussion about ceiling of care, with difference of opinion about who should do so, and when. Discussion: As the elderly population has grown, so too has the volume of NOF fracture patients. It is increasingly important to identify and escalate patients who have poor prognosis following hip fracture and ensure they benefit from palliative care where appropriate. This survey demonstrates a barrier to addressing the care of these patients and a lack of consensus on identification and referral to appropriate palliative care planning. Conclusions: There should be close communication between specialties with regard to requirements for palliative care in NOF fracture patients, with ongoing education and clear local and national guidance to ensure they receive the right care at the right time.

BackgroundThis is a multi-method, in-depth, three part qualitative study exploring the regulation and practice of secondary research with tissue and data in a high-income country. We explore and compare the perspectives of researchers, research ethics committees (RECs) and other relevant professionals (e.g. pathologists and clinicians). We focus on points of contention because they demonstrate misalignment between the expectations, values and assumptions of these stakeholders.MethodsThis is a multi-method study using observational research, focus groups and interviews with 42 participants (conducted 2016-2017) and analyzed using thematic analysis.ResultsResults are arranged under the following themes: consent; balancing the social value of the research with consent requirements; and harm. Our findings demonstrate different perspectives on the review process, styles of ethical reasoning and issues of concern. First, researchers and RECs disagreed about whether the cost of re-consenting patients satisfied the criterion of impracticability for consent waivers. Second, most researchers were skeptical that secondary research with already collected tissue and data could harm patients. Researchers often pointed to the harm arising from a failure to use existing material for research. RECs were concerned about the potential for secondary research to stigmatize communities. Third, researchers adopted a more consequentialist approach to decision-making, including some willingness to trade off the benefit of the research against the cost of getting consent; whereas RECs were more deontological and typically considered research benefit only after it had been established that re-consent was impractical.ConclusionThis research highlights ways in which RECs and researchers may be talking past each other, resulting in confusion and frustration. These finding provide a platform for realignment of the expectations of RECs and researchers, which could contribute to making research ethics review more effective.

The Wnt pathway is one of the core de-regulated pathways in chronic lymphocytic leukaemia (CLL) and is activated in only a subset of patients; however, no universal drivers of the disease have been identified. Here the authors show that Notch2 and β-catenin pathways are the main drivers of the pro-survival bidirectional crosstalk between stromal cells and leukemic cells.

Collaboration between the Rwandan government, the University of Rwanda, and local industry to develop and deploy educator technology-integration professional development initiatives neatly follows the Triple Helix Model[1]. However, in this Rwandan initiative a fourth collaborative partner proved significant, the regional/global education community coordinated by UNESCO's Regional Office for Eastern Africa. The ICT Essentials for Teachers' Course was designed to exploit a blended-learning methodology, developed using Open Educational Resources and deployed by locally trained online facilitators. This paper presents a model of how effective collaboration between stakeholders can result in the quick and cost-effective development and deployment of educator training initiatives that are scalable.

Background: Objective-structured teaching encounters (OSTEs) are used across many disciplines to assess teaching ability. The OSTE detailed in this paper assesses 191 fourth-year medical students’ (M4) ability to identify and address lapses in professionalism based on Association of American Medical Colleges’ professionalism competencies. The research questions addressed are• How frequently do M4s address professionalism lapses observed during an OSTE?• What factors influence whether M4s provide feedback when they observe professionalism lapses in an OSTE? Methods: Standardized patients (SPs) and standardized learners (SLs) were recruited and trained to participate in a standardized encounter with specific cognitive, social, and behavioral errors, including professionalism lapses. M4s viewed this encounter and then offered feedback to the SL, while remotely observed by faculty. Post-encounter, the SL and faculty completed identical checklists to assess both teaching readiness and ability to address professionalism concerns. Results: An analysis of frequencies showed that six of the Association of American Medical Colleges’ nine professional competencies were addressed in the checklist and/or discussed in the focus group. Analysis of transcribed debriefing sessions confirmed that M4s did not consistently address professionalism lapses by their peers. Conclusions: In focus groups, M4s indicated that, while they noticed professionalism issues, they were uncomfortable discussing them with the SLs. Findings of the current study suggest how medical educators might support learners’ ability to address lapses in professionalism as well as topics for future research.

Operational oceanography can be described as the provision of routine oceanographic information needed for decision-making purposes. It is dependent upon sustained research and development through the end-to-end framework of an operational service, from observation collection to delivery mechanisms. The core components of operational oceanographic systems are a multi-platform observation network, a data management system, a data assimilative prediction system, and a dissemination/accessibility system. These are interdependent, necessitating communication and exchange between them, and together provide the mechanism through which a clear picture of ocean conditions, in the past, present, and future, can be seen. Ocean observations play a critical role in all aspects of operational oceanography, not only for assimilation but as part of the research cycle, and for verification and validation of products. Data assimilative prediction systems are advancing at a fast pace, in tandem with improved science and the growth in computing power. To make best use of the system capability these advances would be matched by equivalent advances in operational observation coverage. This synergy between the prediction and observation systems underpins the quality of products available to stakeholders, and justifies the need for sustained ocean observations. In this white paper, the components of an operational oceanographic system are described, highlighting the critical role of ocean observations, and how the operational systems will evolve over the next decade to improve the characterization of ocean conditions, including at finer spatial and temporal scales.

Abstract. Introduction:. With the increasing availability of cannabis and cannabinoids and their potential utility for pain treatment, there is a growing need to evaluate the risk-benefit considerations of cannabinoids for the management of pain. As part of the IASP Cannabis and Cannabinoids Task Force, this protocol describes a planned overview of systematic reviews summarizing the risks of harm with cannabinoids that are relevant to patients receiving pain treatment. Methods:. This overview will involve literature searches of several databases and a defined search strategy that will target systematic reviews or meta-analyses of cannabinoids where harms are the primary focus. Data extraction will include various features of the cannabinoid(s) and the harm(s) being studied as well as other methodological features of each included systematic review. Methodological quality of each included review will be assessed using AMSTAR-2 as well as compliance with the PRISMA harms checklist. Prospero registration pending. Discussion:. The broad overview of reviews defined by this protocol is expected to synthesize available good quality evidence of harms that will help inform risk-benefit considerations about the use of cannabinoids for pain management.

Hollow fibre membrane contactor (HFMC) technology has been developed for CO2 absorption primarily using synthetic gas, which neglects the critical impact that trace contaminants might have on separation efficiency and robustness in industrial gases. This study, therefore, commissioned a demonstration-scale HFMC for CO2 separation at a full-scale anaerobic digester facility to evaluate membrane integrity over six months of operation on real biogas. The CO2 capture efficiency identified using real biogas was benchmarked at comparable conditions on synthetic gas of an equivalent partial pressure, and an equivalent performance identified. Two HFMC were subsequently compared, one with and one without a pre-treatment stage that targeted particulates, volatile organic compounds (VOCs) and humidity. Similar CO2 separation efficiency was again demonstrated, indicating limited impact within the timescale evaluated. However, gas phase pre-treatment is advised in order to ensure robustness in the long term. Over longer-term operation, a decline in CO2 separation efficiency was observed. Membrane autopsy identified shell-side deposition, where the structural morphology and confirmation of amide I and II groups, indicated biofouling. Separation efficiency was reinstated via chemical cleaning, which demonstrated that proactive maintenance could minimise process risk.

In the United States, Lyme disease is caused by Borrelia burgdorferi and transmitted to humans by blacklegged ticks. Patients with an erythema migrans lesion and epidemiologic risk can receive a diagnosis without laboratory testing. For all other patients, laboratory testing is necessary to confirm the diagnosis, but proper interpretation depends on symptoms and timing of illness. The recommended laboratory test in the United States is 2-tiered serologic analysis consisting of an enzyme-linked immunoassay or immunofluorescence assay, followed by reflexive immunoblotting. Sensitivity of 2-tiered testing is low (30%–40%) during early infection while the antibody response is developing (window period). For disseminated Lyme disease, sensitivity is 70%–100%. Specificity is high (>95%) during all stages of disease. Use of other diagnostic tests for Lyme disease is limited. We review the rationale behind current US testing guidelines, appropriate use and interpretation of tests, and recent developments in Lyme disease diagnostics.

Bioelectrochemical systems (BES) have the potential to deliver energy-neutral wastewater treatment. Pilot-scale tests have proven that they can operate at low temperatures with real wastewaters. However, volumetric treatment rates (VTRs) have been low, reducing the ability for this technology to compete with activated sludge (AS). This paper describes a pilot-scale microbial electrolysis cell (MEC) operated in continuous flow for 6 months. The reactor was fed return sludge liquor, the concentrated filtrate of anaerobic digestion sludge that has a high chemical oxygen demand (COD). The use of a wastewater with increased soluble organics, along with optimisation of the hydraulic retention time (HRT), resulted in the highest VTR achieved by a pilot-scale MEC treating real wastewater. Peak HRT was 0.5-days, resulting in an average VTR of 3.82 kgCOD/m3∙day and a 55% COD removal efficiency. Finally, using the data obtained, a direct analysis of the potential savings from the reduced loading on AS was then made. Theoretical calculation of the required tank size, with the estimated costs and savings, indicates that the use of an MEC as a return sludge liquor pre-treatment technique could result in an industrially viable system.

The removal of phosphorus (P) from domestic wastewater is primarily to reduce the potential for eutrophication in receiving waters, and is mandated and common in many countries. However, most P-removal technologies have been developed for use at larger wastewater treatment plants that have economies-of-scale, rigorous monitoring, and in-house operating expertise. Smaller treatment plants often do not have these luxuries, which is problematic because there is concern that P releases from small treatment systems may have greater environmental impact than previously believed. Here P-removal technologies are reviewed with the goal of determining which treatment options are amenable to small-scale applications. Significant progress has been made in developing some technologies for small-scale application, namely sorptive media. However, as this review shows, there is a shortage of treatment technologies for P-removal at smaller scales, particularly sustainable and reliable options that demand minimal operating and maintenance expertise or are suited to northern latitudes. In view of emerging regulatory pressure, investment should be made in developing new or adapting existing P-removal technologies, specifically for implementation at small-scale treatment works.

Knee replacement is a common preference sensitive quality-of-life procedure that can reduce pain and improve function for people with advanced knee arthritis. While most patients improve, knee replacement surgery has the potential for serious complications. Prosthetic knee infection is an uncommon but serious complication. This study explored the impact of cases of prosthetic knee infection on surgeons' personal and professional wellbeing. Qualitative telephone interviews were conducted with consultant orthopaedic surgeons who treated patients for prosthetic knee infection in one of six high-volume NHS orthopaedic departments. Data was audio-recorded, transcribed and analysed thematically. Eleven surgeons took part. Analysis identified three overarching themes: (i) At some point infection is inevitable but surgeons still feel accountable; (ii) A profound emotional impact and (iii) Supporting each other. The occurrence of prosthetic joint infection has a significant emotional impact on surgeons who report a collective sense of devastation and personal ownership, even though prosthetic joint infection cannot be fully controlled for. Surgeons stressed the importance of openly discussing the management of prosthetic joint infection with a supportive multidisciplinary team and this has implications for the ways in which orthopaedic surgeons may be best supported to manage this complication. This article also acknowledges that surgeons are not alone in experiencing personal impact when patients have infection.

Calibration weighting improves inference by adjusting for observed differences between the realized sample and the population. Unfortunately, a commonly-used linearization-based variance estimator often does not account for the increased efficiency provided by the calibration process. As a result, precision estimates based on calibrated weights can be artificially high. Using a relatively new alternative linearization-based variance estimator allows analysts to utilize calibration-weighting techniques while producing more accurate precision estimates. We use calibration weighting to produce more reliable subnational estimates and assess the differences in point estimates resulting from these weight adjustments in the National Crime Victimization Survey, a nationally representative survey designed to calculate victimization rates solely at the national level. We then assess the estimated precision of these point estimates using a conventional linearization-based variance estimator and the alternative estimator. We find that the calibration adjustments mostly reduced the standard errors in subnational estimates but to successfully measure the reduction required using the alternative variance estimator.

The deployment of small unmanned aircraft systems (UAS) to collect routine in situ vertical profiles of the thermodynamic and kinematic state of the atmosphere in conjunction with other weather observations could significantly improve weather forecasting skill and resolution. High-resolution vertical measurements of pressure, temperature, humidity, wind speed and wind direction are critical to the understanding of atmospheric boundary layer processes integral to air−surface (land, ocean and sea ice) exchanges of energy, momentum, and moisture; how these are affected by climate variability; and how they impact weather forecasts and air quality simulations. We explore the potential value of collecting coordinated atmospheric profiles at fixed surface observing sites at designated times using instrumented UAS. We refer to such a network of autonomous weather UAS designed for atmospheric profiling and capable of operating in most weather conditions as a 3D Mesonet. We outline some of the fundamental and high-impact science questions and sampling needs driving the development of the 3D Mesonet and offer an overview of the general concept of operations. Preliminary measurements from profiling UAS are presented and we discuss how measurements from an operational network could be realized to better characterize the atmospheric boundary layer, improve weather forecasts, and help to identify threats of severe weather.

HIV and Helicobacter pylori are common chronic infections in sub-Saharan Africa. Both conditions can predispose to gastric hypochlorhydria that may be a risk factor for enteric infections and reduced drug absorption. We have investigated to what extent HIV and H. pylori infections are associated with hypochlorhydria in a Malawian cohort of patients undergoing endoscopy.104 sequential symptomatic adults referred for gastroscopy at Queen Elizabeth Central Hospital, Blantyre, Malawi, had blood taken for rapid HIV testing and fasting serum gastrin analysis. Gastric fluid was aspirated for pH testing, and gastric biopsies were taken.After 9/104 HIV-infected patients who were already established on anti-retroviral therapy were excluded, 17/95 (25.0%) were seropositive for untreated HIV, and 68/95 (71.6%) patients were H. pylori positive by histology. Hypochlorhydria (fasting gastric pH>4.0) was present in 55.8% (53/95) of patients. H. pylori infection was significantly associated with hypochlorhydria (OR 2.91, [1.02-7.75], p=0.046). While single infection with HIV was not significantly independently associated with hypochlorhydria. H. pylori and HIV co-infection was more strongly associated with hypochlorhydria (OR 6.25, [1.33-29.43], p=0.020) than either infection alone, suggesting an additive effect of co-infection. HIV infection was associated with higher serum gastrin levels (91.3 pM vs. 53.1 pM, p=0.040), while H. pylori infection was not (63.1 pM vs. 55.1 pM, p=0.610). Irrespective of H. pylori and HIV status, most patients (>90%) exhibited pangastritis. Only three patients had histological evidence of gastric atrophy, of which only one was HIV-infected.H. pylori infection was associated with fasting hypochlorhydria, while HIV was not independently associated. HIV and H. pylori co-infection, however, was more strongly associated with hypochlorhydria than H. pylori infection alone. The mechanism of this apparent additive effect between HIV and H. pylori remains unclear, but appears to be related to chronic pangastritis rather than gastric atrophy, and associated with hypergastrinaemia in HIV-infected individuals.

This paper reports on two action research projects which explored the challenge of determining the conditions under which use of OER can drive a transformative educational agenda in schooling systems. At St Peter’s College in Johannesburg, South Africa, a small pilot study was conducted to explore how to best to adopt new teaching and learning methodologies to encourage greater student engagement and responsibility, and to gauge student and staff reactions to a change in teaching and learning methodologies. It placed heavy emphasis on harnessing OER to enable student-led content creation, with a long-term view of demonstrating that students can use OER to create self-paced learning environments that significantly accelerate their journey through the formal curriculum. In Antigua and Barbuda, the research project considered how to facilitate an entire system to change. It recognised that for change to be effective, it needs to be driven at the systemic level, as these ultimately direct the operations of most public schooling systems. The paper explores the different steps taken, starting from the government’s commitment to ICT infrastructure, fostering a policy environment through an ICT in Education policy and an ICT Master Plan to guide procurement and deployment of ICT in schools, and the development of a School ICT integration plan to ensure school’s ICT needs and requirements. The research explored the deployment of an OER Virtual learning Environment (VLE) Prototype, and the compilation of an online mathematics ‘textbook’ from available quality free OER. The paper concludes by highlighting the kinds of systemic actions required for the proponents of OER to build sustained pressure for long-term, educationally effective systemic change.

The Ministry of Education in Guyana has prioritised increasing the number of qualified teachers by providing opportunities to both pre- and in-service teachers to gain relevant qualifications. This paper describes the process used to redesign the teacher training curriculum in Guyana to achieve the goals of a newly-developed ICT Professional Development Strategy. The UNESCO ICT Competency Framework for Teachers (CFT) was central to the redesign process, and was used to review and reorganize the national teacher education curriculum aimed at pre-service teachers. The framework also influenced plans to provide professional development for in-service teachers, and influenced the selection of Open Education Resources (OER) used to develop a new learning environment and the accompanying learning materials for the teaching of ICT in Education. One of the significant lessons learned during this process is that people rather than technology are crucial to transformation. It is essential to have leadership support at the highest levels but also committed champions at all other levels. The process called for the inclusion of local stakeholders who understood and knew how to respond to contextual constraints. Moreover, the process benefited from the use of existing frameworks and the use of cost effective OER to develop the course materials.

Abstract Background Ageing populations will impact on healthcare provision, especially since extra years are not necessarily spent in good health. It is important to identify and understand the significance of common medical problems in older people. Anaemia may be one such problem. We report on the prevalence of anaemia in cohorts of elderly people in the general population. The presence of anaemia is associated with a worse prognosis for both morbidity and mortality. Methods Electronic searching and reference lists of published reports were used to identify studies that reported on prevalence of anaemia in cohorts of at least 100 individuals predominantly aged 65 years and over living in developed countries, together with criteria used to define anaemia. Studies of anaemia prevalence in specific disease groups or published before 1980 were excluded. Prevalence data for the entire cohort, for men and women separately and for different age bands were extracted. Results Forty-five studies contributed data. Thirty-four studies (n = 85,409) used WHO criteria to define anaemia. The weighted mean prevalence was 17% (3–50%) overall, and 12% (3–25%) in studies based in the community (27, n = 69,975), 47% (31–50%) in nursing homes (3, n = 1481), and 40% (40–72%) in hospital admissions (4, n = 13,953). Anaemia prevalence increased with age, was slightly higher in men than women, and was higher in black people than white. Most individuals classified as anaemic using WHO criteria were only mildly anaemic. Conclusion Anaemia, as defined by WHO criteria, is common in older people living in the community and particularly common in nursing home residents and hospital admissions. Predicted demographic changes underline the need to understand more about anaemia in older people.