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Background Matrix metalloproteinase 9 (MMP9) expression in the tumor microenvironment is implicated in multiple protumorigenic processes. Andecaliximab (GS-5745), a monoclonal antibody targeting MMP9 with high affinity and selectivity, was evaluated in combination with gemcitabine and nab-paclitaxel in patients with advanced pancreatic adenocarcinoma. Patients and Methods This phase I study was completed in two parts: part A was a dose-finding, monotherapy phase that enrolled patients with advanced solid tumors, and part B examined andecaliximab in combination with chemotherapy in specific patient cohorts. In the cohort of patients with pancreatic adenocarcinoma (n = 36), andecaliximab 800 mg every 2 weeks was administered in combination with gemcitabine and nab-paclitaxel. Patients were treated until unacceptable toxicity, withdrawal of consent, disease progression, or death. Efficacy, safety, and biomarker assessments were performed. Results Andecaliximab combined with gemcitabine and nab-paclitaxel appeared to be well tolerated and did not demonstrate any unusual toxicities in patients with pancreatic adenocarcinoma. The most common treatment-emergent adverse events were fatigue (75.0%), alopecia (55.6%), peripheral edema (55.6%), and nausea (50.0%). Median progression-free survival was 7.8 months (90% confidence interval, 6.9−11.0) with an objective response rate of 44.4% and median duration of response of 7.6 months. Maximal andecaliximab target binding, defined as undetectable, andecaliximab-free MMP9 in plasma, was observed. Conclusion Andecaliximab in combination with gemcitabine and nab-paclitaxel demonstrates a favorable safety profile and clinical activity in patients with advanced pancreatic adenocarcinoma. Implications for Practice The combination of andecaliximab, a novel, first-in-class inhibitor of matrix metalloproteinase 9, with gemcitabine and nab-paclitaxel in patients with advanced pancreatic adenocarcinoma provided a median progression-free survival of 7.8 months and objective response rate of 44.4%. The majority of systemic biomarkers related to matrix metalloproteinase 9 activity and immune suppression increased at 2 months, whereas biomarkers related to tumor burden decreased. Although this study demonstrates promising results with andecaliximab plus chemotherapy in patients with advanced pancreatic adenocarcinoma, andecaliximab was not associated with a survival benefit in a phase III study in patients with advanced gastric/gastroesophageal junction carcinoma.

Introduction Triathlon is one of the fastest growing sports in the United Kingdom. However, in recent years several deaths have occurred. The intention of this study is to identify these cases and examine the role cardiovascular disease played in these deaths. Methods An extensive online search was performed to identify triathlon-related deaths (TRDs) in the United Kingdom and UK citizens who died during or as a result of competing in triathlons abroad. British Triathlon provided the number of participants who took part in UK-based events. Coroners provided information on all those who died. Results Between 2009 and 2015, 991,186 participants took part in British Triathlon-sanctioned events. Five TRDs in the United Kingdom were identified. The mortality rate was 0.5 per 100,000 participants. Deaths occurred during or after the swim (3), cycle (1), and run (1) events. During the same period, 5 TRDs were identified among UK citizens competing abroad. These deaths occurred during or after the swim (2), cycle (1), and run (2) events. Cardiovascular pathology was cited as a cause or contributing factor in half of the fatalities. Four deaths were referred to a specialist cardiac pathology service for autopsy. Conclusions Cardiovascular disease was found to be the most common cause of TRD. Further research is needed to determine the underlying cardiac pathology that triggers TRDs. With this information it may be possible to develop screening tools that can prevent similar fatalities from occurring in the future.

The Bridging the Word Gap Research Network conducted a review of literature to identify effective interventions to facilitate the communication development of young children in hopes of identifying ways to reduce the well-documented word gap among children associated with socio-economic class. As part of this effort, we focused on the ways in which caregivers (teachers, parents, and others) were taught to implement evidence-based practices for facilitating language learning and use. Our goal was to characterize (a) the implementation fidelity, to describe the teaching functions and implementation procedures for teaching those language intervention strategies and (b) the intervention fidelity with which caregivers used strategies for facilitating their children’s language development. Because training procedures are not well described in the implementation and professional development literature, a new framework was developed and its feasibility was assessed in an attempt to characterize the teaching functions and specific implementation procedures used across studies. Among the 270 intervention studies reviewed, there were 124 in which caregivers were taught to implement language intervention strategies. Teaching functions included a variety of implementation procedures, with 95% of studies sharing information, 80% incorporating modeling, 65% providing feedback, and only 18% using prompting/guiding/scaffolding. Seventy-two of these studies (58%) reported intervention fidelity, with an increasing proportion reporting fidelity in recent years. Of these 72 studies, 81% were rated as having a ‘moderate to strong’ description of fidelity measures, and 50% reported high levels of intervention fidelity (i.e., >70% fidelity). These analyses demonstrate the need for reporting more detailed and precise information on intervention fidelity and the teaching functions and procedures used to teach caregivers to implement language interventions.

This study uses a single-case, multiple probe design to investigate the effects of a naturalistic intervention on deictic gesture use in toddlers who are from low-SES backgrounds. The month-long study included strategies drawn from the literature on early communication interventions to increase the rate of child gesture use in toddlers at-risk for later delays. These strategies include frequent modeling of deictic gestures (points, shows, reaches, and gives), creating opportunities for the child to gesture by using environmental arrangements, choices, and wait time, and by responding and expanding each gesture. All three child participants made gains in their rates of deictic gestures after the onset of intervention with no overlap between the intervention and baseline conditions. Children also made gains to gesture + vocalization combinations and gesture + word combinations in this short-term intervention. This study offers preliminary evidence that prelinguistic interventions for children at-risk can be used to increase rates of communication in toddlers in poverty.

The purpose of this study was to examine the effects of coaching caregivers to embed both communication and motor outcomes concurrently within daily routines of their infants or toddlers with significant disabilities using Enhanced Milieu Teaching (EMT) strategies. The coaching and embedding practices were part of a multicomponent intervention known as Embedded Practices and Intervention with Caregivers (EPIC). Three children, aged 15 to 23 months with significant disabilities, their caregivers, and an early intervention provider participated in this single case multiple probe design study. Primary dependent variables were caregivers’ number of naturalistic teaching strategies used and rates of correctly embedded instruction for each learning target in each routine. Child motor and communication outcomes were also examined. Results provide initial support for the positive effects of the EPIC approach using EMT strategies to embed intervention on two developmental domains concurrently in caregiver’s daily routines.

Academic research that examines different leadership models utilised in the digital age within ICT4D that facilitates the Fourth Industrial Revolution for the marginalised people are scarce. This study focused on the e-Sri Lanka program, initially funded by the World Bank as a unique South Asian project that established a network of 1,005 Nenasala telecentres. Sri Lanka is further focused on building an e-smart, e-inclusive society through ICT4D. In 2020, the Nenasala 2.0 initiative is to be expanded on the Nenasala network to scale up e-society innovations. This context provides an exciting research bedrock to explore. The research findings revealed that leadership at various organisational levels will be key to Nenasala 2.0 and ICT4D program sustainability. The Nenasala model that benefitted from unique community-based leadership was termed socio-cultural leadership. A replication of the study in other developing countries to identify the leadership needed in ICT4D could prove invaluable as it may identify viable complementary options to commercially orientated telecentres.

Despite an emphasis in the field on triadic approaches to the delivery of early intervention (EI), remarkably little is known about the shared experiences of caregivers (CGs) and providers during home visits. Within the context of developing, refining, and evaluating the Embedded Practices and Intervention With Caregivers (EPIC) approach, two studies were undertaken with 11 EI providers and 19 CGs of infants/toddlers with moderate–severe delays/disabilities to gather their perspectives about and experiences with the EPIC approach. The EPIC intervention has two components: CG coaching and a five-question (5Q) process for supporting embedded practices. Interview, focus group, and rating scale data were collected in both studies and aggregated for reporting purposes in the present article. Findings are described with regard to the coaching and 5Q components and the extent to which participants found the intervention to be feasible, acceptable, and useful. Implications for future research and professional development on coaching and embedded intervention practices are discussed.

Purpose: Matrix metalloproteinase-9 (MMP9) is implicated in protumorigenic processes. Andecaliximab (GS-5745, a monoclonal antibody targeting MMP9) was evaluated as monotherapy and in combination with mFOLFOX6. Patients and Methods: Three dosages of andecaliximab monotherapy [200, 600, and 1800 mg i.v. every 2 weeks (q2w)] were investigated in patients with advanced solid tumors (n = 13 in a 3+3 design). After determining a recommended dose, patients with advanced HER2-negative gastric/gastroesophageal junction (GEJ) adenocarcinoma (n = 40) received 800 mg andecaliximab + mFOLFOX6 q2w. Pharmacokinetics, pharmacodynamics, safety, and efficacy were assessed. Results: Andecaliximab monotherapy demonstrated no dose-limiting toxicity (DLT) in any cohort, displaying target-mediated drug disposition at the lowest dose (200 mg) and linear pharmacokinetics at higher doses. Based on target engagement, recommended doses for further study are 800 mg q2w or 1,200 mg q3w. Maximal andecaliximab target binding, defined as undetectable andecaliximab-free MMP9 in plasma, was observed in the gastric/GEJ adenocarcinoma cohort. We observed no unusual toxicity, although there were four deaths on study not attributed to andecaliximab treatment. In first-line patients (n = 36), median progression-free survival (PFS) was 9.9 months [95% confidence interval (CI), 5–13.9 months], and the overall response rate (ORR) was 50%. Among all patients (n = 40), median PFS was 7.8 (90% CI, 5.5–13.9) months, and ORR was 48%, with a median duration of response of 8.4 months. Conclusions: Andecaliximab monotherapy achieved target engagement without DLT. Andecaliximab + mFOLFOX6 showed encouraging clinical activity without additional toxicity in patients with HER2-negative gastric/GEJ adenocarcinoma. A phase III study evaluating mFOLFOX6 ± andecaliximab in this setting is ongoing. Clin Cancer Res; 24(16); 3829–37. ©2018 AACR.

A method has been developed to fabricate patterned arrays of micrometer-sized monodisperse solid particles of ammonium nitrate on hydrophobic silicon surfaces using inkjet printing. The method relies on dispensing one or more microdrops of a concentrated aqueous ammonium nitrate solution from a drop-on-demand (DOD) inkjet printer at specific locations on a silicon substrate rendered hydrophobic by a perfluorodecytrichlorosilane monolayer coating. The deposited liquid droplets form into the shape of a spherical shaped cap, during the evaporation process, a deposited liquid droplet maintains this geometry until it forms a solid micrometer sized particle. Arrays of solid particles are obtained by sequential translation of the printer stage. The use of DOD inkjet printing for fabrication of discrete particle arrays allows for precise control of particle characteristics (mass, diameter and height), as well as the particle number and spatial distribution on the substrate. The final mass of an individual particle is precisely determined by using gravimetric measurement of the average mass of solution ejected per microdrop. The primary application of this method is fabrication of test materials for the evaluation of spatially-resolved optical and mass spectrometry based sensors used for detecting particle residues of contraband materials, such as explosives or narcotics.

The chemical profiles of Tasmanian Leatherwood and Manuka honeys from Tasmania and New Zealand have been compared by a combination of GC-MS analysis of volatiles and semi-volatiles, RP-HPLC-DAD analysis of phenolics and flavonoids and HPLC-DAD analysis of derivatised dihydroxyacetone, hydroxymethylfurfural and methylglyoxal. This study found that Tasmanian and New Zealand Manuka honeys have high concentrations of methylglyoxal. However, syringic acid was only detected in Manuka honeys grown in New Zealand. The Tasmanian honeys can be distinguished by the higher concentration of 3-phenyllactic acid in Manuka compared to Leatherwood floral sources.

Crowdfunding could be the path to assist Nenasalas in the future, considering traditional financial institutions have largely ignored this grass-roots initiative.

The number of persons visiting high altitude regions for various purposes (recreation, business etc.), and the age of people who do so, increases. Therefore there are more and more patients who need specific and individual advice to prevent emergency situations at altitude and to deal with emergencies if the safety strategy should fail. Since literature concerning cardiocirculatory diseases at altitude is scarce and studies with a controlled setting and high evidence level are missing, UIAA MedCom has checked all available literature for specific information to enable physicians who are active in travel or high altitude medicine to advise the patients at the highest possible level of evidence. It must be pointed out that there are several other medical fields where such information is mandatory, e.g. in occupational medicine, when employees depart to high altitude destinations for business purposes. The recommendations are based on a detailed literature research (databases, handbooks and the respective references). For easier use the paper has been structured as follows: general information, cardiocirculatory system and ECG at altitude, several cardiocirculatory diseases and their specific recommendations. The commission concludes, that a general "don't go!" is no state-of-the-art advice for the patients. With the information presented here a safe trip to altitude should be possible for many patients.

This phase III, multicenter, single-arm trial investigated the impact of 90 min rituximab infusions on infusion-related reactions (IRRs) in patients with untreated diffuse large B-cell lymphoma (DLBCL) or follicular lymphoma (FL). Patients received six or eight cycles of rituximab plus cyclophosphamide, vincristine, doxorubicin and prednisone for DLBCL or plus cyclophosphamide, vincristine and prednisolone for FL. A total of 425 patients received the first rituximab infusion per standard guidelines; median duration 240 min. Patients who did not experience grade ≥ 3 IRRs received subsequent infusions over 90 min (363 patients). A total of 303 patients received ≥ 6 cycles of rituximab. Fifty-three patients withdrew after cycle 1; 10 for grade 3 or 4 IRRs and one for a grade 3 adverse event. During cycle 2, 139 patients had IRRs, including four grade 3 IRRs. A 90 min rituximab infusion is well tolerated and feasible for patients with DLBCL or FL who tolerate the first standard rate infusion.

The Wilderness Medical Society convened an expert panel to develop evidence-based guidelines for the management of pain in austere environments. Recommendations are graded based on the quality of supporting evidence as defined by criteria put forth by the American College of Chest Physicians.

Purpose of review The aim is to describe the impact of altitude upon sleep, the physiology that underpins these changes and the therapeutic solutions that are currently in place. Recent findings On ascending to altitude, lowland residents commonly experience some degree of sleep disturbance. Occasionally, this can prove very uncomfortable and impact upon daytime activities. Historically, the underlying cause of sleep disturbance was thought to be due to the effect of periodic breathing. However, recent research has shown that the link between periodic breathing, lighter stages of sleep and arousals is far from convincing. Instead, it appears that hypoxia has a far wider effect upon sleep at altitude than was previously thought. A number of new approaches to the treatment of sleep disturbance at altitude have recently been identified. Whereas some treat the underlying hypoxia through pharmacological or technological means, others seek to address the symptoms of sleep disturbance more directly. Summary Many of the current approaches to treating sleep disturbance at altitude have been shown to be well tolerated and successful, although few comparisons have been made. Future research is likely to focus upon matching the safest and most successful approach to the individual and their environment.

We present a randomised, controlled, crossover trial of the Caudwell Xtreme Everest (CXE) closed circuit breathing system vs an open circuit and ambient air control in six healthy, hypoxic volunteers at rest and exercise at Everest Base Camp, at 5300 m. Compared with control, arterial oxygen saturations were improved at rest with both circuits. There was no difference in the magnitude of this improvement as both circuits restored median (IQR [range]) saturation from 75%, (69.5-78.9 [68-80]%) to > 99.8% (p = 0.028). During exercise, the CXE closed circuit improved median (IQR [range]) saturation from a baseline of 70.8% (63.8-74.5 [57-76]%) to 98.8% (96.5-100 [95-100]%) vs the open circuit improvement to 87.5%, (84.1-88.6 [82-89]%; p = 0.028). These data demonstrate the inverse relationship between supply and demand with open circuits and suggest that ambulatory closed circuits may offer twin advantages of supplying higher inspired oxygen concentrations and/or economy of gas use for exercising hypoxic adults.

C. Raymond Greene (1901–1982) was a man of many talents. After graduating from medical school in 1927, he spent a decade in general practice. He subsequently became heavily involved in the emerging specialty of endocrinology and went on to gain considerable recognition in the treatment of thyroid disorders before eventually becoming involved in the world of medical publishing. Aside from Greene's mainstream vocational and intellectual pursuits, from boyhood he nurtured a passionate interest in mountaineering—first in his native Great Britain, and then the European Alps, and ultimately in the high Himalayas. His involvement in landmark climbs, such as the successful Kamet venture in 1931 and Everest attempt in 1933, earned him a place in the pantheon of Himalayan explorers and mountaineers and stimulated Green's interest in high altitude physiology and medicine. He made notable additions to the literature on this subject in publications such as Nature and Journal of Physiology . Apart from his remarkable life achievements in the areas of medicine, mountaineering, and publishing, Greene was perhaps best remembered by those close to him (and by contemporary readers who are devotees of his writing) as a peerless storyteller with a sardonic sense of irony.

Altitude illness can occur in anyone who ascends to high altitude. Better understanding of altitude illness is associated with a lower incidence of acute mountain sickness (AMS). The purpose of this study is to compare, for the first time, the incidence and understanding of altitude illness between foreign trekkers and indigenous porters in Nepal.Interviews and questionnaires were completed at the International Porter Protection Group Rescue Post at Machermo (4470 m). Participants completed the Lake Louise acute mountain sickness self-assessment questionnaire. They were also asked about their actions in response to high altitude illness scenarios as well as their perception of the vulnerability of porters vs trekkers to altitude illness. Ascent profile, age, gender, ethnic origin, and altitude of home residence were also obtained.Trekkers (n=131) had a significantly higher incidence of AMS (21% vs 8%) than porters (n=92; P.02). Lowland porters (whose home villages were below 3050 m, n=61) had a numerically higher, though not significantly different, incidence of AMS (10% vs 3%) compared to highland porters (n=31). The majority of trekkers and porters recognized the symptoms of altitude illness and the most appropriate action to be taken. Despite the lower incidence of AMS in porters, around half felt that they were at greater risk than trekkers.Porters had a lower incidence of AMS, which may be attributable to repeated ascents through the trekking season, or differences in reporting symptoms. Both trekkers and porters demonstrated appropriate knowledge of actions to be taken in response to altitude illness.

We describe a unique ambulatory closed circuit for delivering high fractions of inspired oxygen to an exercising user who does not require isolation from their environment. We describe the major components and their function and suggest potential applications for such a circuit. This circuit may benefit patients who are chronically dependant on oxygen, are unable to exercise due to hypoxia, or require oxygen supplementation at high altitude.

In the mountain environment sudden cardiac death (SCD) has been shown to be responsible for the deaths of up to 52% of downhill skiers and 30% of hikers. The majority of SCD's are precipitated by a ventricular arrhythmia. Although most are likely to result from structural abnormalities associated with conditions such as ischaemic heart disease, a small but significant number may be due to abnormalities in ion channel activity, commonly known as, "channelopathies". Channelopathies have the potential to lengthen the time between ventricular depolarisation and repolarisation that can result in prolongation of the corrected QT interval (QTc) and episodes of polymorphic ventricular tachycardia (PVT) and eventually, ventricular fibrillation. This review examines the factors that prolong the QTc interval in the mountain environment and outlines a practical framework for preventing the life threatening arrhythmias that are associated with this condition.

Michael Phelps Ward (1925–2005) (Figures 1 and 2) is perhaps best known to the public for his role as a team member of the 1951 Mount Everest Reconnaissance and participation in the successful 1953 first ascent of Everest. However, he was the holder of an enviable record of wider climbing and mountain exploration and an important pioneer in high-altitude/wilderness medicine as well. His busy professional life as a surgeon lasted until retirement from the UK’s National Health Service in 1993, after which he continued to work on high-altitude medical problems and, additionally, devote a great deal of time to researching the history of Central Asian exploration. Of the numerous articles and books Ward wrote, his 2003 book, Everest: A Thousand Years of Exploration,1 is perhaps his most distinctive work. This, his last book, stands as testimony to one man’s exceptional, multifaceted talents. This most unique work brings together the historical chronicle of Mount Everest’s mountaineering, geographical, and medical aspects into a definitive, coherent story. Ward was the son of an expatriate family; his father was a member of the Malayan Civil Service. Educated in England, Ward spent long periods separated from his parents because these were the days before routine transoceanic flights. In fact, his parents were in Singapore when the Japanese Imperial Army swept through this region in the early days of World War II. His mother just managed to get a place in one of the last boats leaving Singapore for Ceylon and eventually Great Britain, but his father was captured and interned by the Japanese for the duration of the war. His love affair with the mountains can be traced to a guided ascent of the Wetterhorn, in Switzerland, when he was 14 years old. From preparatory school, Ward went to Marlborough, where he spent the war years.

Zeolites have important industrial applications including use as catalysts, molecular sieves and ion exchange materials. In this study, three zeolite materials have been characterized by the National Institute of Standards and Technology (NIST) as reference materials (RMs): zeolite Y (RM 8850), zeolite A (RM 8851) and ZSM-5 zeolite (RM 8852). They have been characterized by a variety of chemical and physical measurement methods: X-ray fluorescence (XRF), gravimetry, instrumental neutron activation analysis (INAA), nuclear magnetic resonance (NMR), calorimetry, synchrotron X-ray diffraction, neutron diffraction, laser light extinction, laser light scattering, electric sensing zone, X-ray sedimentation, scanning transmission electron microscopy (STEM), scanning electron microscopy (SEM) and optical microscopy. The chemical homogeneity of the materials has been characterized. Reference values are given for the major components (major elements, loss on ignition [LOI] and loss on fusion [LOF]), trace elements and Si/Al and Na/Al ratios. Information values are given for enthalpies of formation, unit cell parameters, particle size distributions, refractive indices and variation of mass with variation in relative humidity (RH). Comparisons are made to literature unit cell parameters. The RMs are expected to provide a basis for intercomparison studies of these zeolite materials.

The high-altitude environment - Avalanches - Preparing to travel to altitude - Humans at altitude - High-altitude physiology - High-altitude illness - Children at altitude - Chronic mountain sickness

Despite the presence of a number of anecdotal reports in the mountaineering literature, mucociliary dysfunction at high altitude has received little scientific attention. However, the dry, cold, thin air at high altitude has the potential to undermine normal mucociliary function. This seems increasingly likely in mountaineers who also experience dehydration, nasal obstruction, and extremes of aerobic respiration when climbing in such environments. These factors may result in a number of clinical conditions that range from sore throats and coughs commonly seen at altitude to rarer cases of bronchiolar collapse and lung atelectasis. The purpose of this review is to discuss the etiology of mucociliary dysfunction at altitude and outline a number of potential solutions to the problems this phenomenon presents.

A C60+ primary ion source has been coupled to an ion microscope secondary ion mass spectrometry (SIMS) instrument to examine sputtering of silicon with an emphasis on possible application of C60+ depth profiling for high depth resolution SIMS analysis of silicon semiconductor materials. Unexpectedly, C60+ SIMS depth profiling of silicon was found to be complicated by the deposition of an amorphous carbon layer which buries the silicon substrate. Sputtering of the silicon was observed only at the highest accessible beam energies (14.5 keV impact) or by using oxygen backfilling. C60+ SIMS depth profiling of As delta-doped test samples at 14.5 keV demonstrated a substantial (factor of 5) degradation in depth resolution compared to Cs+ SIMS depth profiling. This degradation is thought to result from the formation of an unusual platelet-like grain structure on the SIMS crater bottoms. Other unusual topographical features were also observed on silicon substrates after high primary ion dose C60+ bombardment.

Contagious bovine pleuropneumonia (CBPP) caused by the Mycoplasma mycoides subspecies mycoides SC is one of the major plagues affecting cattle. With the imminent eradication of rinderpest from Africa, CBPP will become the major epidemic disease on the continent, because the majority of countries in sub-Saharan Africa have the infection in their cattle. There is an enclave of CBPP on the borders of Angola, Botswana, Namibia, and Zambia. There has been endemic infection in the cattle herds on the borders of Angola and Namibia for more than 100 years, with irregular spread from these animals to the cattle of Botswana or Zambia. However, much of Angola and Namibia and all of Botswana and Zambia are currently free from the disease. This paper explains the origins of the problem and describes the current disease situation. A plan for the eradication of CBPP from this area is proposed and discussed. If this plan is successful it will release valuable resources to tackle other constraints on livestock and food production. Furthermore, it will act as a model for the eradication of CBPP from the remainder of the continent.

Two days before the first ascent of Mt. Everest in 1953, Tom Bourdillon and Charles Evans climbed to within 90 m of the summit at unprecedented speeds. By breathing pure oxygen from a closed circuit, the pair were able to obtain an enormous physiological advantage. Unfortunately, due to a malfunction in Evans's circuit, the pair abandoned their attempt on the South Summit. For many who used the circuit in the 1930s and 1950s, the device proved too heavy, uncomfortable, and tiring for mountaineering. These factors, together with the wider ethical concerns of using supplemental oxygen at altitude, have meant that closed-circuit oxygen has been ignored for more than 50 years. In this article the authors will attempt to describe the history of this discarded circuit and the experience of those who utilized it.

High altitude commercial expeditions are increasingly popular. As high altitude illnesses are common on ascent to altitude, this study aimed to ascertain whether medications for these conditions were carried by commercial operators who run high altitude expeditions. Despite recommendations, it appears that drugs to treat high altitude illnesses are not routinely carried by commercial operators.

Copper oxide has been detected in the copper containing alloys of NBS Standard Reference Material (SRM) 482. This occurrence is significant because it represents heterogeneity within a standard reference material that was certified to be homogeneous on a micrometer scale. Oxide occurs as elliptically to spherically shaped precipitates whose size differs with alloy composition. The largest precipitates occur in the Au20-Cu80 alloy and range in size from submicrometer up to 2 μm in diameter. Precipitates are observed using light microscopy, electron microscopy, and secondary ion mass spectrometry (SIMS). SIMS has demonstrated that the precipitates are present within all the SRM 482 wires that contain copper. Only the pure gold wire is precipitate free. Initial results from the analysis of the Au20-Cu80 alloy indicate that the percentage of precipitates is less than 1 % by area. Electron probe microanalysis (EPMA) of large (2 μm) precipitates in this same alloy indicates that precipitates are detectable by EPMA and that their composition differs significantly from the certified alloy composition. The small size and low percentage of these oxide precipitates minimizes the impact that they have upon the intended use of this standard for electron probe microanalysis. Heterogeneity caused by these oxide precipitates may however preclude the use of this standard for automated EPMA analyses and other microanalysis techniques.

At the end of WW II, the British Government of the time decided that it was essential for Britain to become self-sufficient in food. In consequence there was a large investment in services to agriculture and in particular many new veterinary investigation centers were opened to help farmers produce more animal products. The upsurge in world trade led the Government of Mrs. Thatcher to decide that livestock was just another commodity and so there has been a massive scaling down of money available to assist the livestock farmer. For Botswana the livestock industry is vital to the well-being of the people and successive Governments have continued to invest in veterinary services. As a consequence, Botswana has one of the best and most efficient Veterinary Services in Africa. By contrast, the livestock industry in Peru has an insignificant effect on the gross national product. The fiber exports from camelids are a small international market, while the dairy industry is unable to provide sufficient milk for the nation. Partly as a result of this, the Peruvian Government invests very little in the livestock industry or the veterinary services that support it. Vietnam is in a transitional stage: there is a large but as yet unorganized livestock industry with a mass of smallholder farmers. The Government has made a large investment in people in the Department of Animal Health but without a concomitant investment in equipment and training. If the industry is to develop, it will require much more investment from the government. These countries will be discussed in more detail and an attempt will be made to show how by relating the services to the livestock industry, governments can improve services and at the same time cut the costs.

A simple ashing procedure for a mixture containing kaolinite and chrysotile is described that converts kaolinite to amorphous metakaolinite while retaining the diffraction intensity of chrysotile. This ashing procedure removes the X-ray diffraction (XRD) pattern overlap between kaolinite and chrysotile that can interfere with the analysis of even high concentrations of chrysotile. Samples are ashed at 460 °C in a muffle furnace for 40 h to completely convert kaolinite to metakaolinite. The complete conversion of 1 g of kaolinite under these conditions was determined for two standard kaolinite samples from Georgia, KGa-1 and KGa-2. Two of the most common types of commercial chrysotile, long-fiber Canadian and short-fiber Californian chrysotile, are demonstrated to retain diffraction intensity after ashing at 460 °C. Both chrysotile samples have the same integrated intensity for the (002) reflection prior to ashing, although the peak breadths for the two samples are quite different. Ashing at 480 and 500 °C reduces the diffraction intensities of both chrysotile samples by 15%, and broadens the peaks by approximately 3%. Using the prescribed ashing procedure and x-ray diffraction with an internal corundum standard, two kaolinite-bearing building materials containing chrysotile near 0.01 mass fraction were analyzed. The ashing procedure has additional advantages in reducing some samples to powders and removing volatile components, thereby eliminating some sample preparation procedures and concentrating any chrysotile present in the sample. The removal of volatile components improves the sensitivity of XRD analysis to concentrations below 0.01 mass fraction chrysotile.

The incidence of acute mountain sickness can be reduced by ascending slowly to altitude. We compared a recommended ascent rate with those offered by commercial companies to three of the most popular high-altitude destinations in the world. While the majority complied with the recommended ascent rate, ascents on Kilimanjaro did not.

The Wilderness Medical Society convened an expert panel to develop evidence-based guidelines for the management of pain in austere environments. Recommendations are graded on the basis of the quality of supporting evidence as defined by criteria put forth by the American College of Chest Physicians. This is an updated version of the original WMS Practice Guidelines for the Treatment of Acute Pain in Remote Environments published in Wilderness & Environmental Medicine 2014;25(1):41–49.

Drag reduction of road vehicles continues to be the holy grail of aerodynamicists with renewed importance of aerodynamics as OEMs strive to reduce CO2 and improve fuel economy. New legislation such as Worldwide harmonized Light vehicles Test Procedure (WLTP) is increasing the emphasis on real world boundary conditions (with moving ground wind tunnel testing) and vehicle configurations, in an effort to obtain more realistic fuel consumption figures. However, WLTP in common with all other drive cycles used in the automotive sector is based on zero-yaw aerodynamic measurements. This implicitly assumes conditions vehicles rarely see: the onset wind vector is at zero yaw, the atmosphere is still and undisturbed by other road users. This paper will show that many modern cars (particularly low drag saloon cars) have noticeable drag coefficient (CD) minima at zero yaw, with some having up to 10% increase in CD for relatively small yaw angle changes around zero. The concept of wind averaged drag (CDW) will be discussed as a means of assessing real world aerodynamic performance. Three methods of calculating CDW are investigated and the MIRA method is preferred for application to passenger cars. This demonstrates that including yaw angle effects via CDW provides a significantly different perspective on the aerodynamic contribution to fuel economy.

Academic research has been scant with regard to examining the impact of leadership on telecentre sustainability. This chapter evolved from the e-Sri Lanka program funded by the World Bank as a unique South Asian project, which has seen the establishment of a network of 765 Nenasala telecentres, both grass-root non-profit and for-profit enterprises as its main interface with the community. This context provided an interesting avenue in which to examine different leadership models in the digital age. Through comprehensive analysis of archival material, focus group data from Nenasala operators, and interview data from stakeholders in Sri Lanka, the findings reveal that leadership was key to Nenasala telecentre sustainability and success at the telecentre organisation level. The researchers find that one of the models, the special community-based leadership model adopted by Sri Lankan Nenasalas as a Socio-Cultural Leadership (SCL) approach prevalent in Sri Lankan not-for-profit Nenasala telecentres, successfully enhanced sustainability through community focus and demonstrated competitive advantage over their for-profit telecentre counterparts. These findings suggest that a replication of the study in other developing countries could prove to be invaluable.

Damage to the teeth during general anaesthesia is a frequent cause of morbidity for patients and a source of litigation against anaesthetists. Most injuries occur as a result of laryngoscopy. The use of an oropharyngeal airway as a bite block can increase the risk of dental damage and should be avoided. Bite blocks should be made from an appropriate material and placed between molar teeth rather than incisors. Patients should be advised about the possibility of dental trauma during anaesthesia and should be advised to have preoperative dental treatment to minimize dental factors that increase the risk of injury. Children in a mixed dentition phase (between the ages of about 5–12 years) are a high-risk group. Anaesthetic departments should have local protocols to refer patients for dental treatment postoperatively in the event of trauma.

On October 24, 1981, Chris Pizzo and Yong Tenzing, members of the American Medical Research Expedition to Mt Everest (AMREE), stood on the highest point on earth and collected 6 alveolar gas samples. These, together with further data collected from the South Col (8050 m), provided the foundations for what is surely one of the most unique field experiments ever undertaken—the calculation of arterial blood gases from a mountaineer on the summit of Mt Everest (8848 m; Table). Without the accurate portable blood gas analyzers that many of us now take for granted, the AMREE team used the ‘‘Bohr Integration,’’ a complex computational method used primarily to calculate the diffusion capacity of oxygen inside the human lungs. By assuming this value, the AMREE team was able to calculate the mean alveolar-capillary PO2 difference and therefore deduce the PO2 of arterial blood. However, to complete this, a long list of measurements and assumptions would need to be made first, and it is this attention to detail that makes ‘‘Pulmonary Gas Exchange on the Summit of Mt Everest’’ such an exceptional piece of work.1 In what Edouard Wyss Dunant, the leader of the unsuccessful 1952 Swiss Expedition to Mt Everest, once described as the ‘‘todeszone’’ or ‘‘death zone,’’ the AMREE team conducted an unparalleled set of tests. Not only did they record the first accurate barometric pressure reading on the summit of Mt Everest, but they were also able to obtain 42 resting alveolar gas samples from various sites above 8000 m (Figure 1). These results showed, for the first time, the dramatic fall in alveolar

Contagious bovine pleuropneumonia (CBPP) caused by Mycoplasma mycoides subspecies mycoides small colony (M. mycoides) has been endemic in many parts of Africa for the greater part of this century. Because of an international vaccination campaign the disease was almost eliminated from the continent. With the deteriorating economic situation of many countries, vaccination programs have been allowed to slip; drought conditions have resulted in great movements of livestock and the disease has spread rapidly to the east and south. For Government Veterinary Departments, the implications of this resurgence of CBPP, are serious. The costs threaten to overwhelm completely under-funded government services. Where cost-recovery measures are introduced, the charging for vaccines may damage rapport with communities and erode the credibility of the government services. Farmers may find the loss of cattle and the costs of vaccine severe burdens which threaten their livelihoods and social well-being (Zambia) and even, in extreme cases, their survival (Botswana). Controlling the disease today presents new possibilities which include increased cross-border collaboration (Malawi/Tanzania), increased emphasis on monitoring (N. Zambia) and the greater involvement of communities in disease control (W. Zambia).

Understanding risks faced by firms and their reactions in response to those risks requires analysis of the ambiguities inherent in human behaviour. Yet, evidence from two case studies on investment and insurance professionals in the finance industry suggest that more focus on human capital may be prudent in reducing epistemic uncertainty particularly considering recent events in which the investing public has had a crisis of confidence in corporate leaders. It is particularly appropriate for regulators to provide a context in which market participants exercise due diligence by ensuring human capital is enhanced by as much knowledge as possible where more human capital knowledge could reduce both risk in investments and insurance, ultimately challenging the sustainability of organisations during periods of epistemic uncertainty. This paper suggests that investment analysts, fund managers and insurance professionals lack the appropriate competencies, skills, knowledge and abilities required to meet the demands of the analysis of human capital in relation to understanding risk. Such competencies include disciplinary knowledge of sustainable human resource management and organisational change systems and their links to corporate performance and risk mitigation. An alignment with human resource management (HRM/ HR) that is equally focused on internal and external risk is of strategic importance for such professionals and their organisations in human capital risk mitigation.

Contagious bovine pleuropneumonia (CBPP) is one of the major threats to cattle health and production in Africa. This article reviews the clinical manifestations, lesions and epidemiology of the disease. The clinical manifestations and lesions are typical and are no different in Africa from those seen in other countries. CBPP is a respiratory disease characterised by pneumonia and serofibrinous pleurisy. The usual form of this disease is acute but chronic forms are frequent, particularly in endemic regions. Hyperacute forms, with a high mortality rate, can be seen at the beginning of outbreaks in newly infected regions. The epidemiology of the disease in Africa is dominated by four factors, namely: cattle are the only species affected, there is no reservoir in wild animals, clinical cases or chronic carriers are the usual sources of infection, through direct contact, and cattle movements play a very important role in the maintenance and extension of the disease. CBPP is widespread in Africa and, according to the Office International des Epizooties and to various reports in 1995, the disease is present in 24 countries of tropical Africa. In western Africa, CBPP is mainly enzootic or sporadic but in some countries the incidence is increasing. The situation in Central Africa is not very alarming. However, in eastern and south-eastern Africa, CBPP has become a major issue, placing southern Africa under direct threat. An evaluation of economic losses due to the disease and the cost-benefit ratio of control programmes is indispensable, since such economic assessments are needed before policy-makers decide on programmes of control or eradication. This is an area which needs to be addressed immediately, as the launching of new campaigns, particularly in eastern and southern Africa, is urgently needed.

To the Editor: We were interested to read the tragic case report in which an individual died after avalanche burial with an active heart rate recording device.1 Individuals have been resuscitated from core temperatures as low as 19°C after avalanche burial.2 Rescuers are advised to exercise care when handling casualties because of the risk of triggering ventricular arrhythmias, although the …

We present a randomised, controlled, crossover trial of the Caudwell Xtreme Everest (CXE) closed circuit breathing system vs an open circuit and ambient air control in six healthy, hypoxic volunteers at rest and exercise at Everest Base Camp, at 5300 m. Compared with control, arterial oxygen saturations were improved at rest with both circuits. There was no difference in the magnitude of this improvement as both circuits restored median (IQR [range]) saturation from 75%, (69.5-78.9 [68-80]%) to99.8% (p = 0.028). During exercise, the CXE closed circuit improved median (IQR [range]) saturation from a baseline of 70.8% (63.8-74.5 [57-76]%) to 98.8% (96.5-100 [95-100]%) vs the open circuit improvement to 87.5%, (84.1-88.6 [82-89]%; p = 0.028). These data demonstrate the inverse relationship between supply and demand with open circuits and suggest that ambulatory closed circuits may offer twin advantages of supplying higher inspired oxygen concentrations and/or economy of gas use for exercising hypoxic adults.