Detection of Artemisinin Resistance Marker Kelch-13 469Y in Plasmodium falciparum, South Kivu, Democratic Republic of the Congo, 2022.

Partial artemisinin resistance has emerged in East Africa, posing a threat to malaria control across the continent. The Democratic Republic of the Congo carries one of the heaviest malaria burdens globally, and the South Kivu province directly borders current artemisinin resistance hot spots, but indications of such resistance have not been observed so far. We assessed molecular markers of antimalarial drug resistance in 256 Plasmodium falciparum isolates collected in 2022 in South Kivu, Democratic Republic of the Congo. One isolate carried the P. falciparum Kelch-13 469Y variant, a marker associated with partial artemisinin resistance and decreased lumefantrine susceptibility in Uganda. In addition, the multidrug resistance-1 mutation pattern suggested increased lumefantrine tolerance.

Prevalence of Falciparum and non-Falciparum Malaria in the 2014-15 Rwanda Demographic Health Survey.

Background: Malaria remains a major cause of morbidity in sub-Saharan Africa. Undetected asymptomatic falciparum malaria results in a large transmission reservoir and there is evidence of increasing non-falciparum malaria as malaria is controlled in Africa, both resulting in challenges for malaria control programs. Methods: We performed quantitative real time PCR for 4 malaria species in 4,596 individuals from the 2014-2015 Rwanda Demographic Health Survey. Bivariate models were used to determine species-specific associations with risk factors. Results: Asymptomatic falciparum malaria, P. ovale spp., and P. malariae infection had broad spatial distribution across Rwanda. P. vivax infection was rare. Overall infection prevalence was 23.6% (95%CI [21.7%, 26.0%]), with falciparum and non-falciparum at 17.6% [15.9%, 19.0%] and 8.3% [7.0%, 10.0%], respectively. Parasitemias tended to be low and mixed species infections were common, especially where malaria transmission was the highest. Falciparum infection was associated with socio-econiomic status, rural residence and low altitude. Few risk factors were associated with non-falciparum malaria. Conclusions: Asymptomatic falciparum malaria and non-falciparum malaria are common and widely distributed across Rwanda. Continued molecular monitoring of Plasmodium spp. is needed to monitor these threats to malaria control in Africa.

Avoid equipment graveyards: rigorous process to improve identification and procurement of effective, affordable, and usable newborn devices in low-resource hospital settings.

BACKGROUND: Millions of newborns die annually from preventable causes, with the highest rates occurring in Africa. Reducing neonatal mortality requires investment to scale hospital care, which includes providing hospitals with appropriate technology to care for small and sick newborns. Expensive medical devices designed for high-resource settings often fail to withstand conditions in low-resource hospitals, including humidity, dust, frequent user turnover, complex maintenance, lack of stable power, or difficulty sourcing expensive consumables. Rigorous evaluation protocols are needed to identify effective, affordable, rugged, and easy-to-use medical devices appropriate for quality hospital-based newborn care in low-resource hospitals. METHODS: We developed an evidence-based technology review process to identify medical devices suitable for small and sick newborn care in low-resource hospitals. The eight-step process consists of: identifying devices needed for effective newborn care; defining Target Product Profiles (TPPs); identifying commercially-available products that may meet TPPs; conducting desk research to evaluate technologies against TPPs; performing technical performance verification testing under laboratory conditions; verifying technical performance after exposure to heat, humidity, dust, and power loss; performing usability evaluations with nurses, and qualifying devices that pass all steps. Devices were purchased, installed, and monitored in newborn wards across Kenya, Malawi, Nigeria, and Tanzania. RESULTS: Of 271 devices considered, only 45 (16.6%) met corresponding TPPs based on desk research. Thirty-nine were purchased and evaluated in the laboratory; five (12.8%) failed to meet TPPs. Thirty-four products passing laboratory evaluation underwent short-term environmental testing; only one (2.9%) device failed. Thirty-seven products underwent usability testing with 127 clinicians; surprisingly, 14 (37.8%) failed to meet TPPs. Twenty-three products passed all evaluations, and 2457 devices were installed across 65 newborn wards in Kenya, Malawi, Nigeria, and Tanzania. Continuous device monitoring reported minimal device failures, with failed devices typically returned to service within two days, resulting in an average uptime (service days divided by days installed) of 99%. CONCLUSION: An evidence-based device selection process can improve procurement of effective, affordable, rugged, usable newborn care devices for low-resource hospitals, and feedback to manufacturers can improve device quality. Similar processes could be adapted beyond newborn care to identify medical devices suitable for implementation in any low-resource setting.

Target product profiles for neonatal care devices: systematic development and outcomes with NEST360 and UNICEF.

BACKGROUND: Medical devices are critical to providing high-quality, hospital-based newborn care, yet many of these devices are unavailable in low- and middle-income countries (LMIC) and are not designed to be suitable for these settings. Target Product Profiles (TPPs) are often utilised at an early stage in the medical device development process to enable user-defined performance characteristics for a given setting. TPPs can also be applied to assess the profile and match of existing devices for a given context. METHODS: We developed initial TPPs for 15 newborn product categories for LMIC settings. A Delphi-like process was used to develop the TPPs. Respondents completed an online survey where they scored their level of agreement with each of the proposed performance characteristics for each of the 15 devices. Characteristics with < 75% agreement between respondents were discussed and voted on using Mentimeter™ at an in-person consensus meeting. FINDINGS: The TPP online survey was sent to 180 people, of which 103 responded (57%). The majority of respondents were implementers/clinicians (51%, 53/103), with 50% (52/103) from LMIC. Across the 15 TPPs, 403 (60%) of the 668 performance characteristics did not achieve > 75% agreement. Areas of disagreement were voted on by 69 participants at an in-person consensus meeting, with consensus achieved for 648 (97%) performance characteristics. Only 20 (3%) performance characteristics did not achieve consensus, most (15/20) relating to quality management systems. UNICEF published the 15 TPPs in April 2020, accompanied by a report detailing the online survey results and consensus meeting discussion, which has been viewed 7,039 times (as of January 2023). CONCLUSIONS: These 15 TPPs can inform developers and enable implementers to select neonatal care products for LMIC. Over 2,400 medical devices and diagnostics meeting these TPPs have been installed in 65 hospitals in Nigeria, Tanzania, Kenya, and Malawi through the NEST360 Alliance. Twenty-three medical devices identified and qualified by NEST360 meet nearly all performance characteristics across 11 of the 15 TPPs. Eight of the 23 qualified medical devices are available in the UNICEF Supply Catalogue. Some developers have adjusted their technologies to meet these TPPs. There is potential to adapt the TPP process beyond newborn care.

Devices and furniture for small and sick newborn care: systematic development of a planning and costing tool.

BACKGROUND: High-quality neonatal care requires sufficient functional medical devices, furniture, fixtures, and use by trained healthcare workers, however there is lack of publicly available tools for quantification and costing. This paper describes development and use of a planning and costing tool regarding furniture, fixtures and devices to support scale-up of WHO level-2 neonatal care, for national and global newborn survival targets. METHODS: We followed a systematic process. First, we reviewed planning and costing tools of relevance. Second, we co-designed a new tool to estimate furniture and device set-up costs for a default 40-bed level-2 neonatal unit, incorporating input from multi-disciplinary experts and newborn care guidelines. Furniture and device lists were based off WHO guidelines/norms, UNICEF and national manuals/guides. Due to lack of evidence-based quantification, ratios were based on operational manuals, multi-country facility assessment data, and expert opinion. Default unit costs were from government procurement agency costs in Kenya, Nigeria, and Tanzania. Third, we refined the tool by national use in Tanzania. RESULTS: The tool adapts activity-based costing (ABC) to estimate quantities and costs to equip a level-2 neonatal unit based on three components: (1) furniture/fixtures (18 default but editable items); (2) neonatal medical devices (16 product categories with minimum specifications for use in low-resource settings); (3) user training at device installation. The tool was used in Tanzania to generate procurement lists and cost estimates for level-2 scale-up in 171 hospitals (146 District and 25 Regional Referral). Total incremental cost of all new furniture and equipment acquisition, installation, and user training were US$93,000 per District hospital (level-2 care) and US$346,000 per Regional Referral hospital. Estimated cost per capita for whole-country district coverage was US$0.23, representing 0.57% increase in government health expenditure per capita and additional 0.35% for all Regional Referral hospitals. CONCLUSION: Given 2.3 million neonatal deaths and potential impact of level-2 newborn care, rational and efficient planning of devices linked to systems change is foundational. In future iterations, we aim to include consumables, spare parts, and maintenance cost options. More rigorous implementation research data are crucial to formulating evidence-based ratios for devices numbers per baby. Use of this tool could help overcome gaps in devices numbers, advance efficiency and quality of neonatal care.

Improved screening of retinopathy of prematurity (ROP): development of a target product profile (TPP) for resource-limited settings.

BACKGROUND: As more preterm infants survive, complications of preterm birth, including retinopathy of prematurity (ROP), become more prevalent. ROP rates and blindness from ROP are higher in low-income and middle-income countries, where exposure to risk factors can be higher and where detection and treatment of ROP are under-resourced or non-existent. Access to low-cost imaging devices would improve remote screening capabilities for ROP. METHODS: Target product profiles (TPPs) are developed early in the medical device development process to define the setting, target user and range of product requirements. A Delphi-like process, consisting of an online survey and consensus meeting, was used to develop a TPP for an ROP imaging device, collecting feedback on a proposed set of 64 product requirements. RESULTS: Thirty-six stakeholders from 17 countries provided feedback: clinicians (72%), product developers (14%), technicians (6%) and other (8%). Thirty-six per cent reported not currently screening for ROP, with cited barriers including cost (44%), no training (17%) and poor image quality (16%). Among those screening (n=23), 48% use more than one device, with the most common being an indirect ophthalmoscope (87%), followed by RetCam (26%) and smartphone with image capture (26%). Consensus was reached on 53 (83%) product requirements. The 11 remaining were discussed at the consensus meeting, and all but two achieved consensus. CONCLUSIONS: This TPP process was novel in that it successfully brought together diverse stakeholders to reach consensus on the product requirements for an ROP imaging devices. The resulting TPP provides a framework from which innovators can develop prototypes.

Cost Drivers of Endothelial Keratoplasty: A Time-Driven Activity-Based Costing Analysis.

PURPOSE: To determine cost drivers of endothelial keratoplasty (EK) through evaluation of surgical costs and procedure length based on type of EK, use of preloaded grafts, and performance of simultaneous cataract surgery. DESIGN: This study was an economic analysis of EKs at a single academic institution using time-driven activity-based costing (TDABC) methodology. PARTICIPANTS: Endothelial keratoplasty surgical cases, including Descemet membrane endothelial keratoplasty (DMEK) and Descemet stripping automated endothelial keratoplasty (DSAEK), at the University of Michigan Kellogg Eye Center from 2016 to 2018 were included in the analysis. METHODS: Data and inputs were obtained via the electronic health record (EHR) and from prior literature. Simultaneous cataract surgeries were included and separately categorized for analysis. Endothelial keratoplasty expenses were determined with TDABC, a method for cost calculation that incorporates the time that key resources are used and each resource's associated cost rate. MAIN OUTCOME MEASURES: Main outcome measures included surgery length (in minutes) and day-of-surgery costs. RESULTS: There were 559 EKs included: 355 DMEKs and 204 DSAEKs. Fewer DSAEKs had simultaneous cataract extraction (47; 23%) than DMEK (169; 48%). Of the DMEKs, 196 (55%) used preloaded corneal grafts. Descemet membrane endothelial keratoplasty cost $392.31 less (95% confidence interval, $251.05-$533.57; P < 0.0001) than DSAEK and required 16.94 fewer minutes (14.16-19.73; P < 0.0001). Descemet membrane endothelial keratoplasty cases that used preloaded corneal grafts cost $460.19 less ($316.23-$604.14; P < 0.0001) and were 14.16 minutes shorter (11.39-16.93; P < 0.0001). In multivariate regression, preloaded graft use saved $457.19, DMEK (compared with DSAEK) saved $349.97, and simultaneous cataract surgery added $855.17 in day-of-surgery costs. CONCLUSIONS: Cost analysis of TDABC identified a day-of-surgery cost and surgical time reduction associated with the use of preloaded grafts for DMEK, DMEK compared with DSAEK, and isolated EK compared with EK combined with cataract surgery. This study provides an improved understanding of surgical cost drivers and margin incentivization, which may explain trends and indirectly influence patient care decisions in cornea surgery practices. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Examining the Early Distribution of the Artemisinin-Resistant Plasmodium falciparum kelch13 R561H Mutation in Areas of Higher Transmission in Rwanda.

Background: Artemisinin resistance mutations in Plasmodium falciparum kelch13 (Pfk13) have begun to emerge in Africa, with Pfk13-R561H being the first reported in Rwanda in 2014, but limited sampling left questions about its early distribution and origin. Methods: We genotyped P. falciparum positive dried blood spot (DBS) samples from a nationally representative 2014-2015 Rwanda Demographic Health Surveys (DHS) HIV study. DBS were subsampled from DHS sampling clusters with >15% P. falciparum prevalence, as determined by rapid testing or microscopy done during the DHS study (n clusters = 67, n samples = 1873). Results: We detected 476 parasitemias among 1873 residual blood spots from a 2014-2015 Rwanda Demographic Health Survey. We sequenced 351 samples: 341/351 were wild-type (97.03% weighted), and 4 samples (1.34% weighted) harbored R561H that were significantly spatially clustered. Other nonsynonymous mutations found were V555A (3), C532W (1), and G533A (1). Conclusions: Our study better defines the early distribution of R561H in Rwanda. Previous studies only observed the mutation in Masaka as of 2014, but our study indicates its presence in higher-transmission regions in the southeast of the country at that time.

Is there a "price that's right" for at-home COVID tests?

The COVID-19 pandemic has impacted the daily lives of individuals across the world as multiple variants continue introducing new complexities. In December 2021, which is when we conducted our study, pressure to resume the normalcy of daily life was mounting as a new variant, Omicron, was rapidly spreading. A variety of at-home tests detecting SARS-CoV-2, known to the general public as "COVID tests," were available for consumers to purchase. In this study, we conducted conjoint analysis utilizing an internet-based survey by presenting consumers (n = 583) with 12 different hypothetical at-home COVID test concepts that varied on five attributes (price, accuracy, time, where-to-buy, and method). Price was identified as the most important attribute, because participants were very price sensitive. Quick turnaround time and high accuracy were also identified as important. Additionally, although 64% of respondents were willing to take an at-home COVID test, only 22% reported they had previously taken the test. On December 21, 2021, President Biden announced the U.S. government would purchase 500 million at-home rapid tests and distribute them for free to Americans. Given the importance of price to participants, this policy of providing free at-home COVID tests was directionally appropriate.

What Determines Paternity in Wild Lizards? A Spatiotemporal Analysis of Behavior and Morphology.

Mating behavior in animals can be understood as a sequence of events that begins with individuals encountering one another and ends with the production of offspring. Behavioral descriptions of animal interactions characterize early elements of this sequence, and genetic descriptions use offspring parentage to characterize the final outcome, with behavioral and physiological assessments of mates and mechanisms of copulation and fertilization comprising intermediate steps. However, behavioral and genetic descriptions of mating systems are often inconsistent with one another, complicating expectations for crucial aspects of mating biology, such as the presence of multiple mating. Here, we use behavioral and genetic data from a wild population of the lizard Anolis cristatellus to characterize female multiple mating and the potential for sexual selection through female mate choice in this species. We find that 48% of sampled females bore offspring sired by multiple males. Moreover, spatiotemporal proximity between males and females was associated with whether a male sired a female's offspring, and if yes, how many offspring he sired. Additionally, male body size, but not display behavior, was associated with reproductive outcomes for male-female pairs. While much remains to be learned about the mechanisms of mating and targets of sexual selection in A. cristatellus, it is clear that female multiple mating is a substantial component of this species' mating system in nature.

The cascading effects of human food on hibernation and cellular aging in free-ranging black bears.

Human foods have become a pervasive subsidy in many landscapes, and can dramatically alter wildlife behavior, physiology, and demography. While such subsidies can enhance wildlife condition, they can also result in unintended negative consequences on individuals and populations. Seasonal hibernators possess a remarkable suite of adaptations that increase survival and longevity in the face of resource and energetic limitations. Recent work has suggested hibernation may also slow the process of senescence, or cellular aging. We investigated how use of human foods influences hibernation, and subsequently cellular aging, in a large-bodied hibernator, black bears (Ursus americanus). We quantified relative telomere length, a molecular marker for cellular age, and compared lengths in adult female bears longitudinally sampled over multiple seasons. We found that bears that foraged more on human foods hibernated for shorter periods of time. Furthermore, bears that hibernated for shorter periods of time experienced accelerated telomere attrition. Together these results suggest that although hibernation may ameliorate cellular aging, foraging on human food subsidies could counteract this process by shortening hibernation. Our findings highlight how human food subsidies can indirectly influence changes in aging at the molecular level.

Autologous blood transfusion in dogs with thoracic or abdominal hemorrhage: 25 cases (2007-2012).

OBJECTIVE: To describe the use and outcome following autologous blood transfusion (ABT) in dogs. DESIGN: Retrospective study (January 2007-July 2012). SETTING: Private veterinary referral center. ANIMALS: Twenty-five dogs that underwent ABT secondary to thoracic or abdominal hemorrhage. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The hospital transaction database was searched using the keyword "autotransfusion" from January 2007 to July 2012. Data collected included signalment, body weight, etiology of hemorrhage, source and method of collection, volumes and method of ABT administration, use of anticoagulant, reported complications, and outcome. Twenty-five dogs were included for a total of 27 ABTs. Causes of hemorrhage included vascular trauma (14/25 dogs, 56%), ruptured tumor (8/25, 32%), and coagulopathy attributed to brodifacoum toxicosis (3/25, 12%). Autologous blood was collected from the abdominal (19/25, 76%), thoracic (5/25, 20%), or abdominal and thoracic cavities (1/25, 4%). Anticoagulant was added to the ABT blood in 13 of 25 (52%) cases. A median ABT volume of 29.3 mL/kg (range 2.9-406.9 mL/kg) was infused through either a 210 µm blood administration filter (21/27, 78%) or an 18 µm hemonate filter (6/27, 22%). Reported complications that may have been associated with ABT included hypocalcemia (4/17, 24%), hemolyzed serum (5/19, 26%), and prolonged coagulation times (4/5, 80%). These complications were considered of minimal clinical significance. Additional blood products were administered in 17 of 25 (68%) dogs. Seventeen (68%) dogs survived to discharge. Cause of death in the remaining cases was euthanasia or cardiac arrest secondary to uncontrollable hemorrhage. CONCLUSIONS: ABT is an adjunct to volume replacement in dogs with thoracic or abdominal hemorrhage secondary to vascular trauma, ruptured tumor, or anticoagulant rodenticide toxicosis. ABT may be used as bridge to definitive hemorrhage control, particularly when other blood products are not available or affordable. Complications may include hypocalcemia, prolonged coagulation times, and hemolysis.

Examining the uncertain origin and management role of martens on Prince of Wales Island, Alaska.

Conservation biologists are generally united in efforts to curtail the spread of non-native species globally. However, the colonization history of a species is not always certain, and whether a species is considered non-native or native depends on the conservation benchmark. Such ambiguities have led to inconsistent management. Within the Tongass National Forest of Alaska, the status of American marten (Martes americana) on the largest, most biologically diverse and deforested island, Prince of Wales (POW), is unclear. Ten martens were released to POW in the early 1930s, and it was generally believed to be the founding event, although this has been questioned. The uncertainty surrounding when and how martens colonized POW complicates management, especially because martens were selected as a design species for the Tongass. To explore the history of martens of POW we reviewed other plausible routes of colonization; genetically and isotopically analyzed putative marten fossils deposited in the late Pleistocene and early Holocene to verify marten occupancy of POW; and used contemporary genetic data from martens on POW and the mainland in coalescent simulations to identify the probable source of the present-day marten population on POW. We found evidence for multiple routes of colonization by forest-associated mammals beginning in the Holocene, which were likely used by American martens to naturally colonize POW. Although we cannot rule out human-assisted movement of martens by Alaskan Natives or fur trappers, we suggest that martens be managed for persistence on POW. More generally, our findings illustrate the difficulty of labeling species as non-native or native, even when genetic and paleo-ecological data are available, and support the notion that community resilience or species invasiveness should be prioritized when making management decisions rather than more subjective and less certain conservation benchmarks.

Magnesium physiology and clinical therapy in veterinary critical care.

OBJECTIVE: To review magnesium physiology including absorption, excretion, and function within the body, causes of magnesium abnormalities, and the current applications of magnesium monitoring and therapy in people and animals. ETIOLOGY: Magnesium plays a pivotal role in energy production and specific functions in every cell in the body. Disorders of magnesium can be correlated with severity of disease, length of hospital stay, and recovery of the septic patient. Hypermagnesemia is seen infrequently in people and animals with significant consequences reported. Hypomagnesemia is more common in critically ill people and animals, and can be associated with platelet, immune system, neurological, and cardiovascular dysfunction as well as alterations in insulin responsiveness and electrolyte imbalance. DIAGNOSIS: Measurement of serum ionized magnesium in critically or chronically ill veterinary patients is practical and provides information necessary for stabilization and treatment. Tissue magnesium concentrations may be assessed using nuclear magnetic resonance spectroscopy as well as through the application of fluorescent dye techniques. THERAPY: Magnesium infusions may play a therapeutic role in reperfusion injury, myocardial ischemia, cerebral infarcts, systemic inflammatory response syndromes, tetanus, digitalis toxicity, bronchospasms, hypercoagulable states, and as an adjunct to specific anesthetic or analgesic protocols. Further veterinary studies are needed to establish the frequency and importance of magnesium disorders in animals and the potential benefit of magnesium infusions as a therapeutic adjunct to specific diseases. PROGNOSIS: The prognosis for most patients with magnesium disorders is variable and largely dependent on the underlying cause of the disorder.

Hydroxyethyl starch: a review of pharmacokinetics, pharmacodynamics, current products, and potential clinical risks, benefits, and use.

OBJECTIVE: To review and summarize the pharmacokinetics and pharmacodynamics of hydroxyethyl starch (HES), as well as reported risks and benefits of HES infusion, and to provide administration and monitoring recommendations for HES use in dogs and cats. DATA SOURCES: Veterinary and human peer-reviewed medical literature, including scientific reviews, clinical and laboratory research articles, and authors' clinical experience. SUMMARY: HES solutions are the most frequently used synthetic colloid plasma volume expanders in human and veterinary medicine. The majority of research in human medicine has focused on the adverse effects of HES infusion, with emphasis on acute kidney injury and coagulation derangements. The studies often differ in or fail to report factors, such as the type, amount, interval, and concentration of HES administered; the patient population studied; or concurrent fluids administered. Currently, there is no definitive clinical evidence that the reported adverse effects of HES use in human medicine occur in veterinary species. There is little information available on HES administration techniques or simultaneous administration of additional fluids in human and veterinary medicine. The rationale for HES use in small animals has been largely extrapolated from human medical studies and guidelines. A controlled approach to intravenous fluid resuscitation using crystalloid and HES volumes titrated to reach desired resuscitation end point parameters is outlined for small animal practitioners. CONCLUSION: The extrapolation of data from human studies directly to small animals should be done with the knowledge that there may be species variations and different pharmacokinetics with different HES solutions. Veterinary reports indicate that bolus and continuous rate infusions of 6% hetastarch solutions at moderate doses are well tolerated in feline and canine subjects. Further research in domesticated species is necessary to better define and expand the knowledge regarding use of HES solutions in small animal medicine.

More precisely biased: increasing the number of markers is not a silver bullet in genetic bottleneck testing.

In response to our review of the use of genetic bottleneck tests in the conservation literature (Peery et al. 2012,Molecular Ecology, 21, 3403­3418), Hoban et al. (2013, Molecular Ecology, in press) conducted population genetic simulations to show that the statistical power of genetic bottleneck tests can be increased substantially by sampling large numbers of microsatellite loci, as they suggest is now possible in the age of genomics. While we agree with Hoban and co-workers in principle, sampling large numbers of microsatellite loci can dramatically increase the probability of committing type 1 errors(i.e. detecting a bottleneck in a stable population) when the mutation model is incorrectly assumed. Using conservative values for mutation model parameters can reduce the probability of committing type 1 errors, but doing so can result in significant losses in statistical power. Moreover, we believe that practical limitations associated with developing large numbers of high-quality microsatellite loci continue to constrain sample sizes, a belief supported by a literature review of recent studies using next generation sequencing methods to develop microsatellite libraries. conclusion, we maintain that researchers employing genetic bottleneck tests should proceed with caution and carefully assess both statistical power and type 1 error rates associated with their study design.

Comparison of Hb-200 and 6% hetastarch 450/0.7 during initial fluid resuscitation of 20 dogs with gastric dilatation-volvulus.

OBJECTIVE: To compare the use of polymerized stroma-free bovine hemoglobin (Hb-200) and 6% hetastarch 450/0.7 (HES 450/0.7) in 0.9% saline during fluid resuscitation of dogs with gastric dilatation-volvulus (GDV). DESIGN: Prospective, randomized clinical case series. SETTING: Private specialty and referral clinic. ANIMALS: Twenty client-owned dogs presenting with GDV. INTERVENTIONS: Dogs presenting with GDV and abnormal perfusion parameters first received rapid IV infusion of a buffered isotonic replacement crystalloid (15 mL/kg) and IV opioids. Patients were then randomized to receive either Hb-200 (N = 10) or HES 450/0.7 (N = 10). Balanced isotonic replacement crystalloids (10-20 mL/kg IV) were rapidly infused along with either Hb-200 or HES in 5 mL/kg IV aliquots to meet resuscitation end points. MEASUREMENTS AND MAIN RESULTS: Resuscitation was defined as meeting at least 2 of 3 criteria: (1) capillary refill time 1-2 seconds, pink mucous membrane color, strong femoral pulse quality; (2) heart rate (HR) ≤ 150/min; or (3) indirect arterial systolic blood pressure (SBP) > 90 mm Hg. HR, SBP, packed cell volume, hemoglobin, glucose, venous pH, bicarbonate, base excess, anion gap, and colloid osmotic pressure were compared at hospital entry and within 30 minutes post-resuscitation. Compared to the HES group, the Hb-200 group required significantly less colloid (4.2 versus 18.4 mL/kg) and crystalloid (31.3 versus 48.1 mL/kg) to reach resuscitation end points (P = 0.001). Time to resuscitation was significantly shorter in the Hb-200 group (12.5 versus 52.5 min). CONCLUSIONS: Dogs with GDV receiving Hb-200 during initial resuscitation required smaller volumes of both crystalloid and colloid fluids and reached resuscitation end points faster than dogs receiving HES 450/0.7 (P = 0.02).

Reliability of genetic bottleneck tests for detecting recent population declines.

The identification of population bottlenecks is critical in conservation because populations that have experienced significant reductions in abundance are subject to a variety of genetic and demographic processes that can hasten extinction. Genetic bottleneck tests constitute an appealing and popular approach for determining if a population decline has occurred because they only require sampling at a single point in time, yet reflect demographic history over multiple generations. However, a review of the published literature indicates that, as typically applied, microsatellite-based bottleneck tests often do not detect bottlenecks in vertebrate populations known to have experienced declines. This observation was supported by simulations that revealed that bottleneck tests can have limited statistical power to detect bottlenecks largely as a result of limited sample sizes typically used in published studies. Moreover, commonly assumed values for mutation model parameters do not appear to encompass variation in microsatellite evolution observed in vertebrates and, on average, the proportion of multi-step mutations is underestimated by a factor of approximately two. As a result, bottleneck tests can have a higher probability of 'detecting' bottlenecks in stable populations than expected based on the nominal significance level. We provide recommendations that could add rigor to inferences drawn from future bottleneck tests and highlight new directions for the characterization of demographic history.

The role of aquaporin 4 in the brain.

Emerging evidence suggests that aquaporin (AQP) 4 water channels play an important role in water homeostasis in the brain. These water channels are most abundant in the cell membrane of astrocytes, but are also present within ependymal cell membranes and in osmosensory areas of the hypothalamus. Water transport through AQP4 depends on concentration gradients across the membrane, but the rate of transport is determined by the capacity of astrocytes to up- and down-regulate AQP4 numbers, their location within the membrane, and the overall permeability of the channel. Other functions of brain AQP4 involve potassium uptake and release by astrocytes, migration of glial cells, glial scarring, and astrocyte-to-astrocyte cell communication. AQP water channels are involved in formation and control of edema in the brain and in multiple disease processes in the brain, such as seizures and tumors. There is abundant scientific literature on AQP4 describing its structure, function, location, and role in water homeostasis and edema in the brain. Investigation of AQP expression in the canine and feline brain should be pursued so that clinically relevant comparisons between findings in mice, rats, and people and animal patients can be made.

Community partners as co-teachers in resident continuity clinics.

Standard approaches to teaching the management of psychosocial issues in pediatrics--visits to community-based organizations and stand-alone block rotations in developmental-behavioral pediatrics and community pediatrics--neither expose residents to models of interdisciplinary collaboration between faculty preceptors and community providers nor take advantage of the efficacy of learning in continuity clinics. The authors describe their project, developed from an existing Community Pediatrics Training Initiative with long-standing relationships with a domestic violence shelter, a community center for Latino families, and a special needs resource organization for parents. They lay out in detail the project's innovative use of partners from community-based organizations, colocated within pediatric continuity clinics, who teach both residents and faculty about community resources and linkages with multidisciplinary providers. The authors present lessons learned by faculty preceptors, residents, the community partners, and project staff that can guide future applications of this model in other residency training programs. Faculty and residents indicated an increased awareness of available community resources and how linkages can be incorporated into pediatric outpatient visits. Community partners identified keys to successful co-teaching, including readiness to adopt an assertive communication style and frequent presence in the clinics. Project staff recognized the challenges of staff turnover at community-based organizations and the need to choose community partners with expertise that fits the sociodemographic issues of the clinic's patients.