New World

Writing immediately after September 11, 2001, the author reflects on how America's optimism was transformed to a "Bleak New World" and Forests are the largest terrestrial biomass pool, with over half of this biomass stored in the highly productive tropical lowland forests. The future evolution of forest biomass depends critically on the response of tree longevity and growth rates to future climate. We present an analysis of the variation in tree longevity and growth rate using tree-ring data of 3,343 populations and 438 tree species and assess how climate controls growth and tree longevity across world biomes. Tropical trees grow, on average, two times faster compared to trees from temperate and boreal biomes and live significantly shorter, on average (186 ± 138 y compared to 322 ± 201 y outside the tropics). At the global scale, growth rates and longevity covary strongly with temperature. Within the warm tropical lowlands, where broadleaf species dominate the vegetation, we find consistent decreases in tree longevity with increasing aridity, as well as a pronounced reduction in longevity above mean annual temperatures of 25.4 °C. These independent effects of temperature and water availability on tree longevity in the tropics are consistent with theoretical predictions of increases in evaporative demands at the leaf level under a warmer and drier climate and could explain observed increases in tree mortality in tropical forests, including the Amazon, and shifts in forest composition in western Africa. Our results suggest that conditions supporting only lower tree longevity in the tropical lowlands are likely to expand under future drier and especially warmer climates.

Critical Reviews in Oncology/Hematology

Volume 152, August 2020, 103008

A BRAF new world

Author links open overlay panelDanieleFrisonea1AlfredoAddeob

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https://doi.org/10.1016/j.critrevonc.2020.103008Get rights and content

Abstract

BRAF is a rare targetable mutation in non-small-cell lung cancer (NSCLC). Emerging evidence underlines that, rather than a single point mutation, BRAF genes present with a wide array of mutations, essentially in lung adenocarcinoma.

Different BRAF mutations have divergent clinical and therapeutic implications, with a particular distinction between V600E and non-V600E mutations. The latter are at least as frequent in NSCLC as V600E, but lack any proven targeted therapy.

In this paper, we briefly review the current literature and provide an update of scientific knowledge about different types of BRAF mutations in NSCLC.

Sarcocystis.

New World camelids are susceptible to infection by Sarcocystis aucheniae.32–35 This is a different species, although it is biologically similar to the sarcocysts of camels or domestic ruminants. The life cycle appears to depend on a canine definitive host, which becomes infected by eating unprocessed camelid meat containing infective macrocysts. Camelids become infected by eating or drinking in areas contaminated by dog feces containing infectious sporocysts. Other carnivorous hosts have not been identified. Infected camelids develop cysts in striated muscle and cardiac Purkinje fibers. Because unprocessed camelid meat is rarely fed to dogs in North America and elsewhere, new infection is rare here.

Ingestion of large numbers of sporocysts may lead to fulminant, rapidly fatal disease 3 to 4 weeks after exposure.35 Clinical signs include anorexia, weight loss, salivation, weakness, incoordination, fever, recumbency, pale mucous membranes, and diarrhea. Hemorrhagic diathesis and enteritis are common postmortem findings. With lower levels of exposure, disease signs are chronic and may appear years after ingestion. Signs seen include weight loss, muscle stiffness, weakness, abortion, and death.32,35 Diagnosis of infection may be made by performing a muscle biopsy, which would reveal the cysts, areas of necrosis, and eosinophilic myositis. Treatment has not been common. Sulfa antibiotics may be of some value but must be given parenterally to camelids with relatively mature forestomach development.

Biosecurity

George M. Barrington, in Llama and Alpaca Care, 2014

Environmental Risk Factors

New World camelids were domesticated while residing in areas with low population density and wide-open grazing in the mountains of South America. This environment lessened the risk of pathogen exposure and disease propagation, since direct contact between animals was minimized and pathogens were frequently exposed to unfavorable environmental conditions (freezing or thawing and desiccation). Today, camelids commonly reside in environments varying from pasture settings with low population density to dry lots with barns or enclosures with high population density. Specific risk factors include housing (e.g., barns, pastures); physical environment (e.g., bedding, animal exposure, cleaning and disinfection); general hygiene; miscellaneous stresses such as transportation and handling, and atmospheric conditions (e.g., temperature, humidity, ventilation). Fortunately, many of the risk factors associated with environmental conditions can be controlled with implementation of specific biosecurity measures.

Although it is not possible to alter general atmospheric conditions, management changes that provide shelter and improve comfort can be implemented. In cold environments, camelids should have adequate bedding and shelter from excessive moisture and wind. Adequate access to diets with sufficient energy and protein content should be provided during extreme hot and cold conditions. To maintain appropriate hydration, camelids should have free access to clean fresh water sources that do not freeze.

In hot and humid environments such as those found in the southeastern and western United States, heat stress is prevalent. Prevention of heat stress should involve management practices that facilitate a camelid's ability to cool itself.19 Shearing practices should be adjusted to coincide with seasons of high environmental temperature. Camelids should always have access to sufficient shade and be housed with damp, sandy soils, which facilitate thermoregulation. Sprinkling systems that spray the camelids' ventrum and wading ponds may be effective. In severe conditions, air-conditioned stalls may be necessary. Importantly, any time animals are housed in confined areas (either during hot or cold weather), attention must be paid to adequate ventilation. As a general rule, if individuals inspecting a facility are not reasonably comfortable because of excessive heat, cold, wind, moisture, humidity, odors, and so on, it is likely that animals will be similarly uncomfortable.

Frequent manure removal and provision of well-drained soils or bedding material will aide in minimizing pathogen buildup. Feeding practices should be centered on preventing fecal contamination and include the use of hay feeders, hay nets, and raised mangers. Water systems should also be designed to prevent fecal contamination as well as contamination by pests, rodents, or other domestic or wild animals.

Handling, holding, and transportation facilities should be designed and managed to alleviate undue tension or distress. Appropriate ventilation, temperature, and footing should be considered. When appropriate, animals should have access to fresh water and feed during these periods.

Feeding and Nutrition

OWCs and NWCs have no unique nutrient requirements. They may be maintained on a diet of good-quality grass hay or mixed grass and legume hay. Supplemental feeding with concentrates is usually not necessary except for growing juveniles, working animals, and lactating females. Vitamin and mineral supplements are appropriate for specific regions. Numerous feeding regimens are used worldwide, indicative of the adaptability of these animals to available feed. Camelids consume approximately 1% to 2% of their body weight in dry matter when consuming good-quality forage. A maintenance diet should contain 10% to 14% crude protein and 50% to 55% total digestible nutrients (TDNs). During late gestation or heavy lactation, females should consume 60% to 65% TDNs.5

Camelids that eat only native pasture plants may experience fluctuation of body weight. During the dry season animals may lose weight that in other domestic animals could be fatal. NWCs have a feast or famine cycle. With the abundance of grass and shrubs available in the rainy season, an NWC will gain significant weight by storing adipose tissue in muscles and retroperitoneal tissue in the abdomen. During the dry season, NWCs alter their metabolism to use up the stored fat. Management of NWCs maintained in zoos or kept as livestock in non-native countries may not have this normal cycle and may become obese with constant access to feed.

It is important to monitor body weight periodically or perform a body condition evaluation in managed herds. Body condition is assessed by feeling the muscles over the withers and over the ribs. The accumulation of fat between both the forelimbs and hindlimbs should also be taken into consideration. The scoring is performed on the basis of either a 5-point or 10-point system. Low numbers indicate poor condition, medium-range numbers are considered normal, and high numbers indicate overconditioning or obesity.

Sinusitis

Nonfungal sinusitis in New World camelids usually occurs secondary to a maxillary tooth root abscess. Oestrus ovis infestation is another possibility. The airway is affected by discharge from the primary lesion and by remodeling of bone that encroaches on the airway. Characteristically, mucopurulent nasal discharge is unilateral, and nasal air flow is reduced on the affected side. Distortion of facial symmetry and draining tracts on the side of the face may develop. Other findings are reviewed in the section on tooth root abscesses. Radiography is the best way to diagnose the disorder and confirm the infected tooth. Removal of the infected tooth and establishment of drainage usually lead to resolution of the sinus lesions.

Risk Factors

Animal Factors

Sheep, cattle, goats, New World camelids, and kangaroos are affected. Experimental production of the disease in Saanen goats requires two to four times the sheep dose, and feral goats need four to eight times the sheep dose.

Plant Factors

The environmental factors, which encourage the growth of the fungus and the production of sporidesmin, include the type of plants in the pasture and the climatic conditions. Pithomycotoxicosis is commonly associated with ryegrass pastures, but the causative fungus is capable of growing on all kinds of dead leaf material, including cereal hay, and causing facial eczema. In South Africa the ingestion of P. chartarum is thought to enhance the toxicity of Tribulus terrestris.

Pithomycotoxicosis occurs extensively only when pasture is short and contains abundant dead, recently killed plant material, and during warm (grass minimum temperature >12°C), humid weather, which favors growth of the fungus. This is most likely to be a problem in autumn when the summer has been hot and dry, the pasture well eaten back, and good rains fall when the ground is still warm. In such circumstances the grass and the fungus grow rapidly. It is predicted that the disease will increase in range in New Zealand with global warming (Fig. 9-3).

Rabies

Rabies, a lyssavirus, may infect all mammals. Ruminants and New World camelids display a variety of clinical signs, including depression, anorexia, nystagmus, muscle tremors, lameness, ataxia, and posterior paresis. These animals rarely exhibit the aggressive forms of rabies and the disease will usually progress as an ascending paralysis. Fortunately, New World camelids are not able to spit when suffering from rabies.8 Diagnosis is via direct fluorescent antibody testing on the brain of a suspect case. Rabies always needs to be included on a rule-out list in an animal with neurologic signs. Transmission to people is via a bite or saliva from infected animals that gets into an open wound.16 All animals demonstrating neurologic signs should immediately be removed from animal contact areas.

Parenteral Nutrition

Parenteral nutrition is used to provide adequate nutrition intravenously, as long as necessary, when feeding by the gastrointestinal tract is impractical, inadequate, or impossible. The term parenteral nutrition is preferred to total parenteral nutrition because the complete nutritional requirements of large animals are either not completely known or not addressed by intravenous fluid administration. It should be recognized that enteral nutrition represents state-of-the-art medicine because enteral nutrition supports the repair, maintenance, and growth of the gastrointestinal tract to a much greater extent than parenteral nutrition. It should also be recognized that parenteral nutrition should only be contemplated after at least 5 days of inappetence.

The technique is used to supply the nutrient requirements, most importantly protein, of the animal until it returns to normal. In calves affected with persistent diarrhea caused by chronic disease of the alimentary tract, or that cannot or will not eat, total intravenous feeding may be indicated. High concentrations of glucose, protein hydrolysates, lipid emulsions, and electrolytes are given by continuous slow intravenous infusion over a period of several days. Some encouraging results in calves have been published, but the cost-effectiveness of the technique has not been examined.

Parenteral nutrition is an acceptable method of maintaining nutrition in the healthy horse over a period of 10 days. Body weight was maintained at 94% of initial values without clinical evidence of dehydration. No problems were encountered with the long-term intravenous catheterization. The total daily amounts given are calculated on the basis of daily caloric requirement. The intravenous catheter must be inserted down into the cranial vena cava, in which a large volume of blood will dilute the hypertonic concentration of the solution. The potential problems associated with parenteral nutrition include difficulty in the maintenance of a steady intravenous drip, hypertonicity of the solutions used, venous thrombosis, excessive diuresis, catheter sepsis, and bacterial contamination of the solutions.

Parenteral nutrition in foals usually starts with a parenteral daily initial digestible energy of 50 to 55 kcal/kg BW that is designed to address resting energy requirements; the daily energy intake is increased gradually up to a daily target of 120 kcal/kg using a combination of parenteral and enteral nutrition.47 Because of the cost of components, energy density, and availability of products, there are two philosophical approaches to parenteral nutrition in foals: (1) intravenous dextrose and lipid emulsion with 30% to 40% of the caloric intake provided by lipids or (2) intravenous dextrose, amino acids in a nonelectrolyte solution, and lipid emulsion. The latter formulation has been used for parenteral nutrition in alpacas.48 B-complex vitamins are usually added to the final parenteral nutrition solution, and there is no clear consensus on the need for concurrent insulin administration. Typical commercially available products administered in North America are designed for use in humans in a critical care setting and include 50% dextrose solution, an 8.5% amino acid solution without electrolytes, and a 20% lipid emulsion solution, with the lipid solution as the most expensive component. In a retrospective study of 53 foals that received parenteral nutrition including lipids, 32% developed hypertriglyceridemia (>200 mg/dL), and this development was significantly associated with nonsurvival.47 This finding suggests that parenteral nutrition in foals should use limited amounts of lipid for energy, and current recommendations in septic human patients are to provide no more than 5% of the caloric intake from lipid emulsions. Fifteen percent of the 53 foals developed catheter-related complications such as thrombophlebitis or sepsis.47 This emphasizes the need for strict aseptic technique whenever attaching or flushing fluid administration lines and catheters in animals receiving parenteral nutrition.

A practical and effective parenteral nutrition solution for sheep, goats, and New World camelids contains the following components and is administered at a rate of 5% of BW per day:43,44

•

5 L of a commercial balance electrolyte solution (such as lactated Ringer's solution)

•

1 L of 8.5% amino acids (commercially available)

•

500 mL of 50% dextrose

•

20 mL of B-complex vitamins

•

Potassium chloride (20–40 mEq/L) and calcium gluconate 23% (20–50 mL/L) as indicated

The components should be mixed aseptically in this order. Administration is best performed using a centrally located catheter and strict attention should be given to aseptic technique. Hyperglycemia is a common finding in neonatal animals undergoing parenteral nutrition, and the occurrence of hyperglycemia (glucose >180 mg/dL, equivalent to >10 mmol/L) has been associated with an increased likelihood of nonsurvival.49 The widespread availability of low-cost blood glucose point-of-care units has made it much easier to monitor blood glucose concentration every 1 to 2 hours and adjust the fluid administration rate accordingly.

Parenteral nutrition in adult cattle focuses on the administration of 50% dextrose as a continuous rate infusion as part of the treatment of ketosis and hepatic lipidosis and in the supportive treatment in cows that are inappetent or recumbent or have gastrointestinal or infectious diseases.50 Concentrated (50%) dextrose solutions are administered to keep the infused volume low and minimize plasma volume expansion and diuresis. Cows with hepatic lipidosis or prolonged anorexia sometimes require continuous intravenous infusion of dextrose for several days until they can maintain energy balance. The continuous intravenous infusion of 50% dextrose (0.3 g/kg/h) to healthy lactating dairy cows resulted in hyperglycemia and hyperinsulinemia and a marked reduction in plasma phosphorus concentration. Other effects of intravenous dextrose infusion included decreased plasma potassium concentration, decreased dry matter intake and fecal production, and a transient increase in milk production followed by a sustained decrease. All of these effects were reversed after dextrose infusion was stopped.50 The results suggest a slower rate of glucose administration (0.1–0.2 g/kg/h) is more appropriate in lactating dairy cattle.

New World Camelid Crias

Mortality Rates

Mortality of newborn llamas and alpacas is low compared with other production animal species, which in part because New World camelids (NWCs) are frequently kept as companion animals and receive better attention and more intensive treatment in cases of disease. Preweaning mortality rates for llama and alpaca crias are in the range of 2% to 6%, with the great majority of deaths occurring in the first week of life.21,22

Major Causes

Fetal Disease

Abortion and fetal loss after 100 days of gestation have been estimated to occur in 5% of all pregnancies in NWCs.23 Common noninfectious causes for abortion include stress (e.g., related to transport), nutritional deficiencies, and iatrogenic administration of PGF2α or glucocorticoids. Documented infectious causes for abortion include toxoplasmosis, brucellosis, chlamydiosis, listeriosis, leptospirosis, and neosporosis.23

Parturient Disease

Perinatal mortality of crias is strongly associated with the course of parturition and the age of the dam at birth. Dystocia and assisted birth clearly increase the risk for postnatal morbidity and perinatal and postnatal mortality in NWC crias, as in other species.21

Postnatal Disease

The great majority of preweaning mortality occurs in the first week of life, and hypothermia and starvation were determined to be the most common causes of death. Low birth weight was found to considerably increase the risk of perinatal death, as was young age of the dam. Primiparous dams 2 to 3 years old give birth to lighter calves than do older dams and are considered to produce less colostrum, and of inferior quality, than their multiparous herd mates. Small crias have more difficulties standing and getting sufficient amounts of colostrum and lose more body heat because of greater body surface relative to body mass, and thus they are at increased risk of starving to death or of developing perinatal or postnatal diseases.21 A difficult parturition negatively affects perinatal vitality and thereby considerably increases the risk for postnatal morbidity and mortality.22

Toxic Neuropathies and Neurohepatopathies

Toxic neuropathies appear to be rare in camelids as are hepatoencephalopathies. We could find no reports of lead poisoning in Old or New World camelids, but it is likely that this would lead to similar signs as those seen in ruminants. Renal encephalopathy may occur with severe azotemia, but diagnostic and treatment efforts are usually directed toward improving renal function.

The most widely suspected toxic neuropathy was the outbreak of suspected salinomycin-related feed contamination.14 Affected camelids eating a specific feed developed signs that included dyspnea, ataxia, recumbency, and seizures before dying. Blood evaluation demonstrated increases in muscle enzymes. On postmortem evaluation, heart and brain tissues appeared to be affected.

Overdosing lidocaine hydrochloride may lead to depression, behavior changes, ataxia, muscle tremors, opisthotonus, blindness, apnea, hypotensive shock, and seizures. The toxic threshold for camelids is not known but is likely to be similar to what is seen in ruminants (<5 mg/kg or <4 mL/kg of 2% solution). Tolazoline reversal of xylazine has also been associated with the development of neurologic signs, including evidence of anxiousness, hyperesthesia, and convulsions. Other possible signs include profuse salivation, diarrhea, gastrointestinal (GI) hypermotility, tachypnea, and hypotension.15 This toxicosis was associated with giving too much tolazoline too quickly and potentially after much of the xylazine had been metabolized. Giving smaller doses gradually is generally considered safe. Intracarotid injection of a variety of agents has also been associated with the acute development of central neurologic signs, including seizures, obtundation, and central blindness.16 For all these acute reactions to pharmaceuticals, general care is the rule: antiseizure medications as needed, cardiopulmonary support, and a low stress environment where self-trauma is unlikely. Some toxicoses are rapidly fatal, but if the animal maintains or regains cognizance within around 4 hours, the prognosis for general recovery is good; some neurologic deficits may remain and be considered permanent.

Animal Risk Factors

Most herbivores efficiently produce vitamin D3 in the skin, and shorn sheep have higher concentrations of vitamin D3 than do unshorn sheep.1 However, New World camelids are particularly susceptible to vitamin D deficiency, likely as a result of their heavy fleece and evolution in the Andes and attendant exposure to high levels of solar radiation. Movement to lower altitudes, higher latitudes, or housing denies them access to the required amount of sunlight.1,5-7 Inherited rickets in Corriedale sheep is caused by excessive vitamin D catabolism as a result of overexpression of the gene for 25-hydroxyvitamin D3-24-hydroxylase, the enzyme responsible for catabolism of vitamin D.8,9 The disease occurs in housed fattening pigs, likely as a result of errors in feed formulation resulting in vitamin D deficiency.4

Foals have lower serum vitamin D concentrations than do adult horses.10