A new large pantherine and a sabre-toothed cat (Mammalia, Carnivora, Felidae) from the late Miocene hominoid-bearing Khorat sand pits, Nakhon Ratchasima Province, northeastern Thailand.

We describe two large predators from the hominoid-bearing Khorat sand pits, Nakhon Ratchasima Province, northeastern Thailand: a new genus of pantherine, Pachypanthera n. gen., represented by partial mandible and maxilla and an indeterminate sabre-toothed cat, represented by a fragment of upper canine. The morphological characters of Pachypanthera n. gen., notably the large and powerful canine, the great robustness of the mandibular body, the very deep fossa for the m. masseter, the zigzag HSB enamel pattern, indicate bone-cracking capacities. The genus is unique among Felidae as it has one of the most powerful and robust mandibles ever found. Moreover, it may be the oldest known pantherine, as other Asian pantherines are dated back to the early Pliocene. The taxa we report here are the only carnivorans known from the late Miocene of Thailand. Although the material is rather scarce, it brings new insights to the evolutionary history of Neogene mammals of Southeast Asia, in a geographic place which is partly "terra incognita."

Amphipithecine primates are stem anthropoids: cranial and postcranial evidence.

Since their discovery in 1927, the phylogenetic status of the Myanmar amphipithecines has been highly debated. These fossil primates are recognized either as anthropoids or as adapiform strepsirrhines. This uncertainty was largely the consequence of a limited fossil record consisting mostly of jaw fragments but lacking the critical cranial elements that might resolve this debate. We report here cranial remains associated with an ulna from a single individual pertaining to the amphipithecine Ganlea megacanina. In addition to anthropoid-like dentognathic characters, Ganlea displays several ulna and skull features that testify to its anthropoid affinities (e.g. short subvertically oriented lacrimal duct, lacrimal foramen and bone inside the orbit, maxillary contribution to the lower orbital rim, fused metopic suture). By contrast to crown anthropoids, however, Ganlea lacks postorbital closure, confirming that postorbital closure appeared later than many anthropoid dentognathic characters and evolved convergently in extant tarsiers and anthropoids. Thus, amphipithecines must now be recognized as stem anthropoids offering a unique window on the early evolution of cranial and skeletal features in anthropoids, and reinforcing the hypothesis of an origin and early diversification of anthropoids in Asia.

Asian monsoons in a late Eocene greenhouse world.

The strong present-day Asian monsoons are thought to have originated between 25 and 22 million years (Myr) ago, driven by Tibetan-Himalayan uplift. However, the existence of older Asian monsoons and their response to enhanced greenhouse conditions such as those in the Eocene period (55-34 Myr ago) are unknown because of the paucity of well-dated records. Here we show late Eocene climate records revealing marked monsoon-like patterns in rainfall and wind south and north of the Tibetan-Himalayan orogen. This is indicated by low oxygen isotope values with strong seasonality in gastropod shells and mammal teeth from Myanmar, and by aeolian dust deposition in northwest China. Our climate simulations support modern-like Eocene monsoonal rainfall and show that a reinforced hydrological cycle responding to enhanced greenhouse conditions counterbalanced the negative effect of lower Tibetan relief on precipitation. These strong monsoons later weakened with the global shift to icehouse conditions 34 Myr ago.

Psychometric evaluation of ADAS-Cog and NTB for measuring drug response.

AIMS: To conduct a psychometric analysis to determine the adequacy of instruments that measure cognition in Alzheimer's disease trials. BACKGROUND: Both the Alzheimer's Disease Assessment Scale - Cognition (ADAS-Cog) and the Neuropsychological Test Battery (NTB) are validated outcome measures for clinical trials in Alzheimer's disease and are approved also for regulatory purposes. However, it is not clear how comparable they are in measuring cognitive function. In fact, many recent trials in Alzheimer's disease patients have failed and it has been questioned if ADAS-Cog still is a sensitive measure. MATERIALS AND METHODS: The present paper examines the psychometric properties of ADAS-Cog and NTB, based on a post hoc analysis of data from a clinical trial (NCT01024660), which was conducted by AstraZeneca, in mild-to-moderate Alzheimer's disease (AD) patients, with a Mini Mental State Examination (MMSE) Total score 16-24. Acceptability, reliability, different types of validity and ability to detect change were assessed using relevant statistical methods. Total scores of both tests, as well as separate domains of both tests, including the Wechsler Memory Scale (WMS), Rey Auditory Verbal Learning Test (RAVLT) and Delis-Kaplan Executive Function System (D-KEFS) Verbal Fluency Condition, were analyzed. RESULTS: Overall, NTB performed well, with acceptable reliability and ability to detect change, while ADAS-Cog had insufficient psychometric properties, including ceiling effects in 8 out of a total of 11 ADAS-Cog items in mild AD patients, as well as low test-retest reliability in some of the items. DISCUSSION: Based on a direct comparison on the same patient sample, we see advantages of the NTB compared with the ADAS-Cog for the evaluation of cognitive function in the population of mild-to-moderate AD patients. The results suggest that not all of ADAS-Cog items are relevant for both mild and moderate AD population. CONCLUSIONS: This validation study demonstrates satisfactory psychometric properties of the NTB, while ADAS-Cog was found to be psychometrically inadequate.

Satisfactory long-term MRI after autologous chondrocyte implantation at the knee.

PURPOSE: Autologous chondrocyte implantation (ACI) to address isolated condylar lesions is supposed to limit degenerative deterioration in neutrally aligned knees. Here, we report long-term results of the first-generation ACI technique with periosteal flap. METHODS: Twelve patients, 29 years old on average, were included on the basis of pre-operative MRI selection of lesions >2 cm2. Cartilage carrots were harvested arthroscopically, then cultured and finally re-implanted within a mean time interval of 12 weeks. Ten-year MRI results were analysed according to a semi-quantitative scale, along with functional assessment based on International Knee Documentation Committee score, Lysholm et al. score and the Tegner et al. activity scale. RESULTS: One patient secondarily required valgus tibial osteotomy with mosaic plasty. Another incurred graft hypertrophy that necessitated arthroscopic peeling. MRI showed that cartilage repair filled more than 50% of the initial defect in 9 patients. Standard radiographs revealed slight narrowing of the joint line. Overall, functional scores improved durably by 50%, although activity level decreased substantially. CONCLUSION: ACI contained degenerative changes within moderate stages while maintaining durable functional improvement. However, in the absence of controls, it was difficult to differentiate between these findings and the spontaneous evolution of non-treated lesions. LEVEL OF EVIDENCE: Case series, Level IV.

Longitudinal Cognitive Decline in Patients With Mild Cognitive Impairment or Dementia Due to Alzheimer's Disease.

Sensitive cognitive assessments accurately detect and track cognitive decline in Alzheimer's disease. The Cogstate battery was used to measure cognitive change in cognitively normal participants and in individuals with mild cognitive impairment and mild Alzheimer's disease enrolled in the Australian Imaging, Biomarker and Lifestyle Rate of Change Substudy. Over 18 months, verbal episodic memory performance declined for mild cognitive impairment and mild Alzeheimer's disease groups when compared to cognitively normal participants. Frequent assessments of episodic memory may facilitate early detection of cognitive decline due to Alzheimer's disease.

Evolutionary ecology of Miocene hominoid primates in Southeast Asia.

The evolutionary history and palaeoecology of orangutans remains poorly understood until today. The restricted geographic distribution of extant Pongo indicates specific ecological needs. However, it is not clear whether these needs were shared by the great diversity of fossil pongines known from the Miocene to the Pleistocene. Here we show how niche modelling of stable carbon and oxygen isotope data of the carbonate fraction of dental enamel can be used to reconstruct the paleoecology of fossil and modern pongines and associated mammal communities. We focus on Khoratpithecus ayeyarwadyensis, a Late Miocene pongine from Myanmar and the sister clade to extant orangutans, and compare it to its associated mammal fauna and other fossil and extant pongines. The results are consistent with a vertical position high up in the canopy of a forested habitat with purely C3 vegetation for K. ayeyarwadyensis as well as the contemporaneous Sivapithecus. Although their positions in the modelled isotopic niche space look similar to the ecological niche occupied by modern Pongo, a comparison of the modelled niches within the pongine clade revealed possible differences in the use of microhabitats by the Miocene apes.

Battlefield Medicine: Anesthesia and Critical Care in the Combat Zone.

The US Military Joint Trauma System has been developed to mitigate the harsh conditions under which medical providers care for combat casualties and provide continuity of care from the battlefield to US medical centers. We review the components of this system with emphasis on combat trauma care under fire and the role of the anesthesiologist and intensivist in this continuum of care. An important link in the chain of survival is the Air Force Critical Care Aeromedical Transport Team, which provides critical care while transporting casualties from the theater to higher levels of care outside the war zone and home.

A new primate from the Middle Eocene of Myanmar and the Asian early origin of anthropoids.

A new genus and species of anthropoid primate, Bahinia pondaungensis gen. et sp. nov., is described from the Yashe Kyitchaung locality in the Late Middle Eocene Pondaung Formation (Myanmar). It is related to Eosimias, but it is represented by more complete remains, including upper dentition with associated lower jaw fragment. It is interpreted as a new representative of the family Eosimiidae, which corresponds to the sister group of the Amphipithecidae and of all other anthropoids. Eosimiidae are now recorded from three distinct Middle Eocene localities in Asia, giving support to the hypothesis of an Asian origin of anthropoids.

A fossil lemur from the Oligocene of Pakistan.

In the absence of a comprehensive fossil record, the origin and early evolution of Malagasy lemurs have been subject to much uncertainty. We report here the discovery of a strepsirrhine fossil with strong cheirogaleid lemur affinities, Bugtilemur mathesoni gen. et sp. nov., from early Oligocene deposits of the Bugti Hills (Balochistan, Pakistan). Bugtilemur represents the earliest record of Lemuriformes, which hence appear to have already diversified outside of Madagascar at least 30 million years ago. This fossil clearly enhances the critical role of the Indian subcontinent in the early diversification of lemurs and constrains paleobiogeographic models of strepsirrhine lemur evolution.

Toxicant-disease-environment interactions associated with suppression of immune system, growth, and reproduction.

The effects of marginal malnourishment , infections, and environmental chemicals on growth and reproductive success in Swiss-Webster white mice and wild deer mice were studied with fractional factorial designs. Interaction effects were discovered. For example, malnourished mice were more sensitive to virus exposure and environmental chemicals (a plant growth regulator or polychlorinated biphenyls). Since several commercial plant growth regulators also appear to suppress the immune system, these results cast doubt on the adequacy of current toxicity testing procedures in which factors are studied individually and not in combination.

Serum and plasma metabolites associated with postpartum ovulation and pregnancy risks in suckled beef cows subjected to artificial insemination.

Two experiments were conducted to determine relationships of blood metabolite concentrations, BW, BCS, and rump fat depth with postpartum ovulation and pregnancy risks, as well as their utility in predicting those outcomes in suckled beef cows. In experiment 1, plasma glucose collected 10 and 3 d before AI of suckled beef cows at seven locations did not differ between cows that had resumed estrous cycles (ovulated) before AI compared with anovulatory cows, whereas plasma glucose 3 d before AI was greater (P < 0.01) in cows that became pregnant compared with nonpregnant cows. Serum beta-hydroxybutyrate (BHB) tended (P = 0.09) to be less in ovulatory cows compared with anovulatory cows 10 d before AI, but was unrelated to pregnancy status. Receiver-operator derived true-positive (sensitivity) and false-positive (1-specificity) risks were determined for plasma glucose and serum BHB as predictors for postpartum ovulation and pregnancy status. Serum BHB 3 d before AI produced true-positive and false-positive risks of 82% and 37%, respectively, when predicting ovulatory status before AI. Serum BHB 10 d before AI produced a true-positive and false-positive risks of 92% and 25%, respectively, when predicting pregnancy status. In experiment 2, blood was collected weekly for 12 wk from multiparous suckled beef cows to assess blood metabolite concentrations in addition to concurrent weekly assessments of BW, BCS, and rump fat. When blood metabolites and physical measures were normalized to parturition reflecting changes occurring during the first 6 wk after calving, we observed reduced (P < 0.05) concentrations of serum BHB and NEFA, and greater (P < 0.05) rump fat and BCS in cows that ovulated before first AI, whereas reduced (P < 0.05) plasma glucose was characteristic of cows that became pregnant. When blood metabolites and physical measures were normalized to the onset of the AI program reflecting changes during 6 wk before AI, ovulatory cows had increased (P < 0.05) BCS and lower (P < 0.05) NEFA from 3 to 6 wk before the onset of the AI program compared with anovulatory cows. With all predictor variables in regression models, some multiple correlation coefficients (R2) exceeded 50% when predicting postpartum ovulatory status, but those for predicting pregnancy risk were less than 25%. Although measures of BCS and BHB during 6 wk after calving were related to postpartum ovulation risk, rump fat, glucose, BCS, and NEFA were associated with cows that were ovulatory and pregnant.

Influence of heat and humidity on the airway obstruction induced by exercise in asthma.

We examined the degree of airway obstruction that developed in eight asthmatics who exercised while breathing air under four conditions: (a) ambient room temperature and water content; (b) body temperature and ambient water content; (c) ambient room temperature fully saturated; and (d) body temperature fully saturated. These test conditions were performed in random order. Multiple aspects of pulmonary mechanics were measured before and 5 min after exercise. When air at ambient conditions was inhaled, the expected airway obstruction developed after exercise, and all variables changes significantly from their pre-challenge values. Heating the air to body temperature did not influence this response. Increasing the humidity at ambient temperatures significantly blunted the response, and by inhaling body temperature, fully saturated air completely prevented it from occurring. Thus, the water content of inspired air is an important variable in the development of exercise induced asthma.

Two split-time artificial insemination programs in suckled beef cows.

Our objective was to determine which of 2 split-time AI programs applied to suckled beef cows would result in greater pregnancy risk. Suckled beef cows (n = 1,062) at 12 locations in 4 states (CO, KS, MY, and WA) were enrolled. Cows were treated on d -7 with a progesterone insert concurrent with 100 µg GnRH and on d 0 with 25 mg PGF plus removal of the insert. Estrus-detection patches were affixed to cows at insert removal. The study was designed as a completely randomized experiment of 2 treatment combinations. Within location and balanced for parity (primiparous vs. multiparous), cows were assigned randomly to 2 treatment times (55 vs. 65 h after CIDR insert removal) at which time estrus-detection patches were assessed. Estrus was defined to have occurred when an estrus-detection patch was > 50% colored (activated). Cows determined to be in estrus were inseminated at either 55 or 65 h, whereas the residual nonestrous cows in both treatment times received GnRH at 55 or 65 h but were inseminated 20 h later at 75 or 85 h, respectively. Pregnancy outcomes were determined at 36 d after AI and at the end of the breeding season. Thus, pregnancy outcomes of interest were compared between the 55 + 75-h treatment combination and that of the 65+85-h combination. Expression of estrus was greater ( = 0.001) by 65 h after PGF than by 55 h (62.0% vs. 41.9%), respectively, and this proportion was influenced by parity (time x parity interaction; = 0.006). As a result, proportionally more ( < 0.001) cows received the timed AI at 75 than 85 h (59.4% vs. 40.6%). Similar proportions of cows not in estrus by 55 or 65 h were detected in estrus by 75 or 85 h (40.1% vs. 39.3%), respectively. The cumulative proportion of cows in estrus by 75 h was less ( < 0.001) than that by 85 h (66.7% vs. 76.7%), respectively. Pregnancy risks at 36 d differed among treatments, with cows detected in estrus and inseminated at 55 or 65 h having greater pregnancy risks than their time-inseminated herd mates at 75 or 85 h (62.3% vs.49.7%), respectively. Overall pregnancy risk for cows in the 65+85-h treatment combination was greater at 36 d than for cows in the 55 + 75-h treatment combination (61.0% vs. 51.4%), respectively. We conclude that the 65 + 85-h treatment combination produced more pregnancies than the 55 + 75-h combination, but its implementation may be somewhat less convenient in terms of cow handling times.

The Occurrence of PVYO, PVYN, and PVYN:O Strains of Potato virus Y in Certified Potato Seed Lot Trials in Washington and Oregon.

Totals of 960 and 286 certified potato seed lots from locations across North America were planted in trials in Washington and Oregon, respectively, in 2001 to 2003 and tested for strains of Potato virus Y (PVY). The incidence of PVYO-infected lots averaged 16.4 and 25.9% in the Washington and Oregon trials, respectively. There was a general trend of increasing incidence of the PVYO, PVYN:O, and PVYN strains during this period, as evidenced by more infected cultivars, sites of seed origin, and number of seed growers providing infected seed lots. In particular, there was a dramatic increase in seed lots with the PVYN:O strain from 2002 to 2003. PVYN:O, in contrast to PVYO, which only causes yield reduction, also causes internal and external damage to tubers, making them unmarketable. In 2003, PVYN:O occurred in seed lots originating in eight states and three Canadian provinces. The increased incidence of PVYN:O was likely due to the difficulty in differentiating this strain from PVYO. The prevalence of PVY in potato seed lots documented herein poses a threat to potato production in the United States and suggests that current measures to reduce the incidence of this virus are inadequate.

A double-sided fabrication process for intrafascicular parylene C based electrode arrays.

After the development of a single-sided fabrication process for intrafascicular parylene C based electrode arrays tests showed that an increase in integration density can only be achieved by a double-side process. The process uses 25 µm thick platinum iridium foil, which is thinned down with the laser and sandwiched between two 10 µm thick parylene C layers. Utilizing a picosecond laser (355 nm Nd:YVO4) it was possible to fabricate 40 µm thick electrodes that can be implanted directly in the nerve without relying on additional support layers like chitosan or silk. The fabricated samples feature three 80 µm diameter electrodes on each side and a large ground electrode that is opened to both sides. Impedance mismatches from front to back side as a result of the fabrication process are compensated by electrochemical deposition of nanostructured platinum. This step makes it possible to bring the impedances of the small electrodes down to the range of just a few kΩ at 1 kHz and illustrate the additionally gained surface due to the picosecond laser ablation on the front side electrodes. The safely injectable charge per pulse was found to be 635.75 µC/cm2 for such coated electrodes. Optical investigations show that this fabrication process offers an alternative to established lithographic processes for thin and flexible electrode arrays in neural implants.