Earliest known hominin activity in the Philippines by 709 thousand years ago.

Over 60 years ago, stone tools and remains of megafauna were discovered on the Southeast Asian islands of Flores, Sulawesi and Luzon, and a Middle Pleistocene colonization by Homo erectus was initially proposed to have occurred on these islands1-4. However, until the discovery of Homo floresiensis in 2003, claims of the presence of archaic hominins on Wallacean islands were hypothetical owing to the absence of in situ fossils and/or stone artefacts that were excavated from well-documented stratigraphic contexts, or because secure numerical dating methods of these sites were lacking. As a consequence, these claims were generally treated with scepticism 5 . Here we describe the results of recent excavations at Kalinga in the Cagayan Valley of northern Luzon in the Philippines that have yielded 57 stone tools associated with an almost-complete disarticulated skeleton of Rhinoceros philippinensis, which shows clear signs of butchery, together with other fossil fauna remains attributed to stegodon, Philippine brown deer, freshwater turtle and monitor lizard. All finds originate from a clay-rich bone bed that was dated to between 777 and 631 thousand years ago using electron-spin resonance methods that were applied to tooth enamel and fluvial quartz. This evidence pushes back the proven period of colonization 6 of the Philippines by hundreds of thousands of years, and furthermore suggests that early overseas dispersal in Island South East Asia by premodern hominins took place several times during the Early and Middle Pleistocene stages1-4. The Philippines therefore may have had a central role in southward movements into Wallacea, not only of Pleistocene megafauna 7 , but also of archaic hominins.

Fluticasone in mild to moderate atopic dermatitis relapse: A randomized controlled trial.

BACKGROUND: The long-term efficacy of corticosteroids to prevent atopic dermatitis (AD) relapses has partially been addressed in children. This study compared an intermittent dosing regimen of fluticasone propionate (FP) cream 0.05% with its vehicle base in reducing the risk of relapse in children with stabilized AD. METHODS: A randomized controlled, multicentric, double-blind trial was conducted. Children (2-10 years) with mild/moderate AD (exclusion criteria: >30% affected body surface area and/or head) were enrolled into an Open-label Stabilization Phase (OSP) of up to 2 weeks on twice daily FP. Those who achieved treatment success entered the Double-blind Maintenance Phase (DMP). They were randomly allocated to receive FP or vehicle twice-weekly on consecutive days for 16 weeks. The primary study endpoint was relapse rate; time to relapse and severity of disease were also studied. Kaplan-Meier estimates were calculated. RESULTS: Fifty-four patients (29 girls) entered the OSP (23 mild AD) and 49 (26 girls) continued into the DMP. Mean age was 5.5 (SD: 2.8) and 5.1 (SD: 2.3) yrs for FP and vehicle groups, respectively. Four patients withdrew from the DMP (two in every group). Patients treated with FP twice weekly had a 2.7 fold lower risk of experiencing a relapse than patients treated with vehicle (relative risk 2.72, SD: 1.28; p=0.034). FP was also superior to vehicle for delaying time to relapse. Both treatment therapies were well tolerated. CONCLUSION: This long-term study shows that twice weekly FP provides an effective maintenance treatment to control the risk of relapse in children with AD.

Mothers and offspring: The rabbit as a model system in the study of mammalian maternal behavior and sibling interactions.

UNLABELLED: This article is part of a Special Issue "Parental Care". Jay Rosenblatt effectively promoted research on rabbit maternal behavior through his interaction with colleagues in Mexico. Here we review the activities of pregnant and lactating rabbits (Oryctolagus cuniculus), their neuro-hormonal regulation, and the synchronization of behavior between mother and kits. Changing concentrations of estradiol, progesterone, and prolactin throughout gestation regulate nest-building (digging, straw-carrying, fur-pulling) and prime the mother's brain to respond to the newborn. Nursing is the only mother-young contact throughout lactation. It happens once/day, inside the nest, with ca. 24h periodicity, and lasts around 3min. Periodicity and duration of nursing depend on a threshold of suckling as procedures reducing the amount of nipple stimulation interfere with the temporal aspects of nursing, though not with the doe's maternal motivation. Synchronization between mother and kits, critical for nursing, relies on: a) the production of pheromonal cues which guide the young to the mother's nipples for suckling; b) an endogenous circadian rhythm of anticipatory activity in the young, present since birth. Milk intake entrains the kits' locomotor behavior, corticosterone secretion, and the activity of several brain structures. Sibling interactions within the huddle, largely determined by body mass at birth, are important for: a) maintaining body temperature; b) ensuring normal neuromotor and social development. Suckling maintains nursing behavior past the period of abundant milk production but abrupt and efficient weaning occurs in concurrently pregnant-lactating does by unknown factors. CONCLUSION: female rabbits have evolved a reproductive strategy largely dissociating maternal care from maternal presence, whose multifactorial regulation warrants future investigations.

Empirical monotherapy with meropenem or combination therapy: the microbiological point of view.

The increase in the number of clinical isolates of multiresistant Enterobacteriaceae and Pseudomonas aeruginosa raises problems in decision-making on empirical treatments for severe Gram-negative bacilli-associated infections. The aim of our study is to determine the resistance of meropenem in our setting and the co-resistance of a combination of this compound with two antibiotics from different families: amikacin and ciprofloxacin. Between 2009 and 2013, a total of 81,310 clinical isolates belonging to the main species of Enterobacteriaceae and 39,191 clinical isolates of P. aeruginosa isolated in 28 hospitals in the Valencian Community on the South East Mediterranean Coast of Spain were analyzed using data provided by RedMiva (microbiological surveillance network of the Valencian Community). Meropenem resistance in Enterobacteriaceae increased from 0.16 % in 2009 to 1.25 % in 2013. Very few Enterobacteriaceae strains resistant to meropenem were sensitive to ciprofloxacin; in contrast, the combination of meropenem and amikacin led to a marked decrease in the risk of the microorganisms being resistant to both drugs (RR = 34 in 2013). In the case of P. aeruginosa, meropenem resistance also increased (from 14.32 % in 2009 to 24.52 % in 2013). Most meropenem-resistant P. aeruginosa isolates were also resistant to fluoroquinolones. However, the addition of amikacin led to a more than three-fold decrease in the risk of resistance. In our setting, empirical treatment with meropenem is adequate in enterobacterial infections, but poses difficulties when infection due to P. aeruginosa is suspected, in which case a combination of meropenem and amikacin has been shown to have a higher microbiological success rate.

Serum, milk, and tissue monensin concentrations in cattle with adequate and potentially toxic dietary levels of monensin: pharmacokinetics and diagnostic interpretation.

Used in both beef cattle and dairy cows, monensin can provide many health benefits but can, when unintended overexposures occur, result in adverse effects. Information on serum and tissue concentrations following overexposure and/or overt toxicosis which may aid in diagnostics and clinical outcome is lacking. The aim of this study was to determine concentrations of monensin in biological specimens following oral exposure for 10 days to an approved dose (1 mg/kg) and a higher dose (5 mg/kg) of monensin given daily on a body weight basis to 10 dairy cows. No deaths were reported; cows receiving 5 mg/kg showed early signs of toxicosis including depression, decreased feed intake, and diarrhea after 4 days of exposure. Histopathological findings were minimal in most cows. Pharmacokinetic modeling of the detected serum concentrations for the 1 and 5 mg/kg dose groups determined the Cmax , Tmax, and t1/2λ to be 0.87 and 1.68 ng/mL, 2.0 and 1.0 h, and 1.76 and 2.32 days, respectively. Mixed regression models showed that the dose level and days since last dose were significantly associated with monensin concentrations in all four tissues, and with cardiac troponin levels. The high dose resulted in a significant elevation of monensin in tissues at approximately 4.7 times compared to the monensin concentrations in the tissues of animals from the low-dose group. The cTnI concentrations in the high-dose group were 2.1 times that of cTnI in the low-dose group. Thus, the ability to diagnose monensin overexposure and/or toxicosis will improve from knowledge of biological monensin concentrations from this study.

Towards a standardized initial training program in experimental microsurgery for pediatric surgeons. / Hacia un programa inicial de formación estandarizadoen microcirugía experimental para cirujanos pediátricos.

OBJECTIVE: To describe a basic training program in microsurgery and to analyze the learning curve through the process, including improvement in operating times and functional outcome. MATERIALS AND METHODS: Our learning program included basic, transitional, and experimental models. The experimental model included tail vein cannulation, intestinal resection and anastomosis, dissection, division and anastomosis of the cava and aorta. Wistar rats (66.7% male; 406.9 ± 38.9 grams) were used. The program adhered to the 3R principle and obtained animal welfare committee approval. RESULTS: Mean tail vein cannulation time was 2.4 ± 1.2 minutes. Mean intestinal resection and jejunocolic anastomosis time was 14.8 ± 2.7 minutes and 10.4 ± 3 minutes, respectively. All anastomoses were functionally valid. Mean vessel dissection time was 22.9 ± 7.7 minutes, aortic artery anastomosis was 17.2 ± 7.1 minutes, and vena cava anastomosis was 25.9 ± 7.3 minutes. 66.7% of vena cava anastomoses were functionally valid vs. 88.9% for the aorta. The time required for all procedures decreased after the third attempt, except for vena cava anastomoses, which remained similar in all 9 procedures. CONCLUSIONS: Our model demonstrated that the procedures were suitable for trainer progression in terms of surgical time and functional outcome. Microsurgical training would benefit from standardized programs to optimize results.

OBJETIVO: Describimos un programa de formación básica en microcirugía y analizamos la curva de aprendizaje a través del proceso, incluyendo la mejora en los tiempos operatorios y en el resultado funcional del procedimiento. MATERIAL Y METODOS: Nuestro programa de aprendizaje incluye modelos básicos, de transición y experimentales. Dentro del modelo experimental se incluyeron: canulación de la vena de la cola, resección y anastomosis intestinal, disección, sección y anastomosis de la cava y la aorta. Se emplearon ratas Wistar (66,7% machos; 406,9 ± 38,9 gramos), el programa se adhirió al principio de las 3R y obtuvo la aprobación del comité de bienestar animal. RESULTADOS: El tiempo medio de canulación de la vena de la cola fue de 2.4 ± 1,2 minutos. El tiempo medio de resección intestinal y anastomosis yeyunocólica de 14.8 ± 2,7 minutos y 10.4 ± 3 minutos, respectivamente. Todas las anastomosis fueron funcionalmente válidas. El tiempo medio de la disección de vasos fue de 22,9 ± 7,7 minutos, la anastomosis de la arteria aorta de 17,2 ± 7,1 minutos, mientras que la anastomosis de la vena cava fue de 25,9 ± 7,3 minutos. El 66,7% de las anastomosis de la vena cava fueron funcionalmente válidas en comparación con el 88,9% de la aorta. El tiempo requerido para todos los procedimientos disminuyó después del tercer intento, excepto para las anastomosis de vena cava, que se mantuvo similar en los 9 procedimientos. CONCLUSIONES: Nuestro modelo demostró que los procedimientos eran adecuados para la progresión del entrenador en términos de tiempo quirúrgico y resultado funcional. La formación microquirúrgica se beneficiaría de programas estandarizados para optimizar los resultados.

[Sepsis Code: dodging mortality in a tertiary hospital]. / Código Sepsis: esquivando la mortalidad en un hospital terciario.

OBJECTIVE: In the hospital of La Princesa, the "Sepsis Code" (CSP) began in 2015, as a multidisciplinary group that provides health personnel with clinical, analytical and organizational tools, with the aim of the detection and early treatment of patients with sepsis. The objective of this study is to evaluate the impact of CSP implantation on mortality and to determine the variables associated with an increase in it. METHODS: A retrospective analytical study of patients with CSP alert activation from 2015 to 2018 was conducted. Clinical-epidemiological variables, analytical parameters, and severity factors such as admission to critical care units (UCC) and the need for amines were collected. Statistical significance was established at p < 0.05. RESULTS: We included 1,121 patients. The length of stay was 16 days and 32% required admission to UCC. Mortality showed a statistically significant linear downward trend from 24% in 2015 to 15% in 2018. The predictive mortality variables with statistically significant association were lactate > 2 mmol/L, creatinine > 1.6 mg/dL and the need for amines.>5.0%, mortality at the time of chart review 62.0%, and 6-months-post-discharge readmission 47.7%. CONCLUSIONS: The implementation of Sepsis Code decreases the mortality of patients with sepsis and septic shock. The presence of a lactate > 2 mmol/L, creatinine > 1.6 mg/dL and/or the need to administer amines in the first 24 hours, are associated with an increase in mortality in the patient with sepsis.

Pre-clinical validation of a turbine-based ventilator for invasive ventilation-The ACUTE-19 ventilator.

BACKGROUND: The Severe Acute Respiratory Syndrome (SARS)-Coronavirus 2 (CoV-2) pandemic pressure on healthcare systems can exhaust ventilator resources, especially where resources are restricted. Our objective was a rapid preclinical evaluation of a newly developed turbine-based ventilator, named the ACUTE-19, for invasive ventilation. METHODS: Validation consisted of (a) testing tidal volume (VT) delivery in 11 simulated models, with various resistances and compliances; (b) comparison with a commercial ventilator (VIVO-50) adapting the United Kingdom Medicines and Healthcare products Regulatory Agency-recommendations for rapidly manufactured ventilators; and (c) in vivo testing in a sheep before and after inducing acute respiratory distress syndrome (ARDS) by saline lavage. RESULTS: Differences in VT in the simulated models were marginally different (largest difference 33ml [95%-confidence interval (CI) 31-36]; P<.001ml). Plateau pressure (Pplat) was not different (-0.3cmH2O [95%-CI -0.9 to 0.3]; P=.409), and positive end-expiratory pressure (PEEP) was marginally different (0.3 cmH2O [95%-CI 0.2 to 0.3]; P<.001) between the ACUTE-19 and the commercial ventilator. Bland-Altman analyses showed good agreement (mean bias, -0.29, [limits of agreement, 0.82 to -1.42], and mean bias 0.56 [limits of agreement, 1.94 to -0.81], at a Pplat of 15 and 30cmH2O, respectively). The ACUTE-19 achieved optimal oxygenation and ventilation before and after ARDS induction. CONCLUSIONS: The ACUTE-19 performed accurately in simulated and animal models yielding a comparable performance with a VIVO-50 commercial device. The acute 19 can provide the basis for the development of a future affordable commercial ventilator.

[Pre-clinical validation of a turbine-based ventilator for invasive ventilation-The ACUTE-19 ventilator]. / Validación preclínica de un respirador de turbina para la ventilación invasiva: el respirador ACUTE-19.

Background: The severe acute respiratory syndrome-coronavirus 2 pandemic pressure on healthcare systems can exhaust ventilator resources, especially where resources are restricted. Our objective was a rapid preclinical evaluation of a newly developed turbine-based ventilator, named the ACUTE-19, for invasive ventilation. Methods: Validation consisted of (a) testing tidal volume delivery in 11 simulated models, with various resistances and compliances; (b) comparison with a commercial ventilator (VIVO-50) adapting the United Kingdom Medicines and Healthcare products Regulatory Agency-recommendations for rapidly manufactured ventilators; and (c) in vivo testing in a sheep before and after inducing acute respiratory distress syndrome by saline lavage. Results: Differences in tidal volume in the simulated models were marginally different (largest difference 33 ml [95% CI 31 to 36]; P < .001). Plateau pressure was not different (-0.3 cmH2O [95% CI -0.9 to 0.3]; P = .409), and positive end-expiratory pressure was marginally different (0.3 cmH2O [95% CI 0.2 to 0.3]; P < .001) between the ACUTE-19 and the commercial ventilator. Bland-Altman analyses showed good agreement (mean bias -0.29 [limits of agreement 0.82 to -1.42], and mean bias 0.56 [limits of agreement 1.94 to -0.81], at a plateau pressure of 15 and 30 cmH2O, respectively). The ACUTE-19 achieved optimal oxygenation and ventilation before and after acute respiratory distress syndrome induction. Conclusions: The ACUTE-19 performed accurately in simulated and animal models yielding a comparable performance with a VIVO-50 commercial device. The ACUTE-19 can provide the basis for the development of a future affordable commercial ventilator.

Abdominal cystic lymphangiomas in pediatrics: surgical approach and outcomes.

BACKGROUND: Abdominal Cystic lymphangiomas (ACL) are uncommon benign masses usually presented during infancy. Although extremely rare, they may cause complications; therefore, the recommended therapy is surgical excision. The purpose of this study is to report our experience with the diagnosis and surgical treatment of ACL in pediatric population. MATERIAL AND METHODS: From January 1994 to December 2009, 10 patients (6 females; 4 males) with diagnostic confirmation of ACL were retrospectively included in study. Children's age ranged between 9 months and 8 years (mean age at diagnosis was 2.5 years). Clinical presentation, cyst location, imaging studies employed, surgical approach and pathologic features were analyzed. RESULTS: The most common symptom was abdominal pain but three cases were incidentally detected. One case had presented with acute abdomen after traumatic haemorrhage of the tumor. All patients were diagnosed with ultrasonography as first-line radiological study. MRI was used in last three cases. At surgery, concomitant bowel resection was necessary in 3 children. Location of the lesion (omentum, mesentery) did not influence the outcome but surgery was more difficult (operative time over three hours) in patients with lymphangioma affecting mesentery of the jejunum. Mean hospital stay after surgery was 6.7 days. Mean follow-up was 5.1 years. No recurrence of the cystic lymphangioma was noticed during follow-up. One case developed an intestinal occlusion due to bowel adhesions 1 year after surgery. CONCLUSIONS: ACL usually affect infants and young children and may present with spectrum of symptoms from an incidental finding to an acute life-threatening abdominal obstruction. Complete excision of the tumor is a safe and effective method in the management of ACL in pediatric population. Surgery is mandatory to avoid potential complications.

Description of ovine model for testing ventilator prototypes in the COVID-19 pandemic.

The COVID-19 pandemic has revealed a ventilator deficit in the global health system for this scenario. For this reason, several national and international projects have been developed to get done prototypes of ventilators which could be easy and fast to manufacture. One of the requirements of the AEMPS for conducting clinical studies with new prototypes is through the validation of these new prototypes in an animal model. Therefore, it is important to achieve an animal model which allows us to easily reproduce different clinical scenarios. In this article, we describe the use of a sheep as a research model to assess a prototype ventilator. The animal was anesthetized for 10 h in which the prototype was tested in up to 6 different scenarios. This model is effective and easy to reproduce, making it an excellent choice for this kind of research.

Quantitative and qualitative analysis of semantic verbal fluency in patients with temporal lobe epilepsy. / Análisis cuantitativo y cualitativo de la fluidez verbal semántica en pacientes con epilepsia del lóbulo temporal.

INTRODUCTION: Patients with temporal lobe epilepsy (TLE) perform poorly on semantic verbal fluency (SVF) tasks. Completing these tasks successfully involves multiple cognitive processes simultaneously. Therefore, quantitative analysis of SVF (number of correct words in one minute), conducted in most studies, has been found to be insufficient to identify cognitive dysfunction underlying SVF difficulties in TLE. OBJECTIVES: To determine whether a sample of patients with TLE had SVF difficulties compared with a control group (CG), and to identify the cognitive components associated with SVF difficulties using quantitative and qualitative analysis. METHODS: SVF was evaluated in 25 patients with TLE and 24 healthy controls; the semantic verbal fluency test included 5 semantic categories: animals, fruits, occupations, countries, and verbs. All 5 categories were analysed quantitatively (number of correct words per minute and interval of execution: 0-15, 16-30, 31-45, and 46-60seconds); the categories animals and fruits were also analysed qualitatively (clusters, cluster size, switches, perseverations, and intrusions). RESULTS: Patients generated fewer words for all categories and intervals and fewer clusters and switches for animals and fruits than the CG (P<.01). Differences between groups were not significant in terms of cluster size and number of intrusions and perseverations (P>.05). CONCLUSIONS: Our results suggest an association between SVF difficulties in TLE and difficulty activating semantic networks, impaired strategic search, and poor cognitive flexibility. Attention, inhibition, and working memory are preserved in these patients.

Iodine-129 for determining the origin of salinity in groundwater in Pampanga, Philippines.

Assessing groundwater vulnerability from salinity contamination is vital and relevant to meet the increasing demand for freshwater. Iodine-129 (129I, half-life = 15.7 million years), a radioisotope of iodine, was used as an environmental tracer for the possible origin of salinization in groundwater (e.g., natural rock weathering, evaporated water, seawater, brine fossil water, contamination). In July 2017 (wet season), thirty-two (32) water samples were taken from production wells of different localities in Pampanga, a province in the Philippines that relies heavily on groundwater for freshwater sources. Hydrogeochemical (mainly Cl) and stable water isotopes (δ2H and δ18O) were able to identify seven samples potentially affected by seawater intrusion. The salinity origin of these samples was investigated using iodine-129 and iodine-127 isotopes by generating two graphs: 129I vs. chloride and 129I/127I ratio vs. 1/127I. 129I vs. Cl graph was capable of showing a clear distinction between different salinity origins. Five out of the seven samples were being affected by evaporated water, one sample from possible wastewater, and one sample from brine fossil water. A conceptual model was produced to summarize the results. Compiled end-members (e.g., natural brine, seawater, modern rain) were plotted in the 129I/127I ratio vs. 1/127I graph to show the interaction between two recharge sources. The results of this study will be helpful to the government, civil society, and other organizations for monitoring, policymaking, and management of the groundwater and the subsurface formations that will be crucial to continuously supply the freshwater needs of the present and future generation.

Taphonomy and chronosequence of the 709 ka Kalinga site formation (Luzon Island, Philippines).

The recently described site of Kalinga in the Philippines adds to our understanding of Early-Middle Pleistocene hominin behaviour. Yet, disentangling the natural from the anthropogenic modifications that have taken place in such an old archaeological site is challenging. In this paper we use a set of taphonomic tools at hand to rectify the distortion made by natural processes during the formation of the Kalinga site. From the description of the ribs completeness, surface damages and scattering in the excavation, one can reconstruct the butchery, transport and deposition sequence of the rhino carcass and its post-depositional disturbances and diagenetic evolution of the site. We conclude that the rhino and the stone artefacts potentially used to deflesh the carcass were transported by a mudflow from its butchery place over a few meters only and got stuck and mixed with an older faunal assemblage that was transported by a small stream.

Description of ovine model for testing ventilator prototypes in the COVID-19 pandemic. / Descripción de un modelo ovino para la prueba de ventiladores de urgencia en la pandemia de COVID-19.

The COVID-19 pandemic has revealed a ventilator deficit in the global health system for this scenario. For this reason, several national and international projects have been developed to get done prototypes of ventilators which could be easy and fast to manufacture. One of the requirements of the AEMPS for conducting clinical studies with new prototypes is through the validation of these new prototypes in an animal model. Therefore, it is important to achieve an animal model which allows us to easily reproduce different clinical scenarios. In this article, we describe the use of a sheep as a research model to assess a prototype ventilator. The animal was anesthetized for 10hours in which the prototype was tested in up to 6different scenarios. This model is effective and easy to reproduce, making it an excellent choice for this kind of research.

Initial clinical outcomes and prognostic variables in the implementation of a Code Sepsis in a high complexity University Hospital.

OBJECTIVE: To assess the impact of the first months of application of a Code Sepsis in a high complexity hospital, analyzing patient´s epidemiological and clinical characteristics and prognostic factors. METHODS: A long-term observational study was carried out throughout a consecutive period of seven months (February 2015 - September 2015). The relationship with mortality of risk factors, and analytic values was analyzed using uni- and multivariate analyses. RESULTS: A total of 237 patients were included. The in-hospital mortality was 24% at 30 days and 27% at 60 days. The mortality of patients admitted to Critical Care Units was 30%. Significant differences were found between the patients who died and those who survived in mean levels of creatinine (2.30 vs 1.46 mg/dL, p <0.05), lactic acid (6.10 vs 2.62 mmol/L, p <0.05) and procalcitonin (23.27 vs 12.73 mg/dL, p<0.05). A statistically significant linear trend was found between SOFA scale rating and mortality (p<0.05). In the multivariate analysis additional independent risk factors associated with death were identified: age > 65 years (OR 5.33, p <0.05), lactic acid > 3 mmol/L (OR 5,85, p <0,05), creatinine > 1,2 mgr /dL (OR 4,54, p <0,05) and shock (OR 6,57, P <0,05). CONCLUSIONS: The epidemiological, clinical and mortality characteristics of the patients in our series are similar to the best published in the literature. The study has identified several markers that could be useful at a local level to estimate risk of death in septic patients. Studies like this one are necessary to make improvements in the Code Sepsis programs.