On some statistical and cerebral aspects of the limits of working memory capacity in anthropoid primates, with particular reference to Pan and Homo, and their significance for human evolution.

Some comparative ontogenetic data imply that effective working-memory capacity develops in ways that are independent of brain size in humans. These are interpreted better from neuroscientific considerations about the continuing development of neuronal architecture in adolescents and young adults, than from one about gross brain mass which already is reached in childhood. By contrast, working-memory capacity in Pan never develops beyond that of three- or four-year-old children. The phylogenetic divergence begs the question of whether it is any longer plausible to infer from the fossil record, that over the past two million years, an ostensibly gradual increase in endocranial volumes, assigned to the genus Homo, can be correlated in a scientifically-meaningful manner with the gradual evolution of our effective executive working memory. It is argued that whereas Pan's effective working-memory capacity is relatively similar to that of its storage working-memory, our working memory is relatively larger with deeper executive control.

Imitation fidelity increases with age in boys, but not in girls: An intriguing finding in a cohort of children aged 3 to 6 years.

Imitation that entails faithful reproduction of demonstrated behavior by reenacting a sequence of actions accurately is a fast and efficient way to acquire new skills as well as to conform to social norms. Previous studies reported that both culture and gender might impinge on young children's fidelity of imitation. We analyzed the imitative behavior of 87 children whose ages ranged from 3 to 6 years. An instrumental task was administered that offered partial (opaque apparatus) or total (transparent apparatus) information about causal connection between the demonstrated actions and their effect in achieving a desired reward. Imitative fidelity (imitating the actions that were demonstrated by an adult model yet were unnecessary for achieving the instrumental goal) increased as a function of age in boys, whereas no differences were found in girls. This lack of increase in girls can be ascribed to their displaying higher degrees of imitation fidelity at an earlier age.

Food allergen analysis: A review of current gaps and the potential to fill them by matrix-assisted laser desorption/ionization.

Food allergy remains a public health, business, and regulatory challenge. Risk analysis (RA) and risk management (RM) of food allergens are of great importance and analysis for food allergens is necessary for both. The current workhorse techniques for allergen analysis (enzyme linked immunosorbent assay [ELISA] and real-time polymerase chain reaction) exhibit recognized challenges including variable and antibody specific responses and detection of species DNA rather than allergen protein, respectively. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) enables protein identification, with potential for multiplex analysis and traceability to the System of International units (SI), aiding global measurement standardization. In this review, recent literature has been systematically reviewed to assess progress in LC-MS/MS and define the potential and benefits of matrix-assisted laser desorption/ionization-time-of-flight MS (MALDI-ToF-MS) technology for allergen analysis. MALDI-ToF-MS of initially intact protein is already applied to verify in silico-derived peptide sequences for LC-MS/MS analysis. We describe the origins of MALDI and its future perspectives, including affinity bead-assisted assays coupled to MALDI. Based on the proliferation of reliable and reproducible MALDI-based clinical applications, the technique should emulate the detection capability (sensitivity) of established allergen detection techniques, whilst reducing technical support and having equivalent multiplexing potential to competing techniques, for example, LC-MS/MS and ELISA. Although unlikely to offer inherent SI traceability, MALDI-based allergen analysis will complement existing MS approaches for allergens. Affinity bead-MALDI appears capable of higher throughput at lower cost per sample than almost any existing technique, enabling repeated sub-sampling as a way to reduce representative sampling issues.

To copy or not to copy? That is the question! From chimpanzees to the foundation of human technological culture.

A prerequisite for copying innovative behaviour faithfully is the capacity of observers' brains, regarded as 'hierarchically mechanistic minds', to overcome cognitive 'surprisal' (see 2.), by maximising the evidence for their internal models, through active inference. Unlike modern humans, chimpanzees and other great apes show considerable limitations in their ability, or 'Zone of Bounded Surprisal', to overcome cognitive surprisal induced by innovative or unorthodox behaviour that rarely, therefore, is copied precisely or accurately. Most can copy adequately what is within their phenotypically habitual behavioural repertoire, in which technology plays scant part. Widespread intra- and intergenerational social transmission of complex technological innovations is not a hall-mark of great-ape taxa. 3 Ma, precursors of the genus Homo made stone artefacts, and stone-flaking likely was habitual before 2 Ma. After that time, early Homo erectus has left traces of technological innovations, though faithful copying of these and their intra- and intergenerational social transmission were rare before 1 Ma. This likely owed to a cerebral infrastructure of interconnected neuronal systems more limited than ours. Brains were smaller in size than ours, and cerebral neuronal systems ceased to develop when early Homo erectus attained full adult maturity by the mid-teen years, whereas its development continues until our mid-twenties nowadays. Pleistocene Homo underwent remarkable evolutionary adaptation of neurobiological propensities, and cerebral aspects are discussed that, it is proposed here, plausibly, were fundamental for faithful copying, which underpinned social transmission of technologies, cumulative learning, and culture. Here, observers' responses to an innovation are more important for ensuring its transmission than is an innovator's production of it, because, by themselves, the minimal cognitive prerequisites that are needed for encoding and assimilating innovations are insufficient for practical outcomes to accumulate and spread intra- and intergenerationally.

Losartan metabolite EXP3179 is a unique blood pressure-lowering AT1R antagonist with direct, rapid endothelium-dependent vasoactive properties.

BACKGROUND AND PURPOSE: Losartan is an anti-hypertensive angiotensin II (ANGII) type 1 receptor (AT1R) blocker (ARB) with many unexpected therapeutic properties, even in non-blood pressure (BP)-related diseases. Administered as a prodrug, losartan undergoes serial metabolism into EXP3179, a metabolite alleged to lack AT1R-blocking properties, and EXP3174, the dominant AT1R antagonist. Having observed that losartan can decrease vascular tone in mice with low AT1R expression and inhibit Marfan aortic widening at very high doses, we investigated whether EXP3179 may have unique, AT1R-independent effects on vascular tone and endothelial function. EXPERIMENTAL APPROACH: We compared the AT1R blocking capabilities of EXP3179 and EXP3174 using AT1R-expressing cell lines. Their BP lowering and vasoactive properties were studied in normal, hypertensive and transgenic rodents, and ex vivo wire myography. KEY RESULTS: We observed that both EXP3179 and EXP3174 can fully block (100%) AT1R signaling in vitro and significantly decrease BP in normotensive and spontaneously hypertensive rats. Only EXP3179 prevented PE-induced contraction by up to 65% (p < 0.01) in L-NAME and endothelium removal-sensitive fashion. Use of transgenic mice revealed that these effects involve the eNOS/caveolin-1 axis and the endothelium-dependent hyperpolarization factor (EDHF). CONCLUSION AND IMPLICATIONS: We provide direct structure-activity evidence that EXP3179 is a BP-lowering AT1R blocker with unique endothelial function-enhancing properties not shared with losartan or EXP3174. The major pharmacological effects of losartan in patients are therefore likely more complex than simple blockade of AT1R by EXP3174, which helps rationalize its therapeutic and prophylactic properties, especially at very high doses. Reports relying on EXP3179 as an AT1R-independent losartan analogue may require careful re-evaluation.

On the working memory of humans and great apes: Strikingly similar or remarkably different?

In this article we review publications relevant to addressing widely reported claims in both the academic and popular press that chimpanzees working memory (WM) is comparable to, if not exceeding, that of humans. WM is a complex multidimensional construct with strong parallels in humans to prefrontal cortex and cognitive development. These parallels occur in chimpanzees, but to a lesser degree. We review empirical evidence and conclude that the size of WM in chimpanzees is 2 ± 1 versus Miller's famous 7 ± 2 in humans. Comparable differences occur in experiments on chimpanzees relating to strategic and attentional WM subsystems. Regardless of the domain, chimpanzee WM performance is comparable to that of humans around the age of 4 or 5. Next, we review evidence showing parallels among the evolution of WM capacity in hominins ancestral to Homo sapiens, the phylogenetic evolution of hominins leading to Homo sapiens, and evolution in the complexity of stone tool technology over this time period.

Hyaenas and early humans in the latest Early Pleistocene of South-Western Europe.

Throughout the Pleistocene, early humans and carnivores frequented caves and large rock-shelters, usually generating bone accumulations. The well-preserved late Early Pleistocene sedimentary sequence at Cueva Negra del Estrecho del Río Quípar (CNERQ) has provided substantial evidence concerning the behavioural and adaptive skills of early humans in Western Europe, such as butchery practices, lithic technology or tending fire, whilst also bearing witness to the bone-altering activities of carnivores. Recent fieldwork has allowed the re-examination of the spatial and taphonomical nature of the macrofaunal assemblage from the upper layers of Complex 2. These layers are somewhat different from most of the underlying sequence, in showing quite a high representation of cranial and post-cranial bones of large mammals, including several Megaloceros carthaginiensis antlers. The presence of Crocuta sp. at Cueva Negra represents one of the earliest instances of this genus in Western Eurasia. Identification of several juvenile Crocuta sp. remains alongside coprolites and bones with carnivore damage, indicates sporadical hyaenid denning activity. Furthermore, the presence of bones with percussion and cut-marks near to several hammerstones suggests a clear albeit limited anthropogenic input. We interpret the available taphonomical and spatial evidence from these layers as reflecting a multi-patterned palimpsest, likely representing the non-simultaneous and short-lived co-existence of hyaenas, humans, and other small carnivores in the Cueva Negra palaeolandscape during the final phase of sedimentation preserved at the site.

Evaluating Indoor Air Chemical Diversity, Indoor-to-Outdoor Emissions, and Surface Reservoirs Using High-Resolution Mass Spectrometry.

Detailed offline speciation of gas- and particle-phase organic compounds was conducted using gas/liquid chromatography with traditional and high-resolution mass spectrometers in a hybrid targeted/nontargeted analysis. Observations were focused on an unoccupied home and were compared to two other indoor sites. Observed gas-phase organic compounds span the volatile to semivolatile range, while functionalized organic aerosols extend from intermediate volatility to ultra-low volatility, including a mix of oxygen, nitrogen, and sulfur-containing species. Total gas-phase abundances of hydrocarbon and oxygenated gas-phase complex mixtures were elevated indoors and strongly correlated in the unoccupied home. While gas-phase concentrations of individual compounds generally decreased slightly with greater ventilation, their elevated ratios relative to controlled emissions of tracer species suggest that the dilution of gas-phase concentrations increases off-gassing from surfaces and other indoor reservoirs, with volatility-dependent responses to dynamically changing environmental factors. Indoor-outdoor emissions of gas-phase intermediate-volatility/semivolatile organic hydrocarbons from the unoccupied home averaged 6-11 mg h-1, doubling with ventilation. While the largest single-compound emissions observed were furfural (61-275 mg h-1) and acetic acid, observations spanned a wide range of individual volatile chemical products (e.g., terpenoids, glycol ethers, phthalates, other oxygenates), highlighting the abundance of long-lived reservoirs resulting from prior indoor use or materials, and their gradual transport outdoors.

The evolution and changing ecology of the African hominid oral microbiome.

The oral microbiome plays key roles in human biology, health, and disease, but little is known about the global diversity, variation, or evolution of this microbial community. To better understand the evolution and changing ecology of the human oral microbiome, we analyzed 124 dental biofilm metagenomes from humans, including Neanderthals and Late Pleistocene to present-day modern humans, chimpanzees, and gorillas, as well as New World howler monkeys for comparison. We find that a core microbiome of primarily biofilm structural taxa has been maintained throughout African hominid evolution, and these microbial groups are also shared with howler monkeys, suggesting that they have been important oral members since before the catarrhine-platyrrhine split ca. 40 Mya. However, community structure and individual microbial phylogenies do not closely reflect host relationships, and the dental biofilms of Homo and chimpanzees are distinguished by major taxonomic and functional differences. Reconstructing oral metagenomes from up to 100 thousand years ago, we show that the microbial profiles of both Neanderthals and modern humans are highly similar, sharing functional adaptations in nutrient metabolism. These include an apparent Homo-specific acquisition of salivary amylase-binding capability by oral streptococci, suggesting microbial coadaptation with host diet. We additionally find evidence of shared genetic diversity in the oral bacteria of Neanderthal and Upper Paleolithic modern humans that is not observed in later modern human populations. Differences in the oral microbiomes of African hominids provide insights into human evolution, the ancestral state of the human microbiome, and a temporal framework for understanding microbial health and disease.

An Interprofessional Senior Medical Student Preparation Course: Improvement in Knowledge and Self-Confidence Before Entering Surgical Training.

PURPOSE: Senior medical students are variably prepared to begin surgical training; and a national curriculum was established through the American College of Surgeons to better prepare senior medical students for surgical training. The purpose of our course is to prepare senior medical students to more effectively enter surgical training programs. We recently enhanced our independently developed surgical training preparation course by increasing exposure to surgical anatomy, medical physiology, surgical skills, and point-of-care ultrasound. We evaluated the impact of our interprofessional training course to increase confidence and readiness among senior medical students entering surgical training. METHODS: The course focused on pre- and post-operative patient care, surgical anatomy, human physiology, and bedside ultrasound. Didactic lectures in anatomy, human physiology, and bedside ultrasound were provided prior to all hands-on simulated patient care sessions and mock surgical procedures. To evaluate our interprofessional curriculum, we administered pre- and post-course surveys, pre- and post-course knowledge tests, and a final surgical anatomy laboratory practical examination to 22 senior medical students who were enrolled in the course. All students created a final surgical anatomy presentation. RESULTS: The students demonstrated a 100% pass rate in surgical anatomy. The knowledge test, which included assessment of knowledge on perioperative surgical decision making, human physiology, and bedside ultrasound, demonstrated an average improvement of 10%. Statistically significant improvements in median confidence values were identified in 10 of 32 surveyed categories, including surgical skills (p < 0.05); 84% of student goals for the course were achieved. The medical students' surveys confirmed increased confidence related to the use of point-of-care ultrasound, teamwork experience, and basic surgical skills through small group interactive seminars and surgical simulation exercises. CONCLUSION: Our preparation for surgical training course resulted in high student satisfaction and demonstrated an increased sense of confidence to begin surgical training. The 10% improvement in medical student knowledge, as evaluated by a written examination, and the significant improvement in confidence level self-assessment scores confirms this surgery preparation course for senior medical students successfully achieved the desired goals of the course.

Continuous measurement of reactive oxygen species inside and outside of a residential house during summer.

Reactive oxygen species (ROS) are an important contributor to adverse health effects associated with ambient air pollution. Despite infiltration of ROS from outdoors, and possible indoor sources (eg, combustion), there are limited data available on indoor ROS. In this study, part of the second phase of Air Composition and Reactivity from Outdoor aNd Indoor Mixing campaign (ACRONIM-2), we constructed and deployed an online, continuous, system to measure extracellular gas- and particle-phase ROS during summer in an unoccupied residence in St. Louis, MO, USA. Over a period of one week, we observed that the non-denuded outdoor ROS (representing particle-phase ROS and some gas-phase ROS) concentration ranged from 1 to 4 nmol/m3 (as H2 O2 ). Outdoor concentrations were highest in the afternoon, coincident with peak photochemistry periods. The indoor concentrations of particle-phase ROS were nearly equal to outdoor concentrations, regardless of window-opening status or air exchange rates. The indoor/outdoor ratio of non-denuded ROS (I/OROS ) was significantly less than 1 with windows open and even lower with windows closed. Combined, these observations suggest that gas-phase ROS are efficiently removed by interior building surfaces and that there may be an indoor source of particle-phase ROS.

Authenticity and the Potability of Coconut Water - a Critical Review.

BACKGROUND: The content of the endosperm of the coconut (Cocos nucifera L.) contains "coconut water". This practically sterile liquid which is prized for its delicate, albeit labile, flavor when fresh, has had a recent dramatic increase in global demand. The organoleptic superiority of water from young coconuts means that degree of maturity at harvesting is the most influential factor in yield and composition. OBJECTIVE: To provide a guide to establishing the authenticity and the potability of samples of coconut water. METHOD: Review and evaluate the literature on the factors that determine the composition and stability of coconut water. RESULTS: Data is presented on the variances in natural composition, maturity, processing-induced compositional changes, adulterations, product recalls, classical and instrumental methods of analysis and on the available composition standards of coconut water. CONCLUSIONS: Advice is provided for official food analysts, and others, on prudent approaches as how to ascertain the authenticity and potability, or otherwise, of coconut water samples.

Doctor of Physical Therapy Education in a Hybrid Learning Environment: Reimagining the Possibilities and Navigating a "New Normal".

Professional physical therapist education has experienced a transformation over the last few decades, moving to a doctoring profession with more autonomy and a broader scope of practice. These changes have occurred in parallel with systemic and structural changes in health care and higher education, both of which have experienced challenges with improving access and controlling costs, and have become a centerpiece of legislative and political discourse. At the same time, advances in technology have introduced new possibilities in education, with the emergence of online, blended, and "flipped" learning models that supplement or replace face-to-face instruction with distance learning. Hybrid education is a type of blended learning, utilizing both face-to-face and online instructional strategies. In a hybrid learning environment, online content may be delivered synchronously or asynchronously, replacing traditional face-to-face instructional time and reducing "seat time" for students. Recent attention has been brought to online and hybrid/blended learning in physical therapist education in the wake of the COVID-19 pandemic, as programs have been required to abruptly move from face-to-face to remote instruction. Hybrid and other forms of blended learning strategies have been described at the physical therapist education course level. However, there is no literature describing hybrid learning implementation at the physical therapist education program "levels," and there has been limited discussion on best practices for delivering hybrid, blended, and online instruction in physical therapist education. This perspective provides an overview of hybrid education, describes theoretical frameworks that guide implementation of a hybrid education curriculum, and discusses future directions for hybrid physical therapist education and educational research.

Critical Review of Analytical and Bioanalytical Verification of the Authenticity of Coffee.

BACKGROUND: The driving factors for the commercial adulteration of coffee are reviewed. OBJECTIVE: Methods have been assessed for the identification of the most common materials used to adulterate coffee by dilution, to establish the geographic origins, the genotypes of beans, and to assess the authenticity of Kopi Luwak coffee. METHOD: The literature was surveyed manually and electronically from 1820 to 2018. RESULTS: A flow diagram has been developed to summarize the best approaches to deal with the authentication of coffee. CONCLUSIONS: Encouragement is given to the interlaboratory validation of spectroscopic approaches, the exploration of civet cat deoxyribonucleic acid for the identification of Kopi Luwak, and the development of appropriately large and well-curated datasets of authenticity information across multiple techniques. HIGHLIGHTS: The current analytical difficulties in the authentication of coffee are highlighted and suggestions made to improve the situation.

Identification of a Biomarker Panel for Early Detection of Lung Cancer Patients.

Lung cancer is the most common cause of cancer-related mortality worldwide, characterized by late clinical presentation (49-53% of patients are diagnosed at stage IV) and consequently poor outcomes. One challenge in identifying biomarkers of early disease is the collection of samples from patients prior to symptomatic presentation. We used blood collected during surgical resection of lung tumors in an iTRAQ isobaric tagging experiment to identify proteins effluxing from tumors into pulmonary veins. Forty proteins were identified as having an increased abundance in the vein draining from the tumor compared to "healthy" pulmonary veins. These protein markers were then assessed in a second cohort that utilized the mass spectrometry (MS) technique: Sequential window acquisition of all theoretical fragment ion spectra (SWATH) MS. SWATH-MS was used to measure proteins in serum samples taken from 25 patients <50 months prior to and at lung cancer diagnosis and 25 matched controls. The SWATH-MS analysis alone produced an 11 protein marker panel. A machine learning classification model was generated that could discriminate patient samples from patients within 12 months of lung cancer diagnosis and control samples. The model was evaluated as having a mean AUC of 0.89, with an accuracy of 0.89. This panel was combined with the SWATH-MS data from one of the markers from the first cohort to create a 12 protein panel. The proteome signature developed for lung cancer risk can now be developed on further cohorts.

Origins of the method of standard additions and of the use of an internal standard in quantitative instrumental chemical analyses.

The origin of the method of standard additions (SAM) and of the use of internal standard (IS) in instrumental chemical analysis and their spread into other areas has been reviewed. Recorded applications of IS range from flame spectroscopy in 1877 through multiple techniques to current use in NMR and standard additions with isotopically labelled internal standards in hyphenated techniques. For SAM, applications stemmed from polarography in 1937 and spread to most instrumental methods. Some misconceptions on priorities are corrected.

Molecular charge associated with antiarrhythmic actions in a series of amino-2-cyclohexyl ester derivatives.

A series of amino-2-cyclohexyl ester derivatives were studied for their ion channel blocking and antiarrhythmic actions in the rat and a structure-activity analysis was conducted. The compounds are similar in chemical structure except for ionizable amine groups (pK values 6.1-8.9) and the positional arrangements of aromatic naphthyl moieties. Ventricular arrhythmias were produced in rats by coronary-artery occlusion or electrical stimulation. The electrophysiological effects of these compounds on rat heart sodium channels (Nav1.5) expressed in Xenopus laevis oocytes and transient outward potassium currents (Kv4.3) from isolated rat ventricular myocytes were examined. The compounds reduced the incidence of ischemia-related arrhythmias and increased current threshold for induction of ventricular fibrillo-flutter (VFt) dose-dependently. As pK increased compounds showed a diminished effectiveness against ischemia-induced arrhythmias, and were less selective for ischemia- versus electrically-induced arrhythmias. Where tested, compounds produced a concentration-dependent tonic block of Nav1.5 channels. An increased potency for inhibition of Nav1.5 occurred when the external pH (pHo) was reduced to 6.5. Some compounds inhibited Kv4.3 in a pH-independent manner. Overall, the differences in antiarrhythmic and ion channel blocking properties in this series of compounds can be explained by differences in chemical structure. Antiarrhythmic activity for the amino-2-cyclohexyl ester derivatives is likely a function of mixed ion channel blockade in ischemic myocardium. These studies show that drug inhibition of Nav1.5 occurred at lower concentrations than Kv4.3 and was more sensitive to changes in the ionizable amine groups rather than on positional arrangements of the naphthyl constituents. These results offer insight into antiarrhythmic mechanisms of drug-ion channel interactions.