Identifying Experimental Tool Use Through Confocal Microscopy

Characterizing use-wear traces quantitatively is a valid way to improve the capacity of use-wear analysis. This aim has been on specialists’ agenda since the beginning of the discipline. Micropolish quantification is especially important, as this type of trace allows the identification of worked materials. During the last decade, confocal microscopy has been used as a promising approach to address this question. Following previous efforts in plant microwear characterization (Ibáñez et al. Journal of Archaeological Science, 48, 96–103, 2014; Journal of Archaeological Science, 73, 62–81, 2016), here we test the capacity of the method for correctly grouping experimental tools used for working eight types of materials: bone, antler, wood, fresh hide, dry hide, wild cereals, domestic cereals, and reeds. We demonstrate, for the first time, that quantitative texture analysis of use-wear micropolish based on confocal microscopy can consistently identify tools used for working different contact materials. In this way, we are able to move toward using texture analysis as part of the standard functional analysis of prehistoric instruments.This study is part of the projects HAR2016-74999-P, HAR2015-68566-P, and HAR2016-81971-REDT funded by the Spanish Ministerio de Ciencia, Innovación y Universidades.Peer reviewe

Rethinking use-wear analysis and experimentation as applied to the study of past hominin tool use

In prehistoric human populations, technologies played a fundamental role in the acquisition of different resources and are represented in the main daily living activities, such as with bone, wooden, and stone-tipped spears for hunting, and chipped-stone tools for butchering. Considering that paleoanthropologists and archeologists are focused on the study of different processes involved in the evolution of human behavior, investigating how hominins acted in the past through the study of evidence on archeological artifacts is crucial. Thus, investigat ing tool use is of major importance for a comprehensive understanding of all processes that characterize human choices of raw materials, techniques, and tool types. Many functional assumptions of tool use have been based on tool design and morphology according to archeologists’ interpretations and ethnographic observations. Such assumptions are used as baselines when inferring human behavior and have driven an improvement in the methods and techniques employed in functional studies over the past few decades. Here, while arguing that use-wear analysis is a key discipline to assess past hominin tool use and to interpret the organization and variability of artifact types in the archeological record, we aim to review and discuss the current state-of-the-art methods, protocols, and their limitations. In doing so, our discussion focuses on three main topics: (1) the need for fundamental improvements by adopting established methods and techniques from similar research fields, (2) the need to implement and combine different levels of experimentation, and (3) the crucial need to establish standards and protocols in order to improve data quality, standard ization, repeatability, and reproducibility. By adopting this perspective, we believe that studies will increase the reliability and applicability of use-wear methods on tool function. The need for a holistic approach that combines not only use-wear traces but also tool technology, design, curation, durability, and efficiency is also debated and revised. Such a revision is a crucial step if archeologists want to build major inferences on human decision making behavior and biocultural evolution processes.info:eu-repo/semantics/publishedVersio

First GIS analysis of modern stone tools used by wild chimpanzees (Pan troglodytes verus) in Bossou, Guinea, West Africa

Stone tool use by wild chimpanzees of West Africa offers a unique opportunity to explore the evolutionary roots of technology during human evolution. However, detailed analyses of chimpanzee stone artifacts are still lacking, thus precluding a comparison with the earliest archaeological record. This paper presents the first systematic study of stone tools used by wild chimpanzees to crack open nuts in Bossou (Guinea-Conakry), and applies pioneering analytical techniques to such artifacts. Automatic morphometric GIS classification enabled to create maps of use wear over the stone tools (anvils, hammers, and hammers/anvils), which were blind tested with GIS spatial analysis of damage patterns identified visually. Our analysis shows that chimpanzee stone tool use wear can be systematized and specific damage patterns discerned, allowing to discriminate between active and passive pounders in lithic assemblages. In summary, our results demonstrate the heuristic potential of combined suites of GIS techniques for the analysis of battered artifacts, and have enabled creating a referential framework of analysis in which wild chimpanzee battered tools can for the first time be directly compared to the early archaeological record.Leverhulme Trust [IN-052]; MEXT [20002001, 24000001]; JSPS-U04-PWS; FCT-Portugal [SFRH/BD/36169/2007]; Wenner-Gren Foundation for Anthropological Researc

Structure–activity study of N-((trans)-4-(2-(7-cyano-3,4-dihydroisoquinolin-2(1H)-yl)ethyl)cyclohexyl)-1H-indole-2-carboxamide (SB269652), a bitopic ligand that acts as a negative allosteric modulator of the dopamine D2 receptor

We recently demonstrated that SB269652 (1) engages one protomer of a dopamine D2 receptor (D2R) dimer in a bitopic mode to allosterically inhibit the binding of dopamine at the other protomer. Herein, we investigate structural deter- minants for allostery, focusing on modifications to three moieties within 1. We find that orthosteric “head” groups with small 7-substituents were important to maintain the limited negative cooperativity of analogues of 1, and replacement of the tetrahydroisoquinoline head group with other D2R “privileged structures” generated orthosteric antagonists. Additionally, replacement of the cyclohexylene linker with polymethylene chains conferred linker length dependency in allosteric pharma- cology. We validated the importance of the indolic NH as a hydrogen bond donor moiety for maintaining allostery. Replacement of the indole ring with azaindole conferred a 30-fold increase in affinity while maintaining negative cooperativity. Combined, these results provide novel SAR insight for bitopic ligands that act as negative allosteric modulators of the D2R

A multicentre, randomised controlled trial to compare the clinical and cost-effectiveness of Lee Silverman Voice Treatment versus standard NHS Speech and Language Therapy versus control in Parkinson’s disease: a study protocol for a randomised controlled trial

Abstract: Background: Parkinson’s disease (PD) affects approximately 145,519 people in the UK. Speech impairments are common with a reported prevalence of 68%, which increase physical and mental demands during conversation, reliance on family and/or carers, and the likelihood of social withdrawal reducing quality of life. In the UK, two approaches to Speech and Language Therapy (SLT) intervention are commonly available: National Health Service (NHS) SLT or Lee Silverman Voice Treatment (LSVT LOUD®). NHS SLT is tailored to the individuals’ needs per local practice typically consisting of six to eight weekly sessions; LSVT LOUD® comprises 16 sessions of individual treatment with home-based practice over 4 weeks. The evidence-base for their effectiveness is inconclusive. Methods/design: PD COMM is a phase III, multicentre, three-arm, unblinded, randomised controlled trial. Five hundred and forty-six people with idiopathic PD, reporting speech or voice problems will be enrolled. We will exclude those with a diagnosis of dementia, laryngeal pathology or those who have received SLT for speech problems in the previous 2 years. Following informed consent and completion of baseline assessments, participants will be randomised in a 1:1:1 ratio to no-intervention control, NHS SLT or LSVT LOUD® via a central computer-generated programme, using a minimisation procedure with a random element, to ensure allocation concealment. Participants randomised to the intervention groups will start treatment within 4 (NHS SLT) or 7 (LSVT LOUD®) weeks of randomisation. Primary outcome: Voice Handicap Index (VHI) total score at 3 months. Secondary outcomes include: VHI subscales, Parkinson’s Disease Questionnaire-39; Questionnaire on Acquired Speech Disorders; EuroQol-5D-5 L; ICECAP-O; resource utilisation; adverse events and carer quality of life. Mixed-methods process and health economic evaluations will take place alongside the trial. Assessments will be completed before randomisation and at 3, 6 and 12 months after randomisation. The trial started in December 2015 and will run for 77 months. Recruitment will take place in approximately 42 sites around the UK. Discussion: The trial will test the hypothesis that SLT is effective for the treatment of speech or voice problems in people with PD compared to no SLT. It will further test whether NHS SLT or LSVT LOUD® provide greater benefit and determine the cost-effectiveness of both interventions. Trial registration: International Standard Randomised Controlled Trials Number (ISRCTN) Registry, ID: 12421382. Registered on 18 April 2016

A multicentre, randomised controlled trial to compare the clinical and cost-effectiveness of Lee Silverman Voice Treatment versus standard NHS Speech and Language Therapy versus control in Parkinson’s disease: a study protocol for a randomised controlled trial

Abstract: Background: Parkinson’s disease (PD) affects approximately 145,519 people in the UK. Speech impairments are common with a reported prevalence of 68%, which increase physical and mental demands during conversation, reliance on family and/or carers, and the likelihood of social withdrawal reducing quality of life. In the UK, two approaches to Speech and Language Therapy (SLT) intervention are commonly available: National Health Service (NHS) SLT or Lee Silverman Voice Treatment (LSVT LOUD®). NHS SLT is tailored to the individuals’ needs per local practice typically consisting of six to eight weekly sessions; LSVT LOUD® comprises 16 sessions of individual treatment with home-based practice over 4 weeks. The evidence-base for their effectiveness is inconclusive. Methods/design: PD COMM is a phase III, multicentre, three-arm, unblinded, randomised controlled trial. Five hundred and forty-six people with idiopathic PD, reporting speech or voice problems will be enrolled. We will exclude those with a diagnosis of dementia, laryngeal pathology or those who have received SLT for speech problems in the previous 2 years. Following informed consent and completion of baseline assessments, participants will be randomised in a 1:1:1 ratio to no-intervention control, NHS SLT or LSVT LOUD® via a central computer-generated programme, using a minimisation procedure with a random element, to ensure allocation concealment. Participants randomised to the intervention groups will start treatment within 4 (NHS SLT) or 7 (LSVT LOUD®) weeks of randomisation. Primary outcome: Voice Handicap Index (VHI) total score at 3 months. Secondary outcomes include: VHI subscales, Parkinson’s Disease Questionnaire-39; Questionnaire on Acquired Speech Disorders; EuroQol-5D-5 L; ICECAP-O; resource utilisation; adverse events and carer quality of life. Mixed-methods process and health economic evaluations will take place alongside the trial. Assessments will be completed before randomisation and at 3, 6 and 12 months after randomisation. The trial started in December 2015 and will run for 77 months. Recruitment will take place in approximately 42 sites around the UK. Discussion: The trial will test the hypothesis that SLT is effective for the treatment of speech or voice problems in people with PD compared to no SLT. It will further test whether NHS SLT or LSVT LOUD® provide greater benefit and determine the cost-effectiveness of both interventions. Trial registration: International Standard Randomised Controlled Trials Number (ISRCTN) Registry, ID: 12421382. Registered on 18 April 2016

Hydrogen bonding control in the oxidative cyclisation of 1,5-dienes

The regioselective dihydroxylation of a series of functionalised polyenes is described. Under acidic conditions, the osmate ester derivatives obtained from oxidation with OsO4/TMEDA undergo an intramolecular cyclisation reaction forming functionalised tetrahydrofurans with high stereoselectivity and in good yield. The generality of this method is illustrated with an application to the synthesis of a bis-tetrahydrofuran ring system. © 2001 Elsevier Science Ltd