Sedimentation, re-sedimentation and chronologies in archaeologically-important caves: problems and prospects

Excavations in the photic zones of caves have provided cornerstone archaeological sequences in many parts of the world. Before the appearance of modern dating techniques, cave deposits provided clear evidence for the antiquity, relative ages and co-occurrence of ancient human remains, material culture and fauna. Earlier generations of archaeologists had generally rather limited understanding of taphonomic and depositional processes, but the twentieth century saw considerable improvement in excavation and analytical techniques. The advent of modern dating and chronological methodologies offers very powerful tools for the analysis of cave fill deposits and this has resulted in the recognition of chronological incoherence in parts of some sites, with consequent re-evaluation of previous archaeological disputes. Obtaining multiple dates per context provides a means to assess the integrity and coherence of the archaeological and environmental records from cave fills. In the case of the Haua Fteah (Libya), this technique allowed the recognition of chronological coherence in low-energy depositional environments and limited recycling in high-energy contexts. We provide a conceptual model of the relationship between recycling, sedimentation rate and process energy. High-resolution investigation enables recognition of the complexity of the formation of cave sequences, thus an increasingly sophisticated understanding of human behaviour and environmental relationships in the past, and potentially gives a new life to old data

Sedimentation, re-sedimentation and chronologies in archaeologically-important caves: problems and prospects

Excavations in the photic zones of caves have provided cornerstone archaeological sequences in many parts of the world. Before the appearance of modern dating techniques, cave deposits provided clear evidence for the antiquity, relative ages and co-occurrence of ancient human remains, material culture and fauna. Earlier generations of archaeologists had generally rather limited understanding of taphonomic and depositional processes, but the twentieth century saw considerable improvement in excavation and analytical techniques. The advent of modern dating and chronological methodologies offers very powerful tools for the analysis of cave fill deposits and this has resulted in the recognition of chronological incoherence in parts of some sites, with consequent re-evaluation of previous archaeological disputes. Obtaining multiple dates per context provides a means to assess the integrity and coherence of the archaeological and environmental records from cave fills. In the case of the Haua Fteah (Libya), this technique allowed the recognition of chronological coherence in low-energy depositional environments and limited recycling in high-energy contexts. We provide a conceptual model of the relationship between recycling, sedimentation rate and process energy. High-resolution investigation enables recognition of the complexity of the formation of cave sequences, thus an increasingly sophisticated understanding of human behaviour and environmental relationships in the past, and potentially gives a new life to old data

Monitoring Cognitive and Emotional Processes Through Pupil and Cardiac Response During Dynamic Versus Logical Task

The paper deals with the links between physiological measurements and cognitive and emotional functioning. As long as the operator is a key agent in charge of complex systems, the definition of metrics able to predict his performance is a great challenge. The measurement of the physiological state is a very promising way but a very acute comprehension is required; in particular few studies compare autonomous nervous system reactivity according to specific cognitive processes during task performance and task related psychological stress is often ignored. We compared physiological parameters recorded on 24 healthy subjects facing two neuropsychological tasks: a dynamic task that require problem solving in a world that continually evolves over time and a logical task representative of cognitive processes performed by operators facing everyday problem solving. Results showed that the mean pupil diameter change was higher during the dynamic task; conversely, the heart rate was more elevated during the logical task. Finally, the systolic blood pressure seemed to be strongly sensitive to psychological stress. A better taking into account of the precise influence of a given cognitive activity and both workload and related task-induced psychological stress during task performance is a promising way to better monitor operators in complex working situations to detect mental overload or pejorative stress factor of error

Anti-prion drug mPPIg5 inhibits PrP(C) conversion to PrP(Sc).

Prion diseases, also known as transmissible spongiform encephalopathies, are a group of fatal neurodegenerative diseases that include scrapie in sheep, bovine spongiform encephalopathy (BSE) in cattle and Creutzfeldt-Jakob disease (CJD) in humans. The 'protein only hypothesis' advocates that PrP(Sc), an abnormal isoform of the cellular protein PrP(C), is the main and possibly sole component of prion infectious agents. Currently, no effective therapy exists for these diseases at the symptomatic phase for either humans or animals, though a number of compounds have demonstrated the ability to eliminate PrPSc in cell culture models. Of particular interest are synthetic polymers known as dendrimers which possess the unique ability to eliminate PrP(Sc) in both an intracellular and in vitro setting. The efficacy and mode of action of the novel anti-prion dendrimer mPPIg5 was investigated through the creation of a number of innovative bio-assays based upon the scrapie cell assay. These assays were used to demonstrate that mPPIg5 is a highly effective anti-prion drug which acts, at least in part, through the inhibition of PrP(C) to PrP(Sc) conversion. Understanding how a drug works is a vital component in maximising its performance. By establishing the efficacy and method of action of mPPIg5, this study will help determine which drugs are most likely to enhance this effect and also aid the design of dendrimers with anti-prion capabilities for the future

Investigating local policy drivers for alcohol harm prevention: a comparative case study of two local authorities in England

Background: The considerable challenges associated with implementing national level alcohol policies have encouraged a renewed focus on the prospects for local-level policies in the UK and elsewhere. We adopted a case study approach to identify the major characteristics and drivers of differences in the patterns of local alcohol policies and services in two contrasting local authority (LA) areas in England. Methods: Data were collected via thirteen semi-structured interviews with key informants (including public health, licensing and trading standards) and documentary analysis, including harm reduction strategies and statements of licensing policy. A two-stage thematic analysis was used to categorize all relevant statements into seven over-arching themes, by which document sources were then also analysed. Results: Three of the seven over-arching themes (drink environment, treatment services and barriers and facilitators), provided for the most explanatory detail informing the contrasting policy responses of the two LAs: LA1 pursued a risk-informed strategy via a specialist police team working proactively with problem premises and screening systematically to identify riskier drinking. LA2 adopted a more upstream regulatory approach around restrictions on availability with less emphasis on co-ordinated screening and treatment measures. Conclusion: New powers over alcohol policy for LAs in England can produce markedly different policies for reducing alcohol-related harm. These difference are rooted in economic, opportunistic, organisational and personnel factors particular to the LAs themselves and may lead to closely tailored solutions in some policy areas and poorer co-ordination and attention in others

Fostering implementation of health services research findings into practice: a consolidated framework for advancing implementation science

Abstract Background Many interventions found to be effective in health services research studies fail to translate into meaningful patient care outcomes across multiple contexts. Health services researchers recognize the need to evaluate not only summative outcomes but also formative outcomes to assess the extent to which implementation is effective in a specific setting, prolongs sustainability, and promotes dissemination into other settings. Many implementation theories have been published to help promote effective implementation. However, they overlap considerably in the constructs included in individual theories, and a comparison of theories reveals that each is missing important constructs included in other theories. In addition, terminology and definitions are not consistent across theories. We describe the Consolidated Framework For Implementation Research (CFIR) that offers an overarching typology to promote implementation theory development and verification about what works where and why across multiple contexts. Methods We used a snowball sampling approach to identify published theories that were evaluated to identify constructs based on strength of conceptual or empirical support for influence on implementation, consistency in definitions, alignment with our own findings, and potential for measurement. We combined constructs across published theories that had different labels but were redundant or overlapping in definition, and we parsed apart constructs that conflated underlying concepts. Results The CFIR is composed of five major domains: intervention characteristics, outer setting, inner setting, characteristics of the individuals involved, and the process of implementation. Eight constructs were identified related to the intervention (e.g., evidence strength and quality), four constructs were identified related to outer setting (e.g., patient needs and resources), 12 constructs were identified related to inner setting (e.g., culture, leadership engagement), five constructs were identified related to individual characteristics, and eight constructs were identified related to process (e.g., plan, evaluate, and reflect). We present explicit definitions for each construct. Conclusion The CFIR provides a pragmatic structure for approaching complex, interacting, multi-level, and transient states of constructs in the real world by embracing, consolidating, and unifying key constructs from published implementation theories. It can be used to guide formative evaluations and build the implementation knowledge base across multiple studies and settings.http://deepblue.lib.umich.edu/bitstream/2027.42/78272/1/1748-5908-4-50.xmlhttp://deepblue.lib.umich.edu/bitstream/2027.42/78272/2/1748-5908-4-50-S1.PDFhttp://deepblue.lib.umich.edu/bitstream/2027.42/78272/3/1748-5908-4-50-S3.PDFhttp://deepblue.lib.umich.edu/bitstream/2027.42/78272/4/1748-5908-4-50-S4.PDFhttp://deepblue.lib.umich.edu/bitstream/2027.42/78272/5/1748-5908-4-50.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/78272/6/1748-5908-4-50-S2.PDFPeer Reviewe

Substance use outcomes following treatment : findings from the Australian Patient Pathways Study

Background and Aims: Our understanding of patient pathways through specialist Alcohol and Other Drug (AOD) treatment and broader health/welfare systems in Australia remains limited. This study examined how treatment outcomes are influenced by continuity in specialist AOD treatment, engagement with non-AOD community services, and mutual aid, as well as exploring differences between clients who present with a primary alcohol problem compared to those presenting with a primary drug issue. Method: In a prospective, multi-site treatment outcome study, 796 clients from 21 AOD services in Victoria and Western Australia completed a baseline interview between January 2012 and January 2013. 555 (70%) completed follow-up assessment of subsequent service use and AOD use outcomes 12-months later. Results: Just over half of the participants (52.0%) showed reliable reductions in use of, or abstinence from, their primary drug of concern. This was highest among clients who reported meth/amphetamine (66%) as their primary drug of concern and lowest among those who reported alcohol (47%), with 31% achieving abstinence from all drugs of concern. Continuity of specialist AOD care was associated with higher rates of abstinence than fragmented AOD care. Different predictors of treatment success emerged for clients with a primary drug problem as compared to those with a primary alcohol problem; mutual aid attendance (OR=2.5) and community service engagement (OR=2.0) for clients with alcohol as PDOC, and completion of the index treatment (OR=2.8) and continuity in AOD care (OR=1.8) for those with primary drug issues. Conclusion: This is the first multi-site Australian study to include treatment outcomes for alcohol and cannabis users, who represent 70% of treatment seekers in AOD services. The results suggest a substantial proportion of clients respond positively to treatment, but that clients with alcohol as their primary drug problem may require different treatment pathways, compared to those with illicit drug issues, to achieve desirable outcomes

Hierarchy Theory of Evolution and the Extended Evolutionary Synthesis: Some Epistemic Bridges, Some Conceptual Rifts

Contemporary evolutionary biology comprises a plural landscape of multiple co-existent conceptual frameworks and strenuous voices that disagree on the nature and scope of evolutionary theory. Since the mid-eighties, some of these conceptual frameworks have denounced the ontologies of the Modern Synthesis and of the updated Standard Theory of Evolution as unfinished or even flawed. In this paper, we analyze and compare two of those conceptual frameworks, namely Niles Eldredge’s Hierarchy Theory of Evolution (with its extended ontology of evolutionary entities) and the Extended Evolutionary Synthesis (with its proposal of an extended ontology of evolutionary processes), in an attempt to map some epistemic bridges (e.g. compatible views of causation; niche construction) and some conceptual rifts (e.g. extra-genetic inheritance; different perspectives on macroevolution; contrasting standpoints held in the “externalism–internalism” debate) that exist between them. This paper seeks to encourage theoretical, philosophical and historiographical discussions about pluralism or the possible unification of contemporary evolutionary biology

The effect of statin therapy on heart failure events: a collaborative meta-analysis of unpublished data from major randomized trials

The effect of statins on risk of heart failure (HF) hospitalization and HF death remains uncertain. We aimed to establish whether statins reduce major HF events.We searched Medline, EMBASE, and the Cochrane Central Register of Controlled Trials for randomized controlled endpoint statin trials from 1994 to 2014. Collaborating trialists provided unpublished data from adverse event reports. We included primary- and secondary-prevention statin trials with >1000 participants followed for >1 year. Outcomes consisted of first non-fatal HF hospitalization, HF death and a composite of first non-fatal HF hospitalization or HF death. HF events occurring <30 days after within-trial myocardial infarction (MI) were excluded. We calculated risk ratios (RR) with fixed-effects meta-analyses. In up to 17 trials with 132 538 participants conducted over 4.3 [weighted standard deviation (SD) 1.4] years, statin therapy reduced LDL-cholesterol by 0.97 mmol/L (weighted SD 0.38 mmol/L). Statins reduced the numbers of patients experiencing non-fatal HF hospitalization (1344/66 238 vs. 1498/66 330; RR 0.90, 95% confidence interval, CI 0.84-0.97) and the composite HF outcome (1234/57 734 vs. 1344/57 836; RR 0.92, 95% CI 0.85-0.99) but not HF death (213/57 734 vs. 220/57 836; RR 0.97, 95% CI 0.80-1.17). The effect of statins on first non-fatal HF hospitalization was similar whether this was preceded by MI (RR 0.87, 95% CI 0.68-1.11) or not (RR 0.91, 95% CI 0.84-0.98).In primary- and secondary-prevention trials, statins modestly reduced the risks of non-fatal HF hospitalization and a composite of non-fatal HF hospitalization and HF death with no demonstrable difference in risk reduction between those who suffered an MI or not

The cytotoxic T cell proteome and its shaping by the kinase mTOR

High-resolution mass spectrometry maps the cytotoxic T lymphocyte (CTL) proteome and the impact of mammalian target of rapamycin complex 1 (mTORC1) on CTLs. The CTL proteome was dominated by metabolic regulators and granzymes and mTORC1 selectively repressed and promoted expression of subset of CTL proteins (~10%). These included key CTL effector molecules, signaling proteins and a subset of metabolic enzymes. Proteomic data highlighted the potential for mTORC1 negative control of phosphatidylinositol (3,4,5)-trisphosphate (PtdIns(3,4,5)P(3)) production in CTL. mTORC1 was shown to repress PtdIns(3,4,5)P(3) production and to determine the mTORC2 requirement for activation of the kinase Akt. Unbiased proteomic analysis thus provides a comprehensive understanding of CTL identity and mTORC1 control of CTL function