Ages on weathered Plio-Pleistocene tephra sequences, western North Island, New Zealand

Using the zircon fission-track method, we have obtained five ages on members of two strongly-weathered silicic, Pliocene-Pleistocene tephra sequences, the Kauroa and Hamilton Ash formations, in western North Island, New Zealand. These are the first numerical ages to be obtained directly on these deposits. Of the Kauroa Ash sequence, member K1 (basal unit) was dated at 2.24 ± 0.29 Ma, confirming a previous age of c. 2.25 Ma obtained (via tephrochronology)from K/Ar ages on associated basalt lava. Members K2 and K3 gave indistinguishable ages between 1.68 ± 0.12 and 1.43 ± 0.17 Ma. Member K12, a correlative of Oparau Tephra and probably also Ongatiti Ignimbrite, was dated at 1.28 ± 0.11 Ma, consistent with an age of 1.23 ± 0.02 Ma obtained by various methods on Ongatiti Ignimbrite. Palaeomagnetic measurements indicated that members K13 to K15 (top unit, Waiterimu Ash) are aged between c. 1.2 Ma and 0.78 Ma. Possible sources of the Kauroa Ash Formation include younger volcanic centres in the southern Coromandel Volcanic Zone or older volcanic centres in the Taupo Volcanic Zone, or both. Of the Hamilton Ash sequence, the basal member Ohinewai Ash (HI) was dated at 0.38 ± 0.04 Ma. This age matches those obtained by various methods on Rangitawa Tephra of 0.34-0.35 Ma, supporting correlation with this Whakamaru-caldera derived deposit. The origin of the other Hamilton Ash beds is unknown but various younger volcanic centres in the Taupo Volcanic Zone are possible sources. The topmost member, Tikotiko Ash (H6-H7), is estimated to be aged between c. 0.18 and 0.08 Ma. Various silicic pyroclastic deposits documented in North Island and in marine cores may be co-eval with members of the Kauroa Ash and Hamilton Ash sequences on the basis of their age

Examining the impact of androgen deprivation therapy, masculine self-esteem, and psychological flexibility on distress and quality of life in men with prostate cancer

Objective: Studies suggest that androgen deprivation therapy (ADT) exacerbates psychological and quality of life (QoL) issues associated with prostate cancer (PCa). However, quantitative research examining underlying psychosocial mechanisms for this is limited. We examined the association of PCa symptoms with distress and QoL in ADT-treated and ADT-naïve patients, and the influence of masculine self-esteem and psychological flexibility (PF) on these relationships. Methods: Secondary analysis of a quantitative, cross-sectional survey of 286 PCa patients. Independent samples t-tests, moderation, and conditional process analysis were used to assess relationships between predictor, mediator, moderator, and outcome variables. Results: ADT was associated with greater PCa symptomology, lower masculine self-esteem, and lower QoL. Moderation analysis showed that ADT potentiated adverse impacts of PCa symptomology on distress and QoL. High PF attenuated these relationships, though less so for ADT-treated participants. Conditional process analysis showed that masculine self-esteem mediated the predictive effect of symptoms on distress across treatments. However, ADT did not moderate this indirect effect, nor was moderation conditional on PF. Conclusion: PF appears to: (1) attenuate psychological distress in ADT patients; and (2) improve distress, QoL, and masculine self-esteem in ADT-naïve patients. Interventions targeting PF may thus be a viable adjunct to established approaches. However, their effects may be comparatively limited in ADT patients, who may benefit from more intensive and tailored treatment.</p

Consequence-based Reasoning for Description Logics with Disjunction, Inverse Roles, Number Restrictions, and Nominals

We present a consequence-based calculus for concept subsumption and classification in the description logic ALCHOIQ, which extends ALC with role hierarchies, inverse roles, number restrictions, and nominals. By using standard transformations, our calculus extends to SROIQ, which covers all of OWL 2 DL except for datatypes. A key feature of our calculus is its pay-as-you-go behaviour: unlike existing algorithms, our calculus is worst-case optimal for all the well-known proper fragments of ALCHOIQ, albeit not for the full logic

Predictive properties of risk assessment instruments following self-harm.

This month's BJPsych publishes two important studies concerned with the use of risk assessment scales after self-harm, one a systematic review and the other a multicentre cohort study. We agree with the authors: that each study adds weight to the existing evidence that points towards avoiding the use of such scales in clinical practice

Determining the location of the α-synuclein dimer Interface using native top-down fragmentation and isotope depletion-mass spectrometry

α-Synuclein (αSyn), a 140-residue intrinsically disordered protein, comprises the primary proteinaceous component of pathology-associated Lewy body inclusions in Parkinson’s disease (PD). Due to its association with PD, αSyn is studied extensively; however, the endogenous structure and physiological roles of this protein are yet to be fully understood. Here, ion mobility-mass spectrometry and native top-down electron capture dissociation fragmentation have been used to elucidate the structural properties associated with a stable, naturally occurring dimeric species of αSyn. This stable dimer appears in both wild-type (WT) αSyn and the PD-associated variant A53E. Furthermore, we integrated a novel method for generating isotopically depleted protein into our native top-down workflow. Isotope depletion increases signal-to-noise ratio and reduces the spectral complexity of fragmentation data, enabling the monoisotopic peak of low abundant fragment ions to be observed. This enables the accurate and confident assignment of fragments unique to the αSyn dimer to be assigned and structural information about this species to be inferred. Using this approach, we were able to identify fragments unique to the dimer, which demonstrates a C-terminal to C-terminal interaction between the monomer subunits. The approach in this study holds promise for further investigation into the structural properties of endogenous multimeric species of αSyn

Alpha-Synuclein Oligomers Interact with Metal Ions to Induce Oxidative Stress and Neuronal Death in Parkinson's Disease

Protein aggregation and oxidative stress are both key pathogenic processes in Parkinson's disease, although the mechanism by which misfolded proteins induce oxidative stress and neuronal death remains unknown. In this study, we describe how aggregation of alpha-synuclein (α-S) from its monomeric form to its soluble oligomeric state results in aberrant free radical production and neuronal toxicity

Single-molecule FRET studies on alpha-synuclein oligomerization of Parkinson's disease genetically related mutants.

Oligomers of alpha-synuclein are toxic to cells and have been proposed to play a key role in the etiopathogenesis of Parkinson's disease. As certain missense mutations in the gene encoding for alpha-synuclein induce early-onset forms of the disease, it has been suggested that these variants might have an inherent tendency to produce high concentrations of oligomers during aggregation, although a direct experimental evidence for this is still missing. We used single-molecule Förster Resonance Energy Transfer to visualize directly the protein self-assembly process by wild-type alpha-synuclein and A53T, A30P and E46K mutants and to compare the structural properties of the ensemble of oligomers generated. We found that the kinetics of oligomer formation correlates with the natural tendency of each variant to acquire beta-sheet structure. Moreover, A53T and A30P showed significant differences in the averaged FRET efficiency of one of the two types of oligomers formed compared to the wild-type oligomers, indicating possible structural variety among the ensemble of species generated. Importantly, we found similar concentrations of oligomers during the lag-phase of the aggregation of wild-type and mutated alpha-synuclein, suggesting that the properties of the ensemble of oligomers generated during self-assembly might be more relevant than their absolute concentration for triggering neurodegeneration.LT has been recipient of a grant PAT Post Doc Outgoing 2009 – 7th Framework Program Marie Curie COFUND actions. NC was funded by a Royal Society Dorothy Hodgkin Research Fellowship and is currently a Ramón y Cajal Research Fellow (Spanish Ministry of Economy and Competitiveness). MHH thanks the Royal Society of Chemistry (Analytical Chemistry Trust Fund) for his studentship. AJD is funded by the Schiff Foundation.This is the final version of the article. It first appeared from NPG via http://dx.doi.org/10.1038/srep1669

GALA: an international multicentre randomised trial comparing general anaesthesia versus local anaesthesia for carotid surgery

Background: Patients who have severe narrowing at or near the origin of the internal carotid artery as a result of atherosclerosis have a high risk of ischaemic stroke ipsilateral to the arterial lesion. Previous trials have shown that carotid endarterectomy improves long-term outcomes, particularly when performed soon after a prior transient ischaemic attack or mild ischaemic stroke. However, complications may occur during or soon after surgery, the most serious of which is stroke, which can be fatal. It has been suggested that performing the operation under local anaesthesia, rather than general anaesthesia, may be safer. Therefore, a prospective, randomised trial of local versus general anaesthesia for carotid endarterectomy was proposed to determine whether type of anaesthesia influences peri-operative morbidity and mortality, quality of life and longer term outcome in terms of stroke-free survival. Methods/design: A two-arm, parallel group, multicentre randomised controlled trial with a recruitment target of 5000 patients. For entry into the study, in the opinion of the responsible clinician, the patient requiring an endarterectomy must be suitable for either local or general anaesthesia, and have no clear indication for either type. All patients with symptomatic or asymptomatic internal carotid stenosis for whom open surgery is advised are eligible. There is no upper age limit. Exclusion criteria are: no informed consent; definite preference for local or general anaesthetic by the clinician or patient; patient unlikely to be able to co-operate with awake testing during local anaesthesia; patient requiring simultaneous bilateral carotid endarterectomy; carotid endarterectomy combined with another operation such as coronary bypass surgery; and, the patient has been randomised into the trial previously. Patients are randomised to local or general anaesthesia by the central trial office. The primary outcome is the proportion of patients alive, stroke free ( including retinal infarction) and without myocardial infarction 30 days post-surgery. Secondary outcomes include the proportion of patients alive and stroke free at one year; health related quality of life at 30 days; surgical adverse events, re-operation and re-admission rates; the relative cost of the two methods of anaesthesia; length of stay and intensive and high dependency bed occupancy