Fossil shark teeth from upland Fleurieu Peninsula, South Australia: evidence for previously unknown Tertiary marine sediments

Neville S Pledge, Anthony R Milnes, Robert P Bourman, and Neville F Alle

Olaparib for Maintenance Treatment of BRCA 1 or 2 Mutated, Relapsed, Platinum-Sensitive Ovarian, Fallopian Tube and Peritoneal Cancer in People Whose Relapsed Disease has Responded to Platinum-Based Chemotherapy: An Evidence Review Group Perspective of a NICE Single Technology Appraisal

As part of its Single Technology Appraisal process, the National Institute for Health and Care Excellence (NICE) invited the manufacturer of olaparib (AstraZeneca) to submit evidence on the clinical and cost effectiveness of olaparib for the maintenance treatment of BRCA1/2 mutated (BRCAm), platinum-sensitive relapsed (PSR) ovarian, fallopian tube and peritoneal cancer in people whose relapsed disease has responded to platinum-based chemotherapy. The Evidence Review Group (ERG) produced a critical review of the evidence contained within the company’s submission (CS) to NICE. The clinical evidence related to one phase II, double-blind randomised controlled trial that recruited 265 patients with PSR serous ovarian cancer (OC) regardless of BRCAm status. Patients received olaparib 400 mg twice daily (b.i.d.) or matched placebo. In the whole population, the primary endpoint of progression-free survival (PFS) was met (hazard ratio [HR] 0.35; 95 % confidence interval [CI] 0.25–0.49, p < 0.01) for olaparib versus placebo. The BRCAm subgroup analysis (added after the study commenced but 1 month before the primary analysis was undertaken) reported an HR for PFS of 0.18 (95 % CI 0.10–0.31, p < 0.0001) for olaparib versus placebo, though interaction tests appeared inconclusive. Overall survival was not statistically significant in the whole group (HR 0.88; 95 % CI 0.64–1.21; p = 0.44) or the BRCAm subgroup (0.73; 95 % CI 0.45–1.17; p = 0.19), though treatment switching may have confounded results. The exclusion of data from sites allowing crossover resulted in an HR for overall survival (OS) of 0.52 (95 % CI 0.28–0.97, p = 0.039) in the BRCAm group. Health-related quality-of-life measures were not significantly different between groups. All post hoc exploratory outcomes (time to treatment discontinuation/death, time to first subsequent therapy/death, and time to second subsequent therapy/death) were statistically significantly better in the olaparib arm in the whole population and the BRCAm subgroup analyses. Adverse events were more frequent for olaparib but were largely minor or manageable. The company’s semi-Markov model assessed the cost effectiveness of olaparib versus routine surveillance in patients with BRCAm PSR OC from a National Health Service (NHS) and Personal Social Services (PSS) perspective over a lifetime horizon. The model suggests that the incremental cost-effectiveness ratio (ICER) for olaparib versus routine surveillance is expected to be approximately £49,146 per quality-adjusted life-year (QALY) gained. The ERG did not consider the company’s cost-effectiveness estimates to be credible. Additional ERG analyses suggested that the ICER is likely to be more than £92,214 per QALY gained. Additional analyses provided by the company in patients who received three or more lines of chemotherapy suggested a more favourable cost-effectiveness profile for olaparib. The NICE Appraisal Committee recommended olaparib for this subgroup provided the cost of olaparib for people who continue to receive treatment after 15 months will be met by the company

The differential hormonal milieu of morning versus evening, may have an impact on muscle hypertrophic potential

Substantial gains in muscle strength and hypertrophy are clearly associated with the routine performance of resistance training. What is less evident is the optimal timing of the resistance training stimulus to elicit these significant functional and structural skeletal muscle changes. Therefore, this investigation determined the impact of a single bout of resistance training performed either in the morning or evening upon acute anabolic signalling (insulin-like growth factor-binding protein-3 (IGFBP-3), myogenic index and differentiation) and catabolic processes (cortisol). Twenty-four male participants (age 21.4±1.9yrs, mass 83.7±13.7kg) with no sustained resistance training experience were allocated to a resistance exercise group (REP). Sixteen of the 24 participants were randomly selected to perform an additional non-exercising control group (CP) protocol. REP performed two bouts of resistance exercise (80% 1RM) in the morning (AM: 0800 hrs) and evening (PM: 1800 hrs), with the sessions separated by a minimum of 72 hours. Venous blood was collected immediately prior to, and 5 min after, each resistance exercise and control sessions. Serum cortisol and IGFBP-3 levels, myogenic index, myotube width, were determined at each sampling period. All data are reported as mean ± SEM, statistical significance was set at P≤0.05. As expected a significant reduction in evening cortisol concentration was observed at pre (AM: 98.4±10.5, PM: 49.8±4.4 ng/ml, P0.05). Timing of resistance training regimen in the evening appears to augment some markers of hypertrophic potential, with elevated IGFBP-3, suppressed cortisol and a superior cellular environment. Further investigation, to further elucidate the time course of peak anabolic signalling in morning vs evening training conditions, are timely

THE OCCURRENCE OF A DIPROTODONTID MARSUPIAL REFERABLE TO EUOWENIA-GRATA NEW-RECORD DE VIS IN WESTERN NEW SOUTH WALES AUSTRALIA

Volume: 113Start Page: 163End Page: 16

FOSSIL ELASMOBRANCH TEETH OF SOUTH AUSTRALIA AND THEIR STRATIGRAPHIC DISTRIBUTION CARCHARIAS-MASLINENSIS NEW SPECIES

Volume: 91Start Page: 135End Page: 16

A NEW SUBSPECIES OF THE SEA URCHIN PERONELLA-LESUEURI FROM THE QUATERNARY OF SOUTH AUSTRALIA

Volume: 114Start Page: 103End Page: 10

A Shelduck (Anatidae: Tadorna) from the Pliocene of South Australia

Volume: 131Start Page: 107End Page: 11

The oldest genus of scincid lizard (Squamata) from the tertiary etadunna formation of South Australia

Recent expeditions to the Lake Palankarinna area of South Australia resulted in the oldest and only known extinct skink genus in Australia. The holotype of a new genus and species, Proegernia palankarinnensis, was collected from the basal portion of the Late Oligocene Etadunna Formation from the Minkina Local Fauna. Additional scincid fossils previously recovered from higher levels in the formation include material that may be referable to Proegernia. Proegernia is placed in the Egernia group within the Australian Lygosominae, based mainly on its closed Meckelian groove with the apex of the splenial notch low on the lingual surface. However, the apex is markedly more anterior in Proegernia than in any living Egernia group taxon. Proegernia possesses characters suggestive of its position as a stem taxon for later occurring skinks of the Egernia species groups. Even so, overall stage of evolution suggests that the Scincidae of Australia had a long evolutionary history prior to the Late Oligocene, a contention supported by previous molecular studies.James E. Martin, Mark N. Hutchinson, Robert Meredith, Judd A. Case, and Neville S. Pledg

A late Pleistocene occurrence of Diprotodon at Hallett Cove, South Australia

Volume: 126Start Page: 39End Page: 4