The interaction of relativistically intense lasers with opaque targets represents a highly non-linear, multi-dimensional parameter space. This limits the utility of sequential 1D scanning of experimental parameters for the optimization of secondary radiation, although to-date this has been the accepted methodology due to low data acquisition rates. High repetition-rate (HRR) lasers augmented by machine learning present a valuable opportunity for efficient source optimization. Here, an automated, HRR-compatible system produced high-fidelity parameter scans, revealing the influence of laser intensity on target pre-heating and proton generation. A closed-loop Bayesian optimization of maximum proton energy, through control of the laser wavefront and target position, produced proton beams with equivalent maximum energy to manually optimized laser pulses but using only 60% of the laser energy. This demonstration of automated optimization of laser-driven proton beams is a crucial step towards deeper physical insight and the construction of future radiation sources.

We present the development and characterization of a high-stability, multi-material, multi-thickness tape-drive target for laser-driven acceleration at repetition rates of up to 100 Hz. The tape surface position was measured to be stable on the sub-micrometre scale, compatible with the high-numerical aperture focusing geometries required to achieve relativistic intensity interactions with the pulse energy available in current multi-Hz and near-future higher repetition-rate lasers ($>$kHz). Long-term drift was characterized at 100 Hz demonstrating suitability for operation over extended periods. The target was continuously operated at up to 5 Hz in a recent experiment for 70,000 shots without intervention by the experimental team, with the exception of tape replacement, producing the largest data-set of relativistically intense laser–solid foil measurements to date. This tape drive provides robust targetry for the generation and study of high-repetition-rate ion beams using next-generation high-power laser systems, also enabling wider applications of laser-driven proton sources.

Twenty-four new optically stimulated luminescence (OSL) and radiocarbon ages from sediment cores in nine lakes associated with the Shipshewana and Sturgis moraines in northern Indiana and southern Michigan estimate when recession of the Saginaw Lobe of the Laurentide Ice Sheet was underway in the southern Great Lakes region, USA. Average OSL ages of 23.4 ± 2.2 ka for the Shipshewana Moraine and 19.7 ± 2.2 ka for the Sturgis Moraine are considered minimum limiting deglacial ages for these recessional moraines. The much younger radiocarbon ages are consistent with other regional radiocarbon ages from lakes, and record climate amelioration around ~16.5 cal ka BP. Early recession of the interlobate Saginaw Lobe was well underway by 23.4 ± 2.2 ka, when the adjacent Lake Michigan and Huron-Erie lobes were a few hundred kilometers farther south and near their maximum southerly limits. The results provide the first time constraints when sediment from the Lake Michigan and Huron-Erie lobes began filling the accommodation space left by the Saginaw Lobe. The difference between the oldest radiocarbon and OSL age is 7400 yr for the Shipshewana Moraine and 3400 yr for the Sturgis Moraine.

Living systems exert exquisite control on all aspects of biomineral production and organic components, including proteins, are essential to this biological control. The protein-rich extrapallial (EP) fluid of bivalve molluscs is a strong candidate for the source of such proteins. Differences in calcium carbonate polymorphs between Modiolus modiolus and Mytilus edulis are concurrent with differences in EP fluid protein profiles. In conjunction with this biological control is the environmental influence which is interpreted using proxies such as δ18O to determine the history of ambient seawater temperature. In the horse mussel, Modiolus modiolus, the difference in oxygen isotope fractionation in the nacreous aragonite and the prismatic aragonite layer results in respective δ18O values of 2.1±0.2% and 2.5±0.2%. These δ18O values result in estimates of ambient seawater of 12.1±0.6°C and 10.2±0.6°C for nacreous and prismatic aragonite, respectively. Electron backscatter diffraction is used here to determine the crystallographic orientation at high spatial resolution, allowing the measurements of stable isotopes to be accurately mapped in terms of shell architecture. These preliminary data suggest that it is essential to account for both polymorph and crystal habit when deciphering ambient seawater temperature using δ18O as a proxy.

Oxygen- and carbon-isotopic analyses have been performed on the benthic foraminifer Planulina wuellerstorfi in seven Late Quaternary cores from the Vema Channel-Rio Grande Rise region. The cores are distributed over the water-depth interval of 2340 to 3939 m, which includes the present transition from North Atlantic Deep Water (NADW) to Antarctic Bottom Water (AABW).

The carbon-isotopic records in the cores vary as a function of water depth. The shallowest and deepest cores show no significant glacial-interglacial difference in δ13C. Four of the five cores presently located in the NADW have benthic foraminiferal δ13C that is lower during glacial isotopic stages. Based on bathymetric gradients in δ13C, we conclude that, like today, there were two water masses present in the Vema Channel during glacial intervals: a water mass enriched in 13C overlying another water mass depleted in 13C. The largest gradient of change of δ13C with depth, however, occurred at 2.7 km, ∼ 1 km shallower than the present position of this gradient.

On the basis of paleontologic and sedimentologic evidence, we consider it unlikely that the NADW:AABW transition shallowed to this level. Reduced carbon-isotopic gradients between the deep basins of the North Atlantic and Pacific Oceans during the last glaciation suggest that production of NADW was reduced. Lower production of NADW may have modified the local abyssal circulation pattern in the Vema Channel region.

Much can be learned from terrestrial planets that appear to have had the potential to be habitable, but failed to realize that potential. Mars shows evidence of a once hospitable surface environment. The reasons for its current state, and in particular its thin atmosphere and dry surface, are of great interest for what they can tell us about habitable zone planet outcomes. A main goal of the MAVEN mission is to observe Mars’ atmosphere responses to solar and space weather influences, and in particular atmosphere escape related to space weather ‘storms’ caused by interplanetary coronal mass ejections (ICMEs). Numerical experiments with a data-validated MHD model suggest how the effects of an observed moderately strong ICME compare to what happens during a more extreme event. The results suggest the kinds of solar and space weather conditions that can have evolutionary importance at a planet like Mars.

The Darwin region in northern Australia has experienced rapid population growth in recent years, and with it, an increased incidence of melioidosis. Previous studies in Darwin have associated the environmental presence of Burkholderia pseudomallei, the causative agent of melioidosis, with anthropogenic land usage and proximity to animals. In our study, we estimated the occurrence of B. pseudomallei and Burkholderia spp. relatives in faecal matter of wildlife, livestock and domestic animals in the Darwin region. A total of 357 faecal samples were collected and bacteria isolated through culture and direct DNA extraction after enrichment in selective media. Identification of B. pseudomallei, B. ubonensis, and other Burkholderia spp. was carried out using TTS1, Bu550, and recA BUR3–BUR4 quantitative PCR assays, respectively. B. pseudomallei was detected in seven faecal samples from wallabies and a chicken. B. cepacia complex spp. and Pandoraea spp. were cultured from wallaby faecal samples, and B. cenocepacia and B. cepacia were also isolated from livestock animals. Various bacteria isolated in this study represent opportunistic human pathogens, raising the possibility that faecal shedding contributes to the expanding geographical distribution of not just B. pseudomallei but other Burkholderiaceae that can cause human disease.

The distribution of Burkholderia pseudomallei was determined in soil collected from a rural district in Papua New Guinea (PNG) where melioidosis had recently been described, predominately affecting children. In 274 samples, 2·6% tested culture-positive for B. pseudomallei. Pulsed-field gel electrophoresis using SpeI digests and rapid polymorphic DNA PCR with five primers demonstrated a single clone amongst clinical isolates and isolates cultured from the environment that was commonly used by children from whom the clinical isolates were derived. We concluded that individuals in this region most probably acquired the organism through close contact with the environment at these sites. Burkholderia thailandensis, a closely related Burkholderia sp. was isolated from 5·5% of samples tested, an observation similar to that of melioidosis-endemic areas in Thailand. This is the first report of an environmental reservoir for melioidosis in PNG and confirms the Balimo district in PNG as melioidosis endemic.

We observed an outbreak of necrotizing fasciitis associated with Streptococcus agalactiae infection in a group of juvenile saltwater crocodiles (Crocodylus porosus). We undertook screening of crocodiles and the environment to clarify the source of the outbreak and evaluated the isolates cultured from post-mortem specimens with molecular methods to assess clonality and the presence of known group B streptococcal virulence determinants. The isolates were indistinguishable by pulsed-field gel electrophoresis. They were a typical serotype Ia strain with the Cα-like protein gene, epsilon (or alp1), the mobile genetic elements IS381 ISSag1 and ISSag2, and belonged to multi-locus sequence type (ST) 23. All of these characteristics suggest they were probably of human origin. We review the medical and veterinary literature relating to S. agalactiae necrotizing fasciitis, epidemiology and virulence determinants.

In November 2002, the first of three outbreaks of Salmonella Montevideo infection in Australia and New Zealand was identified in New South Wales, Australia. Affected persons were interviewed, and epidemiologically linked retail outlets inspected. Imported tahini was rapidly identified as the source of infection. The contaminated tahini was recalled and international alerts posted. A second outbreak was identified in Australia in June–July 2003 and another in New Zealand in August 2003. In a total of 68 S. Montevideo infections, 66 cases were contacted. Fifty-four (82%) reported consumption of sesame seed-based foods. Laboratory analyses demonstrated closely related PFGE patterns in the S. Montevideo isolates from human cases and sesame-based foods imported from two countries. On the basis of our investigations sesame-based products were sampled in other jurisdictions and three products in Canada and one in the United Kingdom were positive for Salmonella spp., demonstrating the value of international alerts when food products have a wide distribution and a long shelf life. A review of the controls for Salmonella spp. during the production of sesame-based products is recommended.

Chronic tendon lesions are degenerative conditions and may represent a failure to repair or remodel the extracellular matrix after repeated micro-injury. Since TGF-β is strongly associated with tissue repair, we investigated the expression of TGF-β isoforms (β1, β2 and β3) and their 2 signalling receptors (TGF-βRI and TGF-βRII) in normal and pathological Achilles tendons. In all tissues, all 3 TGF-β isoforms and the 2 receptors were present at sites of blood vessels. Cells in the matrix showed no staining for TGF-β1 or β3, while TGF-β2 was associated with cells throughout the normal cadaver tendon. Tissue from tendons with pathological lesions showed an increase in cell numbers and percentage TGF-β2 expression. TGF-βRII showed a wide distribution in cells throughout the tissue sections. As with TGF-β2, there was an increase in the number of cells expressing TGF-βRII in pathological tissue. TGF-βRI was restricted to blood vessels and was absent from the fibrillar matrix. We conclude that despite the presence and upregulation of TGF-β2, TGF-β signalling is not propagated due to the lack of TGF-βRI. This might explain why chronic tendon lesions fail to resolve and suggests that the addition of exogenous TGF-β will have little effect on chronic tendinopathy.

We present an overview of recent multidisciplinary, multi-institutional efforts to identify and date major sources of combustion aerosol in the current and paleoatmospheres. The work was stimulated, in part, by an atmospheric particle “sample of opportunity” collected at Summit, Greenland in August 1994, that bore the 14C imprint of biomass burning. During the summer field seasons of 1995 and 1996, we collected air filter, surface snow and snowpit samples to investigate chemical and isotopic evidence of combustion particles that had been transported from distant fires. Among the chemical tracers employed for source identification are organic acids, potassium and ammonium ions, and elemental and organic components of carbonaceous particles. Ion chromatography, performed by members of the Climate Change Research Center (University of New Hampshire), has been especially valuable in indicating periods at Summit that were likely to have been affected by the long range transport of biomass burning aerosol. Univariate and multivariate patterns of the ion concentrations in the snow and ice pinpointed surface and snowpit samples for the direct analysis of particulate (soot) carbon and carbon isotopes. The research at NIST is focusing on graphitic and polycyclic aromatic carbon, which serve as almost certain indicators of fire, and measurements of carbon isotopes, especially 14C, to distinguish fossil and biomass combustion sources.

Complementing the chemical and isotopic record, are direct “visual” (satellite imagery) records and less direct backtrajectory records, to indicate geographic source regions and transport paths. In this paper we illustrate the unique way in which the synthesis of the chemical, isotopic, satellite and trajectory data enhances our ability to develop the recent history of the formation and transport of soot deposited in the polar snow and ice.

When 14C signals approach background levels, the validity of assumptions concerning Poisson counting statistics and measurement system stability becomes crucial in interpreting the resultant low-level counting observations. This has been demonstrated in our previous work on detection limits for non-Poisson error and it is critical in our current studies of carbonaceous pollutants, where the 14C signal from just 5 mg C is comparable to that of the background for our miniature gas proportional counters. To assure data quality, our multi-detector system is designed for the on-line monitoring of critical parameters that reflect both the (statistical) nature of the non-Poisson errors and the underlying (physical) causes. It sends >60 bits of information/pulse to a microprocessor which automatically generates, for each counting period, two-dimensional spectra and multiparameter correlation and control charts. To evaluate the validity of long-term counting of 1–10 mg C we use robust (statistical) estimators, optimal counting interval subdivision, and time series analysis of the individual pulses. New opportunities for selective sampling and chemical fractionation which come with the small sample measurement capability have led us to give special attention also to higher control levels, involving e g, isotonic heterogeneity and representative standard materials.

Cyclizine hydrochloride (1-benzhydryl-4-methylpiperazine monohydrochloride) is a popular remedy for motion-sickness. The success which is reputed to attend the use of the drug in this condition may be a function of of two distinct effects: (a) a direct, specific inhibition of the vestibular mechanism; (b) a general, central inhibition or sedation. A consideration of the latter, rather than the former, suggested the possibility that cyclizine might prove to be of value as a potential “tranquillizer”. A controlled clinical trial was carried out in order to establish whether any tranquillizing effects might be associated with the use of the drug in a number of chronic psychotics, all of whom manifested some gross disturbance of behaviour. This paper describes the experimental method which was used; the results which were obtained; and a general comment upon the possible implications of the results in relation to other drugs used in psychiatry.

The discovery of chlorpromazine in the Rhône-Poulenc-Spécia laboratories in France, and the subsequent early clinical studies which were carried out in that country, for example in 1952 by Hamon et al. (5) and in 1953 by Delay and Deniker (1), eventually resulted in the enthusiastic and widespread application of this compound in the field of clinical psychiatry. Chemists and pharmacologists, in many countries, have been actively engaged during the ensuing years in the search for new compounds which might prove to be more potent therapeutic agents than chlorpromazine in the treatment of mental illness. One of the tangible manifestations of their labours is the present crop of “tranquillizers” which are being extensively used in the treatment of neurosis and psychosis. Whereas opinion may be divided with regard to the real or specific value of any one of these new drugs, few would disagree with the contention that none of them is ideal. Despite the considerable number and variety of phenothiazine derivatives and other new substances which have been developed as a result of extensive research, chlorpromazine has retained much of its original therapeutic reputation, in open competition with its rivals, down the years, and is still probably the most widely used tranquillizer today. This would seem to imply that no outstanding advance has been made since the early days of the new biochemical era in psychiatry. Valuable knowledge may have been obtained as a result of the application of scientific theory and empirical methods in this field, but in terms of effective therapeutic agents the results have been meagre, with the accent on quantity rather than quality. Nevertheless, a continued search is justifiable, and any new compound which holds forth promise must be put to a clinical test if final success is to be assured and if valuable therapeutic potential is not to be summarily dismissed or heedlessly cast aside.