Aqueously altered igneous rocks sampled on the floor of Jezero crater, Mars.

The Perseverance rover landed in Jezero crater, Mars, to investigate ancient lake and river deposits. We report observations of the crater floor, below the crater's sedimentary delta, finding that the floor consists of igneous rocks altered by water. The lowest exposed unit, informally named Séítah, is a coarsely crystalline olivine-rich rock, which accumulated at the base of a magma body. Magnesium-iron carbonates along grain boundaries indicate reactions with carbon dioxide-rich water under water-poor conditions. Overlying Séítah is a unit informally named Máaz, which we interpret as lava flows or the chemical complement to Séítah in a layered igneous body. Voids in these rocks contain sulfates and perchlorates, likely introduced by later near-surface brine evaporation. Core samples of these rocks have been stored aboard Perseverance for potential return to Earth.

Progression-free survival as a clinical trial endpoint in advanced renal cell carcinoma.

Traditionally, overall survival (os) has been considered the "gold standard" for evaluating new systemic oncologic therapies, because death is easy to define, is easily compared across disease sites, and is not subject to investigator bias. However, as the available options for continuing therapy increase, the use of os as a clinical trial endpoint has become problematic because of the increasing crossover and contamination of trials. As a result, the approval of promising new therapies may be delayed.Many clinicians believe that progression-free survival (pfs) is a more viable option for evaluating new therapies in metastatic and advanced renal cell carcinoma. As with all endpoints, pfs has inherent biases, and those biases must be addressed to ensure that trial results are not compromised and that they will be accepted by regulatory authorities. In this paper, we examine the issues surrounding the use of pfs as a clinical trial endpoint, and we suggest solutions to ensure that data integrity is maintained.

Microscale imaging and identification of Fe speciation and distribution during fluid-mineral reactions under highly reducing conditions.

The oxidation state, speciation, and distribution of Fe are critical determinants of Fe reactivity in natural and engineered environments. However, it is challenging to follow dynamic changes in Fe speciation in environmental systems during progressive fluid-mineral interactions. Two common geological and aquifer materials-basalt and Fe(III) oxides-were incubated with saline fluids at 55 °C under highly reducing conditions maintained by the presence of Fe(0). We tracked changes in Fe speciation after 48 h (incipient water-rock reaction) and 10 months (extensive water-rock interaction) using synchrotron-radiation µXRF maps collected at multiple energies (ME) within the Fe K-edge. Immediate PCA analysis of the ME maps was used to optimize µXANES analyses; in turn, refitting the ME maps with end-member XANES spectra enabled us to detect and spatially resolve the entire variety of Fe-phases present in the system. After 48 h, we successfully identified and mapped the major Fe-bearing components of our samples (Fe(III) oxides, basalt, and rare olivine), as well as small quantities of incipient brucite associated with olivine. After 10 months, the Fe(III)-oxides remained stable in the presence of Fe(0), whereas significant alteration of basalt to minnesotaite and chlinochlore had occurred, providing new insights into heterogeneous Fe speciation in complex geological media under highly reducing conditions.

High-intensity focused ultrasound for prostate cancer: a systematic review.

High-intensity focused ultrasound (HIFU) has recently been promoted as a non-invasive treatment option for prostate cancer. This systematic review sought to evaluate the evidence comparing it with standard treatment in patients with localised prostate cancer. The literature review included searches of MEDLINE, EMBASE, the Cochrane Library, annual meetings' abstracts and websites of evidence-based practice guideline producers. Studies were included if they were randomised controlled trials comparing HIFU with current management approaches, or were meta-analyses, systematic reviews or practice guidelines addressing HIFU. No randomised controlled trials or meta-analyses were identified. Seven systematic reviews and two practice guidelines were identified; neither contained randomised controlled trials. Adjusting the selection criteria to include case series found 34 clinical studies of HIFU. Twenty-nine evaluated HIFU as the primary treatment and five examined HIFU as salvage treatment for recurrence after radiotherapy. In most studies the outcomes used to determine efficacy were negative biopsy rates or prostate-specific antigen (PSA) levels. Among the 29 studies of HIFU as the primary treatment, negative biopsy rates ranged from 35 to 95% in 21 studies, a PSA nadir of ≤0.5 ng/ml ranged from 55 to 91% in 10 studies and mean PSA nadirs ranged from 0 to 1.9 ng/ml in 17 studies. Five studies reported 5-year disease-free survival rates ranging from 55 to 95%. Among five studies of HIFU as salvage treatment, negative biopsy rates ranged from 73 to 84% in four studies, a PSA nadir of ≤0.5 ng/ml ranged from 57 to 66% in three studies and mean PSA nadirs were 1.97 and 2.38 ng/ml in two studies, respectively. Current evidence on HIFU use in prostate cancer patients is of low quality, rendering it difficult to draw conclusions about its efficacy. Until results from case series are confirmed in prospective studies, the widespread use of HIFU is not supported.

Management of stage I non-seminomatous testicular cancer: a systematic review and meta-analysis.

After orchidectomy and staging, patients with clinical stage I (CS I) non-seminomatous testicular cancer (NSTC) may be offered chemotherapy, surgery or active surveillance. The optimal postoperative approach is undefined. Therefore, a systematic review was carried out to assess these management approaches. Eligible studies, systematic reviews and clinical practice guidelines included patients with CS I NSTC or a mixed seminoma/non-seminoma diagnosis. The primary outcomes of interest included cancer cure, long-term toxicity and quality of life. In total, 32 unique reports met the selection criteria. Cancer cure rates were excellent regardless of the management option selected. Overall and disease-free survival rates were over 95% for all management approaches; recurrence rates were higher in the patients managed by surveillance. In conclusion, patients with CS I NSTC should be assessed and managed at multidisciplinary centres by health care professionals experienced in the treatment of testicular cancer. On the basis of the available evidence, the Genitourinary Disease Site Group recommended primary surveillance for all patients with CS I NSTC, with treatment if relapse occurs. As cancer cure rates are similar with primary surveillance, adjuvant chemotherapy and retroperitoneal lymphadenectomy, patient preference with respect to the risk of recurrence and the timing and toxicities of treatment must be considered. For patients who prefer immediate treatment, or who are unsuitable for primary surveillance, adjuvant chemotherapy with two cycles of bleomycin, etoposide (500mg/m(2)/cycle) and cisplatin was recommended. Surgeons involved in the development of this guideline suggested that retroperitoneal lymphadenectomy may be a useful option for patients at high risk of relapse. There is currently insufficient evidence from prospective trials to support or refute this position.

Management of stage I seminomatous testicular cancer: a systematic review.

The treatment options available for the management of stage I seminoma consist of either a surveillance strategy or adjuvant therapy after orchidectomy. A systematic review was undertaken to identify the optimal management strategy. The MEDLINE and EMBASE databases, in addition to the American Society of Clinical Oncology Meeting Proceedings, were searched for the period 1981 to May 2007. Studies were eligible for inclusion if they discussed at least one of survival, recurrence, second malignancy, cardiac toxicity, or quality of life for patients with stage I seminoma. A search update was carried out in June 2009. Fifty-four reports satisfied the eligibility criteria, including seven clinical practice guidelines, one systematic review, three randomised controlled trials focused on treatment options, 26 non-randomised studies of treatment options, and 15 non-randomised long-term toxicity studies. The existing data suggest that virtually all patients with stage I testicular seminoma are cured regardless of the post-orchidectomy management. The 5-year survival reported in all the studies identified in this systematic review was over 95%, regardless of the management strategy, including surveillance alone with no adjuvant therapy. In conclusion, to date, the optimal management of stage I seminoma remains to be defined. Surveillance seems to be the preferable option, as this strategy minimises the toxicity that might be associated with adjuvant treatment, while preserving high long-term cure rates. The currently available evidence should be presented to patients in order to select the most appropriate option for the individual.

Using queuing theory to analyse the government's 4-H completion time target in accident and emergency departments.

This paper uses a queuing model to evaluate completion times in Accident and Emergency (A&E) departments in the light of the Government target of completing and discharging 98% of patients inside 4 h. It illustrates how flows though an A&E can be accurately represented as a queuing process, how outputs can be used to visualise and interpret the 4-h Government target in a simple way and how the model can be used to assess the practical achievability of A&E targets in the future. The paper finds that A&E targets have resulted in significant improvements in completion times and thus deal with a major source of complaint by users of the National Health Service in the U.K. It suggests that whilst some of this improvement is attributable to better management, some is also due to the way some patients in A&E are designated and therefore counted through the system. It finds for example that the current target would not have been possible without some form of patient re-designation or re-labelling taking place. Further it finds that the current target is so demanding that the integrity of reported performance is open to question. Related incentives and demand management issues resulting from the target are also briefly discussed.

Clinical-outcome-based demand management in health services.

THE PROBLEM OF MANAGING DEMAND: Most healthcare systems have 'third-party payers' who face the problem of keeping within budgets despite pressures to increase resources due to the ageing population, new technologies and patient demands to lower thresholds for care. This paper uses the UK National Health Service as a case study to suggest techniques for system-based demand management, which aims to control demand and costs whilst maintaining the cost-effectiveness of the system. TECHNIQUE FOR MANAGING DEMAND: The technique for managing demand in primary, elective and urgent care consists of managing treatment thresholds for appropriate care, using a whole-systems approach and costing the care elements in the system. It is important to analyse activity in relation to capacity and demand. Examples of using these techniques in practice are given. CONCLUSION: The practical effects of using such techniques need evaluation. If these techniques are not used, managing demand and limiting healthcare expenditure will be at the expense of clinical outcomes and unmet need, which will perpetuate financial crises.

Autistic behavior in young boys with fragile X syndrome.

A sample of 57 boys with fragile X syndrome (fraX) between the ages of 24 and 133 months was rated using the Childhood Autism Rating Scale (CARS) to assess the extent to which autism and autistic features were evident in a young population. Fourteen subjects (approximately 25% of the sample) scored above the cutoff for autism, suggesting a relatively high incidence of autistic behavior. All but 2 of these 14 were in the mildly or moderately autistic range, however, and only a few items received severe ratings, suggesting that severe autism is relatively rare in fraX, at least during the early years. The CARS resulted in a continuum of autistic ratings in the fraX population, but no particular items on the CARS contributed disproportionately to autism ratings. A visual comparison of ratings on an autistic, non-fraX sample revealed similar profiles of ratings, suggesting that differentiating fraX and autism on the basis of CARS ratings is not likely. Within the fraX group, chronological age and socioeconomic status did not correlate with CARS ratings, but severity of delay was strongly related, such that more severely delayed children scored higher (more autistic) on the CARS.