Artificial intelligence for predictive biomarker discovery in immuno-oncology: a systematic review.

BACKGROUND: The widespread use of immune checkpoint inhibitors (ICIs) has revolutionised treatment of multiple cancer types. However, selecting patients who may benefit from ICI remains challenging. Artificial intelligence (AI) approaches allow exploitation of high-dimension oncological data in research and development of precision immuno-oncology. MATERIALS AND METHODS: We conducted a systematic literature review of peer-reviewed original articles studying the ICI efficacy prediction in cancer patients across five data modalities: genomics (including genomics, transcriptomics, and epigenomics), radiomics, digital pathology (pathomics), and real-world and multimodality data. RESULTS: A total of 90 studies were included in this systematic review, with 80% published in 2021-2022. Among them, 37 studies included genomic, 20 radiomic, 8 pathomic, 20 real-world, and 5 multimodal data. Standard machine learning (ML) methods were used in 72% of studies, deep learning (DL) methods in 22%, and both in 6%. The most frequently studied cancer type was non-small-cell lung cancer (36%), followed by melanoma (16%), while 25% included pan-cancer studies. No prospective study design incorporated AI-based methodologies from the outset; rather, all implemented AI as a post hoc analysis. Novel biomarkers for ICI in radiomics and pathomics were identified using AI approaches, and molecular biomarkers have expanded past genomics into transcriptomics and epigenomics. Finally, complex algorithms and new types of AI-based markers, such as meta-biomarkers, are emerging by integrating multimodal/multi-omics data. CONCLUSION: AI-based methods have expanded the horizon for biomarker discovery, demonstrating the power of integrating multimodal data from existing datasets to discover new meta-biomarkers. While most of the included studies showed promise for AI-based prediction of benefit from immunotherapy, none provided high-level evidence for immediate practice change. A priori planned prospective trial designs are needed to cover all lifecycle steps of these software biomarkers, from development and validation to integration into clinical practice.

Precision of the GE Lunar Total Body-Less Head Scan for the Measurement of Three-Compartment Body Composition in Athletes.

INTRODUCTION: Dual energy X-ray absorptiometry (DXA) is widely used for the assessment of lean mass (LM), fat mass (FM) and bone mineral content (BMC). When observing standardised protocols, DXA has a high level of precision for the assessment of total body composition, including the head region. However, including the head region may have limited relevance in athletes and can be problematic when positioning taller athletes who exceed scan boundaries. This study investigated the precision of a new total-body-less-head (TBLH) DXA scan for three-compartment body composition measurement in athletes, with outcomes compared to the standard total-body DXA scan. METHODS: Precision errors were calculated from two consecutive scans with re-positioning (Lunar iDXA, GE Healthcare, Madison, WI), in male and female athletes from a range of sports. TBLH precision was determined from repeat scans in 95 athletes (male n = 55; female n = 40; age: 26.0 ± 8.5 y; body mass: 81.2 ± 20.5 kg; stature: 1.77 ± 0.11 m), and standard total-body scan precision was derived from a sub-sample of 58 athletes (male n = 19; female n = 39; age: 27.6 ± 9.9 y; body mass: 69.6 ± 14.8 kg; stature: 1.72 ± 0.94 m). Data from the sub-sample were also used to compare precision error and 3-compartment body composition outcomes between the standard total-body scan and the TBLH scan. RESULTS: TBLH precision errors [root mean squared-standard deviation, RMS-SD (coefficient of variation, %CV)] were bone mineral content (BMC): 15.6 g (0.5%), lean mass (LM): 254.3 g (0.4%) and fat mass (FM): 199.4 g (1.3%). These outcomes compared favourably to the precision errors derived from the standard total-body scan [BMC: 12.4 g (0.4%), LM: 202.2 g (0.4%), and FM: 160.8 g (1.1%)]. The TBLH scan resulted in lower BMC (-19.5%), LM (-6.6%), and FM (-4.5%) compared to the total-body scan (BMC: 2,308 vs. 2,865 g; LM: 46,954 vs. 50,276 g; FM: 15,183 vs. 15,888 g, all p<0.005). ConclusionThe TBLH scan demonstrates high in-vivo precision comparable to that of the standard total-body scan in a heterogeneous cohort of athletes. Given the impact of head exclusion on total body composition outcomes, TBLH scans should not be used interchangeably with the standard total-body scan.

Development of a mapping function ("crosswalk") for the conversion of scores between the Oswestry Disability Index (ODI) and the Core Outcome Measures Index (COMI).

INTRODUCTION: The Oswestry Disability Index (ODI) and the Core Outcome Measures Index (COMI) are two commonly used self-rating outcome instruments in patients with lumbar spinal disorders. No formal crosswalk between them exists that would otherwise allow the scores of one to be interpreted in terms of the other. We aimed to create such a mapping function. METHODS: We performed a secondary analysis of ODI and COMI data previously collected from 3324 patients (57 ± 17y; 60.3% female) at baseline and 1y after surgical or conservative treatment. Correlations between scores and Cohen's kappa for agreement (κ) regarding achievement of the minimal clinically important change (MCIC) score on each instrument (ODI, 12.8 points; COMI, 2.2 points) were calculated, and regression models were built. The latter were tested for accuracy in an independent set of registry data from 634 patients (60 ± 15y; 56.8% female). RESULTS: All pairs of measures were significantly positively correlated (baseline, 0.73; 1y follow-up (FU), 0.84; change-scores, 0.73). MCIC for COMI was achieved in 53.9% patients and for ODI, in 52.4%, with 78% agreement on an individual basis (κ = 0.56). Standard errors for the regression slopes and intercepts were low, indicating excellent prediction at the group level, but root mean square residuals (reflecting individual error) were relatively high. ODI was predicted as COMI × 7.13-4.20 (at baseline), COMI × 6.34 + 2.67 (at FU) and COMI × 5.18 + 1.92 (for change-score); COMI was predicted as ODI × 0.075 + 3.64 (baseline), ODI × 0.113 + 0.96 (FU), and ODI × 0.102 + 1.10 (change-score). ICCs were 0.63-0.87 for derived versus actual scores. CONCLUSION: Predictions at the group level were very good and met standards justifying the pooling of data. However, we caution against using individual values for treatment decisions, e.g. attempting to monitor patients over time, first with one instrument and then with the other, due to the lower statistical precision at the individual level. The ability to convert scores via the developed mapping function should open up more centres/registries for collaboration and facilitate the combining of data in meta-analyses.

Breaking free from thermodynamic constraints: thermal acclimation and metabolic compensation in a freshwater zooplankton species.

Respiration rates of ectothermic organisms are affected by environmental temperatures, and sustainable metabolism at high temperatures sometimes limits heat tolerance. Organisms are hypothesized to exhibit acclimatory metabolic compensation effects, decelerating their metabolic processes below Arrhenius expectations based on temperature alone. We tested the hypothesis that either heritable or plastic heat tolerance differences can be explained by metabolic compensation in the eurythermal freshwater zooplankton crustacean Daphnia magna We measured respiration rates in a ramp-up experiment over a range of assay temperatures (5-37°C) in eight genotypes of D. magna representing a range of previously reported acute heat tolerances and, at a narrower range of temperatures (10-35°C), in D. magna with different acclimation history (either 10 or 25°C). We discovered no difference in temperature-specific respiration rates between heat-tolerant and heat-sensitive genotypes. In contrast, we observed acclimation-specific compensatory differences in respiration rates at both extremes of the temperature range studied. Notably, there was a deceleration of oxygen consumption at higher temperature in 25°C-acclimated D. magna relative to their 10°C-acclimated counterparts, observed in active animals, a pattern corroborated by similar changes in filtering rate and, partly, by changes in mitochondrial membrane potential. A recovery experiment indicated that the reduction of respiration was not caused by irreversible damage during exposure to a sublethal temperature. Response time necessary to acquire the respiratory adjustment to high temperature was lower than for low temperature, indicating that metabolic compensation at lower temperatures requires slower, possibly structural changes.

Topical Review: Perceptual-cognitive Skills, Methods, and Skill-based Comparisons in Interceptive Sports.

SIGNIFICANCE: We give a comprehensive picture of perceptual-cognitive (PC) skills that could contribute to performance in interceptive sports. Both visual skills that are low level and unlikely influenced by experience and higher-level cognitive-attentional skills are considered, informing practitioners for identification and training and alerting researchers to gaps in the literature.Perceptual-cognitive skills and abilities are keys to success in interceptive sports. The interest in identifying which skills and abilities underpin success and hence should be selected and developed is likely going to grow as technologies for skill testing and training continue to advance. Many different methods and measures have been applied to the study of PC skills in the research laboratory and in the field, and research findings across studies have often been inconsistent. In this article, we provide definitional clarity regarding whether a skill is primarily visual attentional (ranging from fundamental/low-level skills to high-level skills) or cognitive. We review those skills that have been studied using sport-specific stimuli or tests, such as postural cue anticipation in baseball, as well as those that are mostly devoid of sport context, considered general skills, such as dynamic visual acuity. In addition to detailing the PC skills and associated methods, we provide an accompanying table of published research since 1995, highlighting studies (for various skills and sports) that have and have not differentiated across skill groups.

Does geographic variation in thermal tolerance in Daphnia represent trade-offs or conditional neutrality?

Geographic variation in thermal tolerance in Daphnia seems to represent genetic load at the loci specifically responsible for heat tolerance resulting from conditional neutrality. We see no evidence of trade-offs between fitness-related traits at 25 °C vs. 10 °C or between two algal diets across Daphnia magna clones from a variety of locations representing the opposite ends of the distribution of long-term heat tolerance. Likewise, we found no evidence of within-environment trade-offs between heat tolerance and fitness-related traits in any of the environments. Neither short-term and long-term heat tolerance shows any consistent relationship with lipid fluorescence polarization and lipid peroxidation across clones or environments. Pervasive positive correlations between fitness-related traits indicate differences in genetic load rather than trade-off based local adaptation or thermal specialization. For heat tolerance such differences may be caused by either relaxation of stabilizing selection due to lower exposure to high temperature extremes, i.e., conditional neutrality, or by small effective population size followed by the recent range expansion.

Organizational uptake of NICE guidance in promoting employees' psychological health.

BACKGROUND: Annual costs to organizations of poor mental health are estimated to be between £33 billion and £42 billion. The UK's National Institute for Clinical Excellence (NICE) has produced evidence-based guidance on improving employees' psychological health, designed to encourage organizations to take preventative steps in tackling this high toll. However, the extent of implementation is not known outside the National Health Service. AIMS: To assess the awareness and implementation of NICE guidance on workplace psychological health. METHODS: A total of 163 organizations participated in a survey of UK-based private, public and third sector organizations employing an accumulated minimum of 322 033 workers. RESULTS: Seventy-seven per cent of organizations were aware of the NICE guidance for improving mental well-being in the workplace, but only 37% were familiar with its recommendations. Less than half were aware of systems in place for monitoring employees' mental well-being and only 12% confirmed that this NICE guidance had been implemented in their workplace. Where employee health and well-being featured as a regular board agenda item, awareness and implementation of NICE guidance were more likely. Significant associations were found between organizational sector and size and uptake of many specific features of NICE guidance. CONCLUSIONS: The majority of organizations are aware of NICE guidance in general, but there is a wide gap between this and possession of detailed knowledge and implementation. The role of sector and size of organization is relevant to uptake of some features of NICE guidance, although organizational leadership is important where raised awareness and implementation are concerned.

Children sustain high levels of skin DNA photodamage, with a modest increase of serum 25-hydroxyvitamin D3 , after a summer holiday in Northern Europe.

BACKGROUND: Childhood solar ultraviolet radiation (UVR) exposure increases the risk of skin cancer in adulthood, which is associated with mutations caused by UVR-induced cyclobutane pyrimidine dimers (CPD). Solar UVR is also the main source of vitamin D, essential for healthy bone development in children. OBJECTIVES: To assess the impact of a 12-day Baltic Sea (54° N) beach holiday on serum 25-hydroxyvitamin D3 [25(OH)D3 ] and CPD in 32 healthy Polish children (skin types I-IV). METHODS: Blood and urine were collected before and after the holiday and assessed for 25(OH)D3 and excreted CPD, respectively, and personal UVR exposure was measured. Diaries were used to record sunbathing, sunburn and sunscreen use. Before- and after-holiday skin redness and pigmentation were measured by reflectance spectroscopy. RESULTS: The average ± SD daily exposure UVR dose was 2·4 ± 1·5 standard erythema doses (SEDs), which is borderline erythemal. The mean concentration of 25(OH)D3 increased (× 1·24 ± 0·19) from 64·7 ± 13·3 to 79·3 ± 18·7 nmol L-1 (P < 0·001). Mean CPD increased 12·6 ± 10·0-fold from 26·9 ± 17·9 to 248·9 ± 113·4 fmol µmol-1 creatinine (P < 0·001). Increased 25(OH)D3 was accompanied by a very much greater increase in DNA damage associated with carcinogenic potential. Overall, skin type had no significant effects on behavioural, clinical or analytical outcomes, but skin types I/II had more CPD (unadjusted P = 0·0496) than skin types III/IV at the end of the holiday. CONCLUSIONS: Careful consideration must be given to the health outcomes of childhood solar exposure, and a much better understanding of the risk-benefit relationships of such exposure is required. Rigorous photoprotection is necessary for children, even in Northern Europe.

Empowering Lay-Counsellors with Technology: Masivukeni, a Standardized Multimedia Counselling Support Tool to Deliver ART Counselling.

Lay-counsellors in resource-limited settings convey critical HIV- and ART-information, and face challenges including limited training and variable application of counselling. This study explored lay-counsellors and Department of Health (DoH) perspectives on the utility of a multimedia adherence counselling program. Masivukeni, an mHealth application that provides scaffolding for delivering standardized ART counselling was used in a 3-year randomized control trail at two primary health care clinics in Cape Town, South Africa. In this programmatic and descriptive narrative report, we describe the application; lay-counsellors' response to open-ended questions regarding their experience with using Masivukeni; and perspectives of the City of Cape Town and Western Cape Government DoH, obtained through ongoing engagements and feedback sessions. Counsellors reported Masivukeni empowered them to provide high quality counselling. DoH indicated strong support for a future implementation study assessing feasibility for larger scale roll-out. Masivukeni has potential as a counselling tool in resource-limited settings.

Children's everyday exposure to food marketing: an objective analysis using wearable cameras.

BACKGROUND: Over the past three decades the global prevalence of childhood overweight and obesity has increased by 47%. Marketing of energy-dense nutrient-poor foods and beverages contributes to this worldwide increase. Previous research on food marketing to children largely uses self-report, reporting by parents, or third-party observation of children's environments, with the focus mostly on single settings and/or media. This paper reports on innovative research, Kids'Cam, in which children wore cameras to examine the frequency and nature of everyday exposure to food marketing across multiple media and settings. METHODS: Kids'Cam was a cross-sectional study of 168 children (mean age 12.6 years, SD = 0.5) in Wellington, New Zealand. Each child wore a wearable camera on four consecutive days, capturing images automatically every seven seconds. Images were manually coded as either recommended (core) or not recommended (non-core) to be marketed to children by setting, marketing medium, and product category. Images in convenience stores and supermarkets were excluded as marketing examples were considered too numerous to count. RESULTS: On average, children were exposed to non-core food marketing 27.3 times a day (95% CI 24.8, 30.1) across all settings. This was more than twice their average exposure to core food marketing (12.3 per day, 95% CI 8.7, 17.4). Most non-core exposures occurred at home (33%), in public spaces (30%) and at school (19%). Food packaging was the predominant marketing medium (74% and 64% for core and non-core foods) followed by signs (21% and 28% for core and non-core). Sugary drinks, fast food, confectionary and snack foods were the most commonly encountered non-core foods marketed. Rates were calculated using Poisson regression. CONCLUSIONS: Children in this study were frequently exposed, across multiple settings, to marketing of non-core foods not recommended to be marketed to children. The study provides further evidence of the need for urgent action to reduce children's exposure to marketing of unhealthy foods, and suggests the settings and media in which to act. Such action is necessary if the Commission on Ending Childhood Obesity's vision is to be achieved.

Changes in soil organic carbon fractions after remediation of a coastal floodplain soil.

Coastal floodplain soils and wetland sediments can store large amounts of soil organic carbon (SOC). These environments are also commonly underlain by sulfidic sediments which can oxidise to form coastal acid sulfate soils (CASS) and contain high concentrations of acidity and trace metals. CASS are found on every continent globally except Antarctica. When sulfidic sediments are oxidised, scalds can form, which are large bare patches without vegetation. However, SOC stocks and fractions have not been quantified in these coastal floodplain environments. We studied the changes in soil geochemistry and SOC stocks and fractions three years after remediation of a CASS scald. Remediation treatments included raising water levels, and addition of either lime (LO) or lime and mulch (LM) relative to a control (C) site. We found SOC concentrations in the remediated sites (LO and LM) were more than double than that found at site C, reflected in the higher SOC stocks to a depth of 1.6 m (426 Mg C/ha, 478 Mg C/ha and 473 Mg C/ha at sites C, LO and LM, respectively). The particulate organic C (POC) fraction was higher at sites LO and LM due to increased vegetation and biomass inputs, compared to site C. Reformation of acid volatile sulfide (AVS) occurred throughout the profile at site LM, whereas only limited AVS reformation occurred at sites LO and C. Higher AVS at site LM may be linked to the additional source of organic matter provided by the mulch. POC can also potentially contribute to decreasing acidity as a labile SOC source for Fe(3+) and SO4(2-) reduction. Therefore, coastal floodplains and wetlands are a large store of SOC and can potentially increase SOC following remediation due to i) reduced decomposition rates with higher water levels and waterlogging, and ii) high C inputs due to rapid revegetation of scalded areas and high rates of biomass production. These results highlight the importance of maintaining vegetation cover in coastal floodplains and wetlands for sequestering SOC.

Recording occupation in general practice--a second cycle audit.

BACKGROUND: An audit of working age patients' records in two Cornish general practices in 2012 found infrequent and inconsistent recording of patients' occupations. A concurrent survey of general practitioners (GPs) in Cornwall found that a majority of them believed it was important to do so. AIMS: To review occupation recording in the same practices a year later and to audit a third practice, following the introduction of the electronic fit note. To repeat the survey of attitudes to recording occupation in GPs in Cornwall. METHODS: We manually checked 300 randomly selected patient records in Practice A and electronically searched all records of working age patients (aged 16-65 years) in Practices B and C for recorded occupation. We sent an electronic survey of attitudes to recording occupation to 202 GPs in Cornwall. RESULTS: Recording of occupation increased from 17 to 30% of records (χ(2) = 15, P < 0.001) in Practice A and from 12 to 14% (χ(2) = 16.5, P < 0.001) in Practice B. In Practice C, 1% of records had occupation recorded and coded. The proportion of GPs in Cornwall who said that it is important to records patients' occupation increased from 70 to 90% (Fisher's exact statistic 0.01, P < 0.05). CONCLUSIONS: Recording of patients' occupation increased in both practices from 2012 to 2013, but remains infrequent and inconsistent and the very low levels in a third practice not previously audited is of concern.

Is access to alcohol associated with alcohol/substance abuse among people diagnosed with anxiety/mood disorder?

OBJECTIVES: To investigate the relationship between access to off-license alcohol outlets and areas with dual treatment for alcohol/drug abuse and anxiety/mood disorder compared to areas with anxiety/mood disorder only in an urban setting in New Zealand. STUDY DESIGN: Ecologic study. METHODS: Within small areas (2840 meshblocks, mean size 0.05 km(2)) in the city of Auckland, New Zealand, counts of adults receiving anxiety/mood disorder treatment (2008-9) were identified and the proportions of these individuals also receiving treatment for alcohol/drug abuse were generated. Access to off-license alcohol outlets were defined as: 1) shortest road distance from the population-weighted centroid of each small area to an outlet; 2) count of outlets within a 3 km road network buffer; and 3) relative density of outlets across Auckland (determined through kernel density estimates). To test for the relationship between access to alcohol outlets and dual diagnosis, meshblocks without any cases of anxiety/mood disorder were excluded from analyses. Remaining meshblocks were dichotomized into any or no dual diagnosis. Logistic regression was used to estimate the association between access to alcohol outlets and treatment for the dual conditions. RESULTS: Neighbourhoods with dual diagnosis were generally similar to those with anxiety/mood disorder only, in terms of ethnic and gender/age composition. Regression analyses indicated statistically significant decreased risk of dual diagnosis for those areas with the lowest density (using a buffer) of alcohol outlets (OR = 0.75, P-value = 0.027) compared with areas with the highest density, after adjustment for deprivation and population density. All access measures also indicated significant linear trends where dual diagnosis was more likely in areas with greater access. CONCLUSIONS: Generally, decreased access to alcohol outlets was associated with decreased odds of dual diagnosis of alcohol/drug abuse and anxiety/mood disorder. Measures to control access to alcohol outlets may be an important area for alcohol/substance abuse intervention, particularly for vulnerable sub-populations.

Oxidation of graphene 'bow tie' nanofuses for permanent, write-once-read-many data storage devices.

We have fabricated nanoscale fuses from CVD graphene sheets with a 'bow tie' geometry for write-once-read-many data storage applications. The fuses are programmed using thermal oxidation driven by Joule heating. Fuses that were 250 nm wide with 2.5 µm between contact pads were programmed with average voltages and powers of 4.9 V and 2.1 mW, respectively. The required voltages and powers decrease with decreasing fuse sizes. Graphene shows extreme chemical and electronic stability; fuses require temperatures of about 400 °C for oxidation, indicating that they are excellent candidates for permanent data storage. To further demonstrate this stability, fuses were subjected to applied biases in excess of typical read voltages; stable currents were observed when a voltage of 10 V was applied to the devices in the off state and 1 V in the on state for 90 h each.

An ecological study investigating the association between access to urban green space and mental health.

OBJECTIVES: This study aims to find whether proximity to urban green spaces is associated with human mental health. STUDY DESIGN: A cross-sectional examination of the relationship between access to urban green spaces and counts of anxiety/mood disorder treatments amongst residents (aged 15 years and over) in Auckland City, New Zealand. METHODS: Anxiety/mood disorder treatment counts by three age groups were aggregated to 3149 small area units in Auckland. Six measures of green space access were derived using GIS techniques involving total green spaces and useable green spaces. Negative binomial regression models have been fitted to test the relationship between access to green space and area-level anxiety/mood disorder treatment counts, adjusted for age and area-level deprivation. RESULTS: Anxiety/mood disorder treatment counts were associated with three green space measures. The proportion of both total and useable green space within 3 km and distance to nearest useable green space all indicated a protective effect of increased access to green space against anxiety/mood disorder treatment counts. Access to total and useable green space within 300 m did not exhibit significant associations. CONCLUSION: This study found that decreased distance to useable green space and increased proportion of green space within the larger neighbourhood were associated with decreased anxiety/mood disorder treatment counts in an urban environment. This suggests the benefits of green space on mental health may relate both to active participation in useable green spaces near to the home and observable green space in the neighbourhood environment.

Segmental chromosomal alterations have prognostic impact in neuroblastoma: a report from the INRG project.

BACKGROUND: In the INRG dataset, the hypothesis that any segmental chromosomal alteration might be of prognostic impact in neuroblastoma without MYCN amplification (MNA) was tested. METHODS: The presence of any segmental chromosomal alteration (chromosome 1p deletion, 11q deletion and/or chromosome 17q gain) defined a segmental genomic profile. Only tumours with a confirmed unaltered status for all three chromosome arms were considered as having no segmental chromosomal alterations. RESULTS: Among the 8800 patients in the INRG database, a genomic type could be attributed for 505 patients without MNA: 397 cases had a segmental genomic type, whereas 108 cases had an absence of any segmental alteration. A segmental genomic type was more frequent in patients >18 months and in stage 4 disease (P<0.0001). In univariate analysis, 11q deletion, 17q gain and a segmental genomic type were associated with a poorer event-free survival (EFS) (P<0.0001, P=0.0002 and P<0.0001, respectively). In multivariate analysis modelling EFS, the parameters age, stage and a segmental genomic type were retained in the model, whereas the individual genetic markers were not (P<0.0001 and RR=2.56; P=0.0002 and RR=1.8; P=0.01 and RR=1.7, respectively). CONCLUSION: A segmental genomic profile, rather than the single genetic markers, adds prognostic information to the clinical markers age and stage in neuroblastoma patients without MNA, underlining the importance of pangenomic studies.

Anoxygenic photosynthesis modulated Proterozoic oxygen and sustained Earth's middle age.

Molecular oxygen (O(2)) began to accumulate in the atmosphere and surface ocean ca. 2,400 million years ago (Ma), but the persistent oxygenation of water masses throughout the oceans developed much later, perhaps beginning as recently as 580-550 Ma. For much of the intervening interval, moderately oxic surface waters lay above an oxygen minimum zone (OMZ) that tended toward euxinia (anoxic and sulfidic). Here we illustrate how contributions to primary production by anoxygenic photoautotrophs (including physiologically versatile cyanobacteria) influenced biogeochemical cycling during Earth's middle age, helping to perpetuate our planet's intermediate redox state by tempering O(2) production. Specifically, the ability to generate organic matter (OM) using sulfide as an electron donor enabled a positive biogeochemical feedback that sustained euxinia in the OMZ. On a geologic time scale, pyrite precipitation and burial governed a second feedback that moderated sulfide availability and water column oxygenation. Thus, we argue that the proportional contribution of anoxygenic photosynthesis to overall primary production would have influenced oceanic redox and the Proterozoic O(2) budget. Later Neoproterozoic collapse of widespread euxinia and a concomitant return to ferruginous (anoxic and Fe(2+) rich) subsurface waters set in motion Earth's transition from its prokaryote-dominated middle age, removing a physiological barrier to eukaryotic diversification (sulfide) and establishing, for the first time in Earth's history, complete dominance of oxygenic photosynthesis in the oceans. This paved the way for the further oxygenation of the oceans and atmosphere and, ultimately, the evolution of complex multicellular organisms.

The role of ultrasound in the assessment of post-operative complications following hip arthroplasty.

Hip arthroplasty is one of the most commonly performed orthopedic procedures. Clinicians can be faced with the diagnostic dilemma of the patient presenting with a painful hip following arthroplasty and satisfactory post-operative radiographs. Identifying the cause of symptoms can be challenging and ultrasound is increasingly being utilized in the evaluation of potential soft tissue complications following hip surgery. In this article, we describe the common surgical approaches used during hip arthroplasty as this can influence the nature and location of subsequent complications. A review of the literature is presented along with the imaging appearances frequently encountered when imaging this patient population.