Response of the Great Barrier Reef to sea level and environmental changes over the past 30,000 years

Previous drilling through submerged fossil coral reefs has greatly improved our understanding of the general pattern of sea-level change since the Last Glacial Maximum, however, how reefs responded to these changes remains uncertain. Here we document the evolution of the Great Barrier Reef (GBR), the world\u27s largest reef system, to major, abrupt environmental changes over the past 30 thousand years based on comprehensive sedimentological, biological and geochronological records from fossil reef cores. We show that reefs migrated seaward as sea level fell to its lowest level during the most recent glaciation (~20.5-20.7 thousand years ago (ka)), then landward as the shelf flooded and ocean temperatures increased during the subsequent deglacial period (~20-10 ka). Growth was interrupted by five reef-death events caused by subaerial exposure or sea-level rise outpacing reef growth. Around 10 ka, the reef drowned as the sea level continued to rise, flooding more of the shelf and causing a higher sediment flux. The GBR\u27s capacity for rapid lateral migration at rates of 0.2-1.5 m yr−1 (and the ability to recruit locally) suggest that, as an ecosystem, the GBR has been more resilient to past sea-level and temperature fluctuations than previously thought, but it has been highly sensitive to increased sediment input over centennial-millennial timescales

Prognostic Breast Cancer Signature Identified from 3D Culture Model Accurately Predicts Clinical Outcome across Independent Datasets

One of the major tenets in breast cancer research is that early detection is vital for patient survival by increasing treatment options. To that end, we have previously used a novel unsupervised approach to identify a set of genes whose expression predicts prognosis of breast cancer patients. The predictive genes were selected in a well-defined three dimensional (3D) cell culture model of non-malignant human mammary epithelial cell morphogenesis as down-regulated during breast epithelial cell acinar formation and cell cycle arrest. Here we examine the ability of this gene signature (3D-signature) to predict prognosis in three independent breast cancer microarray datasets having 295, 286, and 118 samples, respectively. Our results show that the 3D-signature accurately predicts prognosis in three unrelated patient datasets. At 10 years, the probability of positive outcome was 52, 51, and 47 percent in the group with a poor-prognosis signature and 91, 75, and 71 percent in the group with a good-prognosis signature for the three datasets, respectively (Kaplan-Meier survival analysis, p<0.05). Hazard ratios for poor outcome were 5.5 (95% CI 3.0 to 12.2, p<0.0001), 2.4 (95% CI 1.6 to 3.6, p<0.0001) and 1.9 (95% CI 1.1 to 3.2, p = 0.016) and remained significant for the two larger datasets when corrected for estrogen receptor (ER) status. Hence the 3D-signature accurately predicts breast cancer outcome in both ER-positive and ER-negative tumors, though individual genes differed in their prognostic ability in the two subtypes. Genes that were prognostic in ER+ patients are AURKA, CEP55, RRM2, EPHA2, FGFBP1, and VRK1, while genes prognostic in ER patients include ACTB, FOXM1 and SERPINE2 (Kaplan-Meier p<0.05). Multivariable Cox regression analysis in the largest dataset showed that the 3D-signature was a strong independent factor in predicting breast cancer outcome. The 3D-signature accurately predicts breast cancer outcome across multiple datasets and holds prognostic value for both ER-positive and ER-negative breast cancer. The signature was selected using a novel biological approach and hence holds promise to represent the key biological processes of breast cancer

Prognostic markers in cancer: the evolution of evidence from single studies to meta-analysis, and beyond

In oncology, prognostic markers are clinical measures used to help elicit an individual patient's risk of a future outcome, such as recurrence of disease after primary treatment. They thus facilitate individual treatment choice and aid in patient counselling. Evidence-based results regarding prognostic markers are therefore very important to both clinicians and their patients. However, there is increasing awareness that prognostic marker studies have been neglected in the drive to improve medical research. Large protocol-driven, prospective studies are the ideal, with appropriate statistical analysis and clear, unbiased reporting of the methods used and the results obtained. Unfortunately, published prognostic studies rarely meet such standards, and systematic reviews and meta-analyses are often only able to draw attention to the paucity of good-quality evidence. We discuss how better-quality prognostic marker evidence can evolve over time from initial exploratory studies, to large protocol-driven primary studies, and then to meta-analysis or even beyond, to large prospectively planned pooled analyses and to the initiation of tumour banks. We highlight articles that facilitate each stage of this process, and that promote current guidelines aimed at improving the design, analysis, and reporting of prognostic marker research. We also outline why collaborative, multi-centre, and multi-disciplinary teams should be an essential part of future studies

Discovery and Preclinical Validation of Salivary Transcriptomic and Proteomic Biomarkers for the Non-Invasive Detection of Breast Cancer

A sensitive assay to identify biomarkers using non-invasively collected clinical specimens is ideal for breast cancer detection. While there are other studies showing disease biomarkers in saliva for breast cancer, our study tests the hypothesis that there are breast cancer discriminatory biomarkers in saliva using de novo discovery and validation approaches. This is the first study of this kind and no other study has engaged a de novo biomarker discovery approach in saliva for breast cancer detection. In this study, a case-control discovery and independent preclinical validations were conducted to evaluate the performance and translational utilities of salivary transcriptomic and proteomic biomarkers for breast cancer detection.Salivary transcriptomes and proteomes of 10 breast cancer patients and 10 matched controls were profiled using Affymetrix HG-U133-Plus-2.0 Array and two-dimensional difference gel electrophoresis (2D-DIGE), respectively. Preclinical validations were performed to evaluate the discovered biomarkers in an independent sample cohort of 30 breast cancer patients and 63 controls using RT-qPCR (transcriptomic biomarkers) and quantitative protein immunoblot (proteomic biomarkers). Transcriptomic and proteomic profiling revealed significant variations in salivary molecular biomarkers between breast cancer patients and matched controls. Eight mRNA biomarkers and one protein biomarker, which were not affected by the confounding factors, were pre-validated, yielding an accuracy of 92% (83% sensitive, 97% specific) on the preclinical validation sample set.Our findings support that transcriptomic and proteomic signatures in saliva can serve as biomarkers for the non-invasive detection of breast cancer. The salivary biomarkers possess discriminatory power for the detection of breast cancer, with high specificity and sensitivity, which paves the way for prediction model validation study followed by pivotal clinical validation

Data-independent proteomic screen identifies novel tamoxifen agonist that mediates drug resistance

A label-free quantitative variation of the recently developed data-independent shotgun proteomic method Precursor Acquisition Independent From Ion Count (PAcIFIC) was used to identify novel proteins implicated in cancer progression and resistance. Specifically, this screen identified the pro-metastatic protein anterior gradient 2 (AGR2) as significantly up-regulated in tamoxifen treated cells. Highlighting the need for direct proteome profiling methods like PAcIFIC, neither data-dependent gas-phase fractionation nor a transcriptomic screen detected AGR2 protein/transcript at significantly up-regulated levels. Further cell-based experiments using human cancer cell lines and in vivo xenografts confirmed the PAcIFIC hypothesis that AGR2 is up-regulated in MCF-7 cells post tamoxifen treatment, and that it is implicated in drug resistance mediation

Rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART): Study protocol for a randomized controlled trial

Background: Acute respiratory distress syndrome (ARDS) is associated with high in-hospital mortality. Alveolar recruitment followed by ventilation at optimal titrated PEEP may reduce ventilator-induced lung injury and improve oxygenation in patients with ARDS, but the effects on mortality and other clinical outcomes remain unknown. This article reports the rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART). Methods/Design: ART is a pragmatic, multicenter, randomized (concealed), controlled trial, which aims to determine if maximum stepwise alveolar recruitment associated with PEEP titration is able to increase 28-day survival in patients with ARDS compared to conventional treatment (ARDSNet strategy). We will enroll adult patients with ARDS of less than 72 h duration. The intervention group will receive an alveolar recruitment maneuver, with stepwise increases of PEEP achieving 45 cmH(2)O and peak pressure of 60 cmH2O, followed by ventilation with optimal PEEP titrated according to the static compliance of the respiratory system. In the control group, mechanical ventilation will follow a conventional protocol (ARDSNet). In both groups, we will use controlled volume mode with low tidal volumes (4 to 6 mL/kg of predicted body weight) and targeting plateau pressure <= 30 cmH2O. The primary outcome is 28-day survival, and the secondary outcomes are: length of ICU stay; length of hospital stay; pneumothorax requiring chest tube during first 7 days; barotrauma during first 7 days; mechanical ventilation-free days from days 1 to 28; ICU, in-hospital, and 6-month survival. ART is an event-guided trial planned to last until 520 events (deaths within 28 days) are observed. These events allow detection of a hazard ratio of 0.75, with 90% power and two-tailed type I error of 5%. All analysis will follow the intention-to-treat principle. Discussion: If the ART strategy with maximum recruitment and PEEP titration improves 28-day survival, this will represent a notable advance to the care of ARDS patients. Conversely, if the ART strategy is similar or inferior to the current evidence-based strategy (ARDSNet), this should also change current practice as many institutions routinely employ recruitment maneuvers and set PEEP levels according to some titration method.Hospital do Coracao (HCor) as part of the Program 'Hospitais de Excelencia a Servico do SUS (PROADI-SUS)'Brazilian Ministry of Healt

Características morfológicas de los pulmones de pollos de engorde normales y ascíticos y su posible correlación con otros parámetros morfofisiológicos

Con el objeto de establecer si existen diferencias entre pollos normales (sin ascitis) y pollos con ascitis hipóxica, mediante lacuantificación de algunas constantes fisiológicas, así como la caracterización de parámetros morfológicos pulmonares, se realizó un estudio clínico patológico en un grupo de 50.000 pollos de engorde de la raza Arbor Acres durante todo el ciclo productivo (42 días).Los valores de hematocrito y hemoglobina fueron siempre mayores en el grupo de animales ascíticos en comparación con lossanos de la misma edad (p). El volumen pulmonar se incrementó en todos los grupos al aumentar la edad. Las aves sanastuvieron un mayor volumen pulmonar en comparación con las escíticas, pero sin diferencias estadísticamente significativas (p). En general los machos sanos (MS) presentaron mayores valores de peso corporal en comparación con los ascíticos (MA) de su misma edad (p). Las hembras sanas (HS) también presentaron mayores valores de peso corporal en comparación con las ascíticas (HA) de su misma edad.Los animales ascíticos presentaron un mayor valor de la relación volumen pulmonar/ peso corporal x 100 comparados con lossanos; el tamaño del pulmón expresado como porcentaje del peso corporal, disminuyó a medida que los pollos crecieron, yaque el volumen pulmonar aumenta pero no en igual relación que lo hace el peso corporal, como se pudo corroborar en el presente experimento, donde el volumen pulmonar aumentó en una forma rápida hasta la 2a. edad (24-27 días) y a partir de ésta su crecimiento fue más lento. El índice cardíaco fue mayor en los animales ascíticos que en los sanos, independientemente de la edad y del sexo, con diferencias estadísticamente significativas (p).Los pollos sanos presentaron una mayor longitud del tibiotarso y del fémur que los ascíticos, así mismo los pollos sanos mostraron un mayor peso del fémur y del tibiotarso que los ascíticos. Se encontraron diferencias morfológicas entre los pulmones de pollos sanos comparados con los de pollos ascíticos, así: hemorragias en la luz de los parabronquios, aumento de la altura del epitelio de los parabronquios y del grosor de la musculatura de la entrada de los atrios, mayor cantidad de nódulos fibrosos, cartilaginosos-y mineralizados en animales con ascitis hipóxica

Diagnosis, treatment and beyond: Latina women’s psychological adjustment to breast cancer

Latina breast cancer survivors are not benefiting from advances in psychosocial interventions. Despite their greater breast cancer burden, there is a dearth of information about this population. This qualitative study examined the experiences of 18 immigrant Latina breast cancer survivors along the survivorship continuum, from diagnosis to long-term survivorship. The authors conducted separate focus groups with women in the acute, reentry, and long-term survivorship stages. Through grounded theory analysis, the authors uncovered 5 themes of experience: perceptions of psychological well-being, impact of diagnosis, impact of treatment, need for social support, and development of new attitudes. Some themes were applicable across all survivorship stages, whereas others were more salient at a particular stage. Within themes, the authors identified experiences reported in the general literature (i.e., the debilitating effect of chemotherapy) and distinct cultural experiences (i.e., fear that a cancer diagnosis leads to certain death). Results suggest that treatments tailored for each survivorship stage are more likely to be effective than generic interventions. These findings have the potential to lessen health disparities in utilization of psychosocial treatments by Latina breast cancer survivors

Paleoshorelines and lowstand sedimentation on subtropical shelves: a case study from the Fraser Shelf, Australia

Evidence of submerged paleoshorelines on tectonically stable continental shelves is represented by relict coastal depositional features that formed during periods of lower sea level. This study investigates two paleoshoreline features that extend 70 km from the Barwon Bank along the southeast Fraser Shelf, off eastern Australia. They are defined by well-lithified, mixed carbonate-siliciclastic deposits now at water depths of 60 m and between 80 and 100 m, located approximately 40 km seaward of the modern shoreline. High-resolution multibeam bathymetry data show geomorphic features that we interpret as paleodunes in the case of the 60 m feature, and paleobarriers in the case of the 80–100 m feature. Sub-bottom profiles also show evidence of prograded beach foresets and paleochannels as components of the Barwon Bank, which is a low and elongate bank that rises about 30 m above the surrounding shelf to a depth of 60 m. Carbonate cements in the rocks forming the paleoshoreline features reveal diagenetic influence of meteoric waters, suggesting that subaerial processes contributed to the formation and preservation of both features. Radiocarbon dating of bioclastic grains (coralline algae, benthic forams) yields an age range between 22.8 and 20.4 ka for the paleobarrier, and an age of 17.3 ka for the paleodune. The morphology of the submerged paleodunes is analogous to modern parabolic dunes on nearby Fraser and Moreton islands. The position and morphology of the paleodunes provide proxy information about the climate history of Australia during the late Quaternary, as these dunes are a likely consequence of the general continent-wide aridity during the Last Glacial Maximum. The preservation of the eolian dunes during marine transgression, despite their direct exposure to coastal hydrodynamic processes, suggests that the dunes were armoured, stabilised and lithified during the glacial lowstand, prior to drowning