Identification of last interglacial deposits in eastern Beringia: a cautionary note from the Palisades, interior Alaska

Last interglacial sediments in unglaciated Alaska and Yukon (eastern Beringia) are commonly identified by palaeoecological indicators and stratigraphic position ~2-5m above the regionally prominent Old Crow tephra (124±10ka). We demonstrate that this approach can yield erroneous age assignments using data from a new exposure at the Palisades, a site in interior Alaska with numerous exposures of last interglacial sediments. Tephrochronology, stratigraphy, plant macrofossils, pollen and fossil insects from a prominent wood-rich organic silt unit are all consistent with a last interglacial age assignment. However, six 14C dates on plant and insect macrofossils from the organic silt range from non-finite to 4.0 14C ka BP, indicating that the organic silt instead represents a Holocene deposit with a mixed-age assemblage of organic material. In contrast, wood samples from presumed last interglacial organic-rich sediments elsewhere at the Palisades, in a similar stratigraphic position with respect to Old Crow tephra, yield non-finite 14C ages. Given that local permafrost thaw since the last interglaciation may facilitate reworking of older sediments into new stratigraphic positions, minimum constraining ages based on 14C dating or other methods should supplement age assignments for last interglacial sediments in eastern Beringia that are based on palaeoecology and stratigraphic association with Old Crow tephra.

BRCA1 Immunohistochemical Staining as a Prognostic Indicator in Uterine Serous Carcinoma

OBJECTIVES: The objective of this study was to investigate the relationship between BRCA1 protein expression, as determined by immunohistochemistry, and clinical outcome in uterine serous carcinoma (USC). METHODS: A tissue microarray containing duplicate cores of 73 cases of USC was immunohistochemically stained with mouse anti-BRCA1 (Ab-1) mouse monoclonal (MS110) antibody. The cores were scored in a semiquantitative manner evaluating both the distribution and intensity of nuclear staining. BRCA1 protein expression was correlated with progression-free survival. RESULTS: Seventy-two of 73 cases were assessable, and there was a statistically significant decreased progression-free survival for those cases exhibiting tumor cell nuclei staining of 76% or greater (P = 0.0023). CONCLUSIONS: Our study illustrates that a low level of BRCA1 protein expression is a favorable prognostic indicator in USC, similar to what is observed in high-grade serous ovarian carcinoma. Further studies should focus on the BRCA1 status of USCs at a molecular level and also investigate whether BRCA1 protein expression is associated with response to chemotherapy in USC.

Clinicopathological features of homologous recombination-deficient epithelial ovarian cancers: Sensitivity to PARP inhibitors, platinum, and survival

Up to 50% of epithelial ovarian cancers (EOC) display defects in the homologous recombination (HR) pathway. We sought to determine the ramifications of the homologous recombination-deficient (HRD) status on the clinicopathologic features, chemotherapy response, and survival outcomes of patients with EOCs. HR status was determined in primary cultures from ascitic fluid in 50 chemotherapy-naïve patients by a functional RAD51 immunofluorescence assay and correlated with in vitro sensitivity to the PARP inhibitor (PARPi), rucaparib. All patients went on to receive platinum-based chemotherapy; platinum sensitivity, tumor progression, and overall survival were compared prospectively in HR-competent versus HRD patients. Compared with HR-competent patients, the HRD group was predominantly serous with a higher median CA125 at presentation. HRD was associated with higher ex vivo PARPi sensitivity and clinical platinum sensitivity. Median follow-up duration was 14 months; patients in the HRD group had lower tumor progression rates at 6 months, lower overall/disease-specific death rates at 12 months, and higher median survival. We therefore suggest that HRD as predicted by a functional RAD51 assay correlates with in vitro PARPi sensitivity, clinical platinum sensitivity, and improved survival outcome.

Psychosocial and academic characteristics of extremely low birth weight (<or =800 g) adolescents who are free of major impairment compared with term-born control subjects

To compare academic and cognitive ability, attention, attitudes, and behavior of extremely low birth weight (ELBW) adolescents who are free of major impairments at 17 years of age with term-born control subjects.

Children's judgements about pain at age 8-10 years:do extremely low birthweight (<or = 1000 g) children differ from full birthweight peers?

Children's judgements about pain at age 8-10 years were examined comparing two groups of children who had experienced different exposure to nociceptive procedures in the neonatal period: extremely low birthweight (ELBW) <or = 1000 g (N = 47) and full birthweight (FBW) > or = 2500 g (N = 37). The 24 pictures that comprise the Pediatric Pain Inventory, depicting events in four settings: medical, recreational, daily living, and psychosocial, were used as the pain stimuli. The subjects rated pain intensity using the Color Analog Scale and pain affect using the Facial Affective Scale. Child IQ and maternal education were statistically adjusted in group comparisons. Pain intensity and pain affect related to activities of daily living and recreation were significantly higher than psychosocial and medically related pain on both scales in both groups of children. Although the two groups of children did not differ overall in their perceptions of pain intensity or affect, the ELBW children rated medical pain intensity significantly higher than psychosocial pain, unlike the FBW group. Also, duration of neonatal intensive care unit stay for the ELBW children was related to increased pain affect ratings in recreational and daily living settings. Despite altered response to pain in the early years reported by parents, on the whole at 8-10 years of age ELBW children judged pain in pictures similarly to their term peers. However, differences were evident, which suggests that studies are needed of biobehavioural reactivity to pain beyond infancy, as well as research into beliefs, attitudes, and perceptions about pain during the course of childhood in formerly ELBW children.

Extremely premature (<or = 800 g) schoolchildren:multiple areas of hidden disability

To examine the functional abilities of extremely low birthweight (ELBW, <or = 800 g) children at school age compared with full term children.

Language development at 3 years in pre-term children of birth weight below 1000 g

Language development at 3 years of pre-term children born below 1000 g birth weight was compared with full-term controls matched for social background. The pre-term group used less complex expressive language and showed lower receptive understanding, auditory memory and verbal reasoning. Language outcome was related to intraventricular haemorrhage but not to global indication of postnatal illness such as number of days on the ventilator. Average verbal intelligence in environmentally low risk, extremely low birth weight children is an insufficient indicator of complex language functioning.

Titanic Reflections

Five short prose pieces originally performed as interludes in Philip Hammond's Requiem for the Lost Souls of the Titanic, April 2012