Associations with other cancer-related biomarkers might contribute to poor outcomes in RAS-altered, younger patients with colorectal cancer.

Colorectal cancer (CRC) is a common cancer in younger adults. In patients undergoing liver resection with RAS-altered CRCs, there is evidence suggesting younger patients have worse outcomes than older patients. To explain this pattern, differences in associations between RAS status and other cancer-related biomarkers in tumors from younger versus older patients with CRC were evaluated in a cohort of 925 patients with CRC, 277 (30.0%) of whom were ≤50 years old, and 454 (49.1%) who had RAS-altered tumors. For 3 biomarkers, RNF43, APC, and microsatellite instability (MSI), the association with RAS status was significantly modified by age after adjustment for multiple testing. Specifically, younger patients with RAS-altered tumors were more likely to be MSI-high, RNF43 mutated, and APC wild type. These differences might contribute to the observed pattern of diminished survival in younger versus older patients with CRC with RAS-mutated tumors undergoing liver metastasis resection.

Multi-omic molecular profiling guide's efficacious treatment selection in refractory metastatic breast cancer: a prospective phase II clinical trial.

This prospective phase II clinical trial (Side Out 2) explored the clinical benefits of treatment selection informed by multi-omic molecular profiling (MoMP) in refractory metastatic breast cancers (MBCs). Core needle biopsies were collected from 32 patients with MBC at trial enrollment. Patients had received an average of 3.94 previous lines of treatment in the metastatic setting before enrollment in this study. Samples underwent MoMP, including exome sequencing, RNA sequencing (RNA-Seq), immunohistochemistry, and quantitative protein pathway activation mapping by Reverse Phase Protein Microarray (RPPA). Clinical benefit was assessed using the previously published growth modulation index (GMI) under the hypothesis that MoMP-selected therapy would warrant further investigation for GMI ≥ 1.3 in ≥ 35% of the patients. Of the 32 patients enrolled, 29 received treatment based on their MoMP and 25 met the follow-up criteria established by the trial protocol. Molecular information was delivered to the tumor board in a median time frame of 14 days (11-22 days), and targetable alterations for commercially available agents were found in 23/25 patients (92%). Of the 25 patients, 14 (56%) reached GMI ≥ 1.3. A high level of DNA topoisomerase I (TOPO1) led to the selection of irinotecan-based treatments in 48% (12/25) of the patients. A pooled analysis suggested clinical benefit in patients with high TOPO1 expression receiving irinotecan-based regimens (GMI ≥ 1.3 in 66.7% of cases). These results confirmed previous observations that MoMP increases the frequency of identifiable actionable alterations (92% of patients). The MoMP proposed allows the identification of biomarkers that are frequently expressed in MBCs and the evaluation of their role as predictors of response to commercially available agents. Lastly, this study confirmed the role of MoMP for informing treatment selection in refractory MBC patients: more than half of the enrolled patients reached a GMI ≥ 1.3 even after multiple lines of previous therapies for metastatic disease.

The impact of maternal birth month on reproductive performance: controlling for socio-demographic confounders.

Based on a 1900 census sample of 34,166 post-reproductive females (> or =45 years), the birth month effect was put to the test, for both lifetime fertility as well as child survival, controlling for maternal birth cohort (1826-1835, 1836-1845, 1846-1855), Duncan's SEI, urbanity, nativity, literacy and marital duration. Testing for potential cohort effects did not indicate a temporal trend in fertility by maternal birth month (seasonal Mann-Kendall test, p=0.578), while a minute increase in offspring survival was detected (p<0.001, Sen's estimator of slope=0.02, 95% CI=0.02 to 0.03). Further analyses of the maternal birth month effect on child survival were therefore seized. For lifetime fertility, ANOVA results indicated that maternal birth month was a major predictor for total offspring count (F11, 33606=1809.0, p<0.001), accounting for 37.2% of the total variability. In addition to main effects, a statistically significant interaction effect was observed (F538, 33606=2.2, p<0.001), with a corresponding effect size of eta2=0.40. Planned contrasts revealed that birth-month-specific differences in fertility achieved statistical significance (F11, 31798=1712.9, p<0.001), while post-hoc multiple comparisons for literacy and nativity displayed an inverse relationship with fertility, which meets demographic expectations. Controlling for all factors of interest, models of cohort-specific offspring counts (independent ANOVAs for 1826-1835: F157, 3467=26.3, p<0.001; 1836-1845: F182, 10299=75.5, p<0.001; 1846-1855: F199, 19859=137.9, p<0.001) indicated that women born in the first half of the year (particularly, January, February, April and May) achieved above-average parity, while those born in the latter half (namely, July, October, November and December) displayed markedly lower fertility averages. These monthly disparities are in line with previous observations and appear to be linked to seasonal optimal ripening of the oocyte or seasonal preovulatory over-ripeness ovopathy (Jongbloet, 1992).

Basics in paleodemography: a comparison of age indicators applied to the early medieval skeletal sample of Lauchheim.

Recent advances in the methods of skeletal age estimation have rekindled interest in their applicability to paleodemography. The current study contributes to the discussion by applying several long established as well as recently developed or refined aging methods to a subsample of 121 adult skeletons from the early medieval cemetery of Lauchheim. The skeletal remains were analyzed by 13 independent observers using a variety of aging techniques (complex method and other multimethod approaches, Transition Analysis, cranial suture closure, auricular surface method, osteon density method, tooth root translucency measurement, and tooth cementum annulation counting). The age ranges and mean age estimations were compared and results indicate that all methods showed smaller age ranges for the younger individuals, but broader age ranges for the older age groups.

Is perceived childlessness a cue for stereotyping? Evolutionary aspects of a social phenomenon.

The present research investigates the moderating role of the "child factor" in impression formation. 307 university students (148 males, 159 females) were asked to assess 14 traits related to physical attractiveness, resource accruing potential, and emotional stability. The stimulus person was either accompanied by a child or shown individually. As expected, targets depicted with children were believed to be more family-committed and to possess greater parenting skills. The child factor also favourably biased respondents' assessments in terms of honesty, faithfulness, and maturity. Women with children were assumed to be less ambitious, while men with children were believed to be more generous and possess higher status and financial security. All results are discussed within the greater evolutionary context of kin selection and the "good-parent process". It is hypothesized that the negative stereotyping of the voluntary childfree is a by-product of cues that infer prosocial behaviour--similar to those used in mate selection.

Does the sex of firstborn children influence subsequent fertility behavior? evidence from family reconstitution.

According to recent studies in evolutionary anthropology, firstborn daughters influence both parity progression and sibling survival by acting as so-called helpers at the nest. Based on 534 sets of household data from family reconstitution, the current analysis fails to show that offspring sex had any direct impact on maternal fertility, sibling survivorship, birth spacing, or reproductive span. Instead, the results indicate that fertility decisions were heavily affected by proximate factors such as child mortality and gender preferences. Families who had experienced child death were swift to substitute the loss with another pregnancy--a phenomenon known as replacement strategy. Similarly, a surplus of daughters acted as a strong impulse for parity progression, not because of potential helping effects but in an attempt to conceive additional sons. This is particularly apparent when the odds of grandmultiparity are considered.

Secondary sex ratio variation during stressful times: the impact of the French revolutionary wars on a German parish (1787-1802).

The observation that declines in the human secondary sex ratio (SSR) may be linked to stressful periconceptional periods has received considerable attention (Catalano [2003] Hum Reprod 18:1972-1975; Catalano et al. [2005] Int J Epidemiol 34:944-948, [2005] Hum Reprod 20:1221-1227, [2005] Paediatr Perinat Epidemiol 19:413-420). For the purpose of testing the external validity of this phenomenon, birth records from four German village genealogies (N = 1,048) were analyzed to study the impact of the French Revolutionary Wars (1787-1802) on the proportion of male births. All births were subdivided into three cohorts (prewar, 1787-1792; war, 1792-1797; and postwar, 1797-1802). Differences in SSR between cohorts achieved statistical significance (chi2= 7.695; df = 2; P = 0.021). In addition, changes in SSR before, during, and after the wars were monitored by risk analysis. Using the SSR of the prewar period as a control, the results of the war cohort failed to achieve statistical significance (regression coefficient, -0.257; ExpB= 0.773; P = 0.118), while the odds reduction of 32.3% in the postwar period proved to be statistically significant (regression coefficient, -0.390; ExpB= 0.677; P = 0.006). It is hypothesized that the experience of postwar economic hardship (attributable to lowered food availability paired with dietary changes) represents the most likely proximate cause. The study also finds evidence of a parental sex ratio manipulation strategy meant to offset the female-biased SSR after the wars. It is argued that from an evolutionary perspective both the decline in SSR in response to stress as well as parental manipulation of the tertiary sex ratio convey reproductive advantages.

Metric assessment of the "mastoid triangle" for sex determination: a validation study.

Recently, a metric approach to skeletal sex determination was published by Paiva and Segre which is based on the summation of two triangular areas defined by three distinct craniometric landmarks: Porion, Mastoidale, and Asterion. According to the authors, values for the total triangle > or =1447.40 mm(2) are characteristic for male crania, while values < or =1260.36 mm(2) are indicative of female skulls (95% confidence). In order to evaluate the method's validity, two sex- and age-documented samples of different provenience were analyzed (N=197). The results show that while the indicated measurements display significant sex differences, the technique is of little practical meaning where a single individual must be independently classified. It is hypothesized that differences in the expression of sexual dimorphism as well as a population-specific variability of the asterion location undermine the value of the mastoid triangle as a sex determinant.