Lack of intergenerational reproductive conflict, rather than lack of inclusive fitness benefits, explains absence of post-reproductive lifespan in long-finned pilot whales.

Life-history theory suggests that individuals should reproduce until death, yet females of a small number of mammals live for a significant period after ceasing reproduction, a phenomenon known as post-reproductive lifespan. It is thought that the evolution of this trait is facilitated by increasing local relatedness throughout a female's lifetime. This allows older females to gain inclusive fitness through helping their offspring (known as a mother effect) and/or grandoffspring (known as a grandmother effect), rather than gaining direct fitness through reproducing. However, older females may only benefit from stopping reproducing when their direct offspring compete with those of their daughters. Here, we investigate whether a lack of post-reproductive lifespan in long-finned pilot whales (Globicephala melas) results from minimal benefits incurred from the presence of older females, or from a lack of costs resulting from mother-daughter co-reproduction. Using microsatellite data, we conducted parentage analysis on individuals from 25 pods and find that younger females were more likely to have offspring if their mother was present in their pod, indicating that mothers may assist inexperienced daughters to reproduce. However, we found no evidence of reproductive conflict between co-reproducing mothers and daughters, indicating that females may be able to reproduce into old age while simultaneously aiding their daughters in reproduction. This highlights the importance of reproductive conflict in the evolution of a post-reproductive lifespan and demonstrates that mother and grandmother effects alone do not result in the evolution of a post-reproductive lifespan.

Diagnostic value of 68 Ga-DOTATATE PET-CT imaging for staging of ER+ /PR+ HER2- breast cancer patients with metastatic disease: Comparison with conventional imaging with bone scan, diagnostic CT and 18 F-FDG PET-CT in a prospective pilot trial.

INTRODUCTION: 18 F-Fludeoxyglucose PET-CT (FDG) is increasingly used to stage breast cancer. Most breast cancers express the Oestrogen Receptor (ER) and Progesterone Receptor (PR), and this subtype demonstrates lower activity on FDG imaging. Somatostatin receptors (SSTR) offer a potentially improved radiotracer target for ER+ /PR+ breast cancer. We present the first in vivo clinical study comparing 68 Ga-DOTATATE PET-CT (DOTA) to FDG and conventional imaging (bone scan and diagnostic CT), in metastatic ER+ /PR+ human epidermal growth factor receptor 2 (HER2) negative breast cancer. METHODS: Patients with clinically progressive metastatic ER+ /PR+ HER2- breast cancer underwent restaging with DOTA, FDG and conventional imaging. Scans were analysed visually, and semi-quantitatively. Wilcoxon-Rank Scoring was used to assess significance. RESULTS: Ten women (mean age 57 years) underwent imaging. 8/10 demonstrated disease on both DOTA and FDG. 2/10 positive on conventional imaging, but DOTA- /FDG- , and had no disease progression at 1-year follow-up. Heterogeneity of uptake was seen between DOTA and FDG with 5 bone lesions DOTA+ /FDG- and 1 bone lesion FDG+ /DOTA- . Twenty-one visceral lesions were FDG+ /DOTA- (2 patients), with 10/21 identified on conventional imaging. Maximum standard uptake values (SUV max) of DOTA were greater than FDG (10.9 vs. 6.6, P = ns). Four sites were biopsied (3 patients). 3/4 had high ER/PR expression (mean DOTA SUV max 9.4) and 1/4 low ER/PR expression (DOTA SUV max 3.1). CONCLUSION: Whilst we have not demonstrated DOTA to be superior to FDG in staging of ER+ /PR+ breast cancers, DOTA may have a role in assessing HR status and treatment decisions; further evaluation of this is warranted.

3-Year Freedom from Progression After 68Ga-PSMA PET/CT-Triaged Management in Men with Biochemical Recurrence After Radical Prostatectomy: Results of a Prospective Multicenter Trial.

68Ga-labeled prostate-specific membrane antigen (PSMA) PET/CT is increasingly used in men with biochemical recurrence (BCR) after radical prostatectomy (RP), but its longer-term prognostic or predictive potential in these men is unknown. The aim of this study was to evaluate the predictive value of PSMA PET for a 3-y freedom from progression (FFP) in men with BCR after RP undergoing salvage radiotherapy (sRT). Methods: This prospective multicenter study enrolled 260 men between 2015 and 2017. Eligible patients were referred for PSMA PET with a rising level of prostate-specific antigen (PSA) after RP. Management after PSMA PET was recorded but not mandated. PSMA PET protocols were standardized across sites and reported prospectively. Clinical, pathologic, and surgical information; sRT; timing and duration of androgen deprivation; 3-y PSA results; and clinical events were documented. FFP was defined as a PSA rise of no more than 0.2 ng/mL above nadir after sRT, with no additional treatment. Results: The median PSA was 0.26 ng/mL (interquartile range, 0.15-0.59 ng/mL), and follow-up was 38 mo (interquartile range, 31-43 mo). PSMA PET had negative results in 34.6% (90/260), showed disease confined to the prostatic fossa in 21.5% (56/260), showed disease in the pelvic nodes in 26.2% (68/260), and showed distant disease in 17.7% (46/260). Of the patients, 71.5% (186/260) received sRT: 38.2% (71/186) to the fossa only, 49.4% (92/186) to the fossa plus the pelvic nodes, and 12.4% (23/186) to the nodes alone or stereotactic body radiation therapy. PSMA PET was highly predictive of FFP at 3 y after sRT. Overall, FFP was achieved in 64.5% (120/186) of those who received sRT, 81% (81/100) with negative results or fossa-confined findings versus 45% (39/86) with extrafossa disease (P < 0.0001). On logistic regression, PSMA PET was more independently predictive of FFP than established clinical predictors, including PSA, T stage, surgical margin status, or Gleason score (P < 0.002). Thirty-two percent of men with a negative PSMA PET result did not receive treatment. Of these, 66% (19/29) progressed, with a mean rise in PSA of 1.59 ng/mL over the 3 y. Conclusion: PSMA PET results are highly predictive of FFP at 3 y in men undergoing sRT for BCR after RP. In particular, men with negative PSMA PET results or disease identified as still confined to the prostatic fossa demonstrate high FFP, despite receiving less extensive radiotherapy and lower rates of additional androgen deprivation therapy than those with extrafossa disease.

Is occipital bending a structural biomarker of risk for depression and sensitivity to treatment?

Occipital bending (OB) describes asymmetry of the occipital lobes where one lobe wraps across the midline, and has been associated with the presence of mood disorders. We evaluated the relationship between OB and major depressive disorder (MDD) in a large population of subjects from the International Study to Predict Optimized Treatment in Depression. MDD patients (n = 231) and healthy controls (n = 68) underwent MRI and neuropsychiatric evaluation, including response or remission to antidepressant medication at baseline and at 8 weeks. Cortical thickness, ventricular volumes and regional grey matter volumes were measured. OB was visually assessed and OB angle measured using a semi-automated method. Correlations with MDD diagnosis, MRI measures and clinical features were tested. Results demonstrated a greater proportion of rightwards OB in MDD compared to control subjects (p = 0.02). There was no difference in the total prevalence of OB (combined left and rightward bending) between MDD and controls. MDD subjects with right OB had greater cortical thickness in three medial occipital regions (cuneus, lingual gyrus and calcarine sulcus) on the left. Lateral ventricular size was 20% lower bilaterally in right OB MDD subjects compared to non-OB MDD subjects. OB was not associated with severity (HDRS-17). Our data suggest the presence of a strong link between greater rightward occipital bending and MDD. Rightward-OB is associated with greater left medial occipital cortical thickness, and with reduced lateral ventricular size. The cause for greater rightward bending in MDD patients is unclear, however our data suggest a developmental aetiology.