Germline and somatic testing for ovarian Cancer: An SGO clinical practice statement.

Germline and somatic genetic testing have become critical components of care for people with ovarian cancer. The identification of germline and somatic pathogenic variants as well as homologous recombination deficiency can contribute to the prediction of treatment response, prognostic outcome, and suitability for targeted agents (e.g. poly (ADP-ribose) polymerase (PARP) inhibitors). Furthermore, identifying germline pathogenic variants can prompt cascade genetic testing for at-risk relatives. Despite the clinical benefits and consensus recommendations from several organizations calling for universal genetic testing in ovarian cancer, only about one third of patients complete germline or somatic genetic testing. The members of the Society of Gynecologic Oncology (SGO) Clinical Practice Committee have composed this statement to provide an overview of germline and somatic genetic testing for patients with epithelial ovarian cancer, focusing on available testing modalities and options for care delivery.

Morphology of nares associated with stereo-olfaction in baleen whales.

The sensory mechanisms used by baleen whales (Mysticeti) for locating ephemeral, dense prey patches in vast marine habitats are poorly understood. Baleen whales have a functional olfactory system with paired rather than single blowholes (nares), potentially enabling stereo-olfaction. Dimethyl sulfide (DMS) is an odorous gas emitted by phytoplankton in response to grazing by zooplankton. Some seabirds use DMS to locate prey, but this ability has not been demonstrated in whales. For 14 extant species of baleen whale, nares morphometrics (imagery from unoccupied aerial systems, UAS) was related to published trophic level indices using Bayesian phylogenetic mixed modelling. A significant negative relationship was found between nares width and whale trophic level (ß = -0.08, lower 95% CI = -0.13, upper 95% CI = -0.03), corresponding with a 39% increase in nares width from highest to lowest trophic level. Thus, species with nasal morphology best suited to stereo-olfaction are more zooplanktivorous. These findings provide evidence that some baleen whale species may be able to localize odorants e.g. DMS. Our results help direct future behavioural trials of olfaction in baleen whales, by highlighting the most appropriate species to study. This is a research priority, given the potential for DMS-mediated plastic ingestion by whales.

Humpback whales (Megaptera novaeangliae) attend both Mexico and Hawaii breeding grounds in the same winter: mixing in the northeast Pacific.

Humpback whales that assemble on winter breeding grounds in Mexico and Hawaii have been presumed to be, at least, seasonally isolated. Recently, these assemblies were declared Distinct Population Segments under the US Endangered Species Act. We report two humpback whales attending both breeding grounds in the same season-one moving from Hawaii to Mexico and the other from Mexico to Hawaii. The first was photo-identified in Maui, Hawaii on 23 February 2006 and again, after 53 days and 4545 km, on 17 April 2006 in the Revillagigedo Archipelago, Mexico. The second was photo-identified off Guerrero, Mexico on 16 February 2018 and again, 49 days and 5944 km later, on 6 April 2018 off Maui. The 2006 whale was identified in summer off Kodiak Island, Alaska; the 2018 whale off British Columbia. These Mexico-Hawaii identifications provide definitive evidence that whales in these two winter assemblies may mix during one winter season. This, combined with other lines of evidence on Mexico-Hawaii mixing, including interchange of individuals year to year, long-term similarity of everchanging songs, one earlier same-season travel record, and detection of humpback whales mid-ocean between these locations in winter, suggests reassessment of the 'distinctiveness' of these populations may be warranted.

Influence of Life-History Parameters on Persistent Organic Pollutant Concentrations in Blubber of Eastern North Pacific Gray Whales (Eschrichtius robustus).

Exposure to persistent organic pollutants (POPs) can significantly impact marine mammal health, reproduction, and fitness. This study addresses a significant 20-year gap in gray whale contaminant monitoring through analysis of POPs in 120 blubber biopsies. The scope of this substantial sample set is noteworthy in its range and diversity with collection between 2003 and 2017 along North America's west coast and across diverse sex, age, and reproductive parameters, including paired mothers and calves. Mean blubber concentrations of polychlorinated biphenyls (∑PCBs), dichlorodiphenyltrichloroethanes (∑DDTs), and chlordanes (∑CHLs) generally decreased since previous reports (1968-1999). This is the first report of polybrominated diphenyl ethers (PBDEs) and select hexachlorocyclohexanes (HCHs) in this species. Statistical modeling of the 19 most frequently detected compounds in this dataset revealed sex-, age-, and reproductive status-related patterns, predominantly attributed to maternal offloading. Mean POP concentrations differed significantly by sex in adults (17 compounds, up to 3-fold higher in males) but not in immatures (all 19 compounds). Mean POP concentrations were significantly greater in adults versus immatures in both males (17 compounds, up to 12-fold) and females (13 compounds, up to 3-fold). POP concentrations were detected with compound-specific patterns in nursing calves, confirming maternal offloading for the first time in this species.

Using anisotropic and narrowband ambient noise for continuous measurements of relative clock drift between independent acoustic recorders.

Relative clock drift between instruments can be an issue for coherent processing of acoustic signals, which requires data to be time-synchronized between channels. This work shows how cross correlation of anisotropic narrowband ambient noise allows continuous estimation of the relative clock drift between independent acoustic recorders, under the assumption that the spatial distribution of the coherent noise sources is stationary. This method is applied to two pairs of commercial passive acoustic recorders deployed up to 14 m apart at 6 and 12 m depth, respectively, over a period of 10 days. Occasional calibration signals show that this method allows time-synchronizing the instruments to within ±1 ms. In addition to a large linear clock drift component on the order of tens of milliseconds per hour, the results reveal for these instruments non-linear excursions of up to 50 ms that cannot be measured by standard methods but are crucial for coherent processing. The noise field displays the highest coherence between 50 and 100 Hz, a bandwidth dominated by what are believed to be croaker fish, which are particularly vocal in the evenings. Both the passive and continuous nature of this method provide advantages over time-synchronization using active sources.

OPTN/SRTR 2018 Annual Data Report: Pancreas.

The overall number of pancreas transplants continued to increase to 1027 in 2018, after a nadir of 947 in 2015. New additions to waiting list remained stable, with 1485 candidates added in 2018. Proportions of patients with type II diabetes waiting for transplant (14.6%) and undergoing transplant (14.8%) have steadily increased since 2016. Waiting times for simultaneous pancreas/kidney transplant have decreased; median months to transplant was 13.5 for simultaneous pancreas/kidney transplant and 19.7 for pancreas transplant alone in 2018. Outcomes, including patient and kidney survival, as well as rejection rates, have improved consistently over the past several years. Pancreas graft survival data are being collected by the Organ Procurement and Transplantation Network and will be included in a future report once there are sufficient cohorts for analysis.

OPTN/SRTR 2017 Annual Data Report: Pancreas.

In 2017, 1492 patients were added to the pancreas transplant waiting list, 964 listed as active, a slight increase from 2016. This is significant because for the first time in the past decade, the steady downward trend in additions to the waiting list has been reversed. Proportions of pancreas donors with cerebrovascular accident as cause of death decreased, with a concomitant increase in proportions with anoxia and head trauma. This is partly a result of the national opioid crisis, and it reflects increasing use of younger donors for pancreas transplant. The 2017 outcome report remains compromised by previous variation in reporting graft failure. Although the OPTN Pancreas Transplantation Committee has approved more precise definitions of pancreas graft failure, implementation of these definitions took place recently, and the data are not reflected in this report.

A whale of a tale: A One Environmental Health approach to study metal pollution in the Sea of Cortez.

Marine metal pollution is an emerging concern for human, animal, and ecosystem health. We considered metal pollution in the Sea of Cortez, which is a relatively isolated sea rich in biodiversity. Here there are potentially significant anthropogenic inputs of pollution from agriculture and metal mining. We considered the levels of 23 heavy metals and selenium in seven distinct cetacean species found in the area. Our efforts considered two different periods of time: 1999 and 2016/17. We considered the metal levels in relation to (1) all species together across years, (2) differences between suborders Odontoceti and Mysticeti, (3) each species individually across years, and (4) gender differences for each of these comparisons. We further compared metal levels found in sperm whale skin samples collected during these voyages to a previous voyage in 1999, to assess changes in metal levels over a longer timescale. The metals Mg, Fe, Al, and Zn were found at the highest concentrations across all species and all years. For sperm whales, we observed decreased metal levels from 1999 to 2016/2017, except for iron (Fe), nickel (Ni), and chromium (Cr), which either increased or did not change during this time period. These results indicate a recent change in the metal input to the Sea of Cortez, which may indicate a decreased concern for human, animal, and ecosystem health for some metals, but raises concern for the genotoxic metals Cr and Ni. This work was supported by NIEHS grant ES016893 (J.P.W.) and numerous donors to the Wise Laboratory.

Genetic data reveal mixed-stock aggregations of gray whales in the North Pacific Ocean.

Gray whales (Eschrichtius robustus) in the Western Pacific are critically endangered, whereas in the Eastern Pacific, they are relatively common. Holocene environmental changes and commercial whaling reduced their numbers, but gray whales in the Eastern Pacific now outnumber their Western counterparts by more than 100-fold. Herein, we investigate the genetic diversity and population structure within the species using a panel of genic single nucleotide polymorphisms. Results indicate the gray whale gene pool is differentiated into two substocks containing similar levels of genetic diversity, and that both our Eastern and Western geographical samples represent mixed-stock aggregations. Ongoing or future gene flow between the stocks may conserve genetic diversity overall, but admixture has implications for conservation of the critically endangered Western gray whale.

Humpback whale-generated ambient noise levels provide insight into singers' spatial densities.

Baleen whale vocal activity can be the dominant underwater ambient noise source for certain locations and seasons. Previous wind-driven ambient-noise formulations have been adjusted to model ambient noise levels generated by random distributions of singing humpback whales in ocean waveguides and have been combined to a single model. This theoretical model predicts that changes in ambient noise levels with respect to fractional changes in singer population (defined as the noise "sensitivity") are relatively unaffected by the source level distributions and song spectra of individual humpback whales (Megaptera novaeangliae). However, the noise "sensitivity" does depend on frequency and on how the singers' spatial density changes with population size. The theoretical model was tested by comparing visual line transect surveys with bottom-mounted passive acoustic data collected during the 2013 and 2014 humpback whale breeding seasons off Los Cabos, Mexico. A generalized linear model (GLM) estimated the noise "sensitivity" across multiple frequency bands. Comparing the GLM estimates with the theoretical predictions suggests that humpback whales tend to maintain relatively constant spacing between one another while singing, but that individual singers either slightly increase their source levels or song duration, or cluster more tightly as the singing population increases.

Lichen sclerosus Mistaken for Sexual Abuse--Prevention of Victimization.

This case report describes the forensic examination of 7 girls aged between 4-11 years with suspected sexual abuse. The children had been reported by local pediatricians, hospital physicians or authorities such as the youth welfare office and police due to mucosal changes in the anogenital area. All children presented with a clearly delimited, porcelain-like white discoloration of the skin in the anal and genital area with atrophic conversion to parchment-like skin. The markedly vulnerable skin exhibited very different manifestations of hemorrhagic dermal and mucosal defects in the area of the labia, the clitoris, the perineum and the perianal region. The hymen was intact in all cases. The skin changes are typical of lichen sclerosus et atrophicus, which is more common in prepubertal girls and post-menopausal women. Due to the chronic course, affected persons can develop sclerotic plaques, synechia of the labia minora and stenoses of the urinary tract and of the vaginal orifice, so that an early diagnosis is crucial. This condition is not infrequently taken by attending physicians as a sign of suspected sexual abuse, as the relevant findings are not recognized correctly. Furthermore, there are far-reaching consequences for the affected families, who are often faced with criminal prosecution, a breakdown of social familial structures and an enormous psychological burden for the affected persons. To avoid victimization there is an urgent need for more information about the differential diagnoses of sexual abuse and a call for interdisciplinary co-operation when evaluating abnormal anogenital findings in children.

Impact of freezing and ethanol preservation techniques on the stable isotope analysis of humpback whale (Megaptera novaeangliae) skin.

RATIONALE: Distinct techniques employed to preserve different types of tissues may affect stable isotope analyses conducted on samples, and this is critical when field work takes place in remote areas. To investigate this, the stable isotope ratios (δ13 C and δ15 N values) obtained using two methods commonly used to preserve humpback whale (and other cetaceans) skin samples were compared. METHODS: A total of 54 pairs of skin samples of humpback whales from the southern Baja California Peninsula, Mexico, were preserved in ethanol (90%) and by freezing, between 2007 and 2009. The δ13 C and δ15 N values were determined using a PDZ Europa ANCA-GSL elemental analyzer interfaced to a PDZ Europe 20-20 isotope ratio mass spectrometer. Parametric and nonparametric tests were used to compare the isotopic results. RESULTS: A significant (t = 4.93; p = 0.000003) variation of −0.92‰ was found between the mean δ13 C values in ethanol (from −19.38‰ to −16.07‰; mean = −17.86‰) and freezing (from −20.67‰ to −16.44‰; mean = −18.78‰) techniques. No significant (U = 1314, p = 0.38) differences were observed in the δ15 N values. The δ13 C values were compared between preservation methods for each of the three years under analysis. Significant differences were observed in 2007 (t = 3.45; p = 0.0012) and 2008 (t = 3.13; p = 0.0030), but not for 2009 (t = 1.66; p = 0.12). CONCLUSIONS: Based on the results of this study, the use of ethanol to preserve humpback whale skin samples collected for stable isotope analysis is not recommended, particularly regarding the analysis of δ13 C values. This study serves as a point of reference for future research on humpback whales or other whales involving skin samples preserved by freezing or in ethanol.

What do we know about taper corrosion in total hip arthroplasty?

Mechanically assisted crevice corrosion (MACC) at metal/metal modular junctions in which at least one of the components is fabricated from cobalt-chromium alloy, has reemerged as a potential clinically significant complication in total hip arthroplasty. The clinical manifestation of MACC may include the development of an adverse local tissue reaction (ALTR), similar to what has been described in association with metal-on-metal bearing total hip and resurfacing arthroplasty. The clinical presentation of MACC-associated ALTRs may include pain and possibly late recurrent dislocations. Abnormal metal artifact reduction sequence magnetic resonance images and elevated serum metal levels (cobalt elevations out of proportion to chromium elevations) can be helpful in the diagnosis of these MACC-associated ALTRs.

Gray whale (Eschrichtius robustus) post-mortem findings from December 2018 through 2021 during the Unusual Mortality Event in the Eastern North Pacific.

Beginning in December 2018, increased numbers of gray whale (Eschrichtius robustus) strandings were reported along the west coast of Mexico, the United States, and Canada, prompting declaration of a gray whale Unusual Mortality Event (UME) by the United States National Marine Fisheries Service. Although strandings declined in 2020 and 2021 from a peak in 2019, the UME is still ongoing as of fall 2023. Between 17 December 2018 and 31 December 2021, 503 animals stranded along the west coast of North America, with 226 strandings in Mexico, 71 in California, 12 in Oregon, 56 in Washington, 21 in British Columbia, and 117 in Alaska. These included 187 males, 167 females, and 149 whales of undetermined sex; and 193 adults, 194 subadults, 40 calves, 1 fetus, and 75 whales of undetermined age class. We report on 61 of the 503 carcasses (12%) that had external and internal gross necropsy and/or histopathology data: of these 61 whales, findings that contributed to death were identified in 33 (54%) whales. Sixteen of the 61 (26%) were severely emaciated. Gross lesions of blunt force trauma consistent with vessel strike were identified in 11 of the 61 animals (18%), only two of which were emaciated. Two whales (3%) were entangled at time of death, and one died from entrapment. Signs of killer whale (Orcinus orca) interaction were documented in 19 of the 61 animals; five were deemed from recent interactions and three (5%) likely contributed to mortality. A specific cause of death could not be identified in 28 of 61 whales (46%). Additionally, logistical challenges and the advanced state of decomposition of most examined carcasses precluded detection of potential infectious or toxic causes of morbidity or mortality. Up to 2016, the eastern North Pacific population of gray whale population had generally been increasing since the cessation of historic whaling and a prior UME in 1999-2000. However, recent abundance and calf production estimates have declined, a trend that overlaps the current UME. The relative contributions of carrying capacity, environmental change, prey shifts, and infectious, toxic, and other processes to the increased gray whale mortalities have not yet been resolved. Nevertheless, the marked temporal increase in strandings, including findings of malnutrition in some of the whales, along with low calf production, likely represent consequences of complex and dynamic ecological interactions in the ocean impacting the population.

Whistle characterization of long-beaked common dolphin (Delphinus delphis bairdii) in La Paz Bay, Gulf of California.

Long-beaked common dolphin (Delphinus delphis bairdii) distribution is limited to the Eastern North Pacific Ocean. Its whistle repertoire is poorly investigated, with no studies in the Gulf of California. The aim of the present study is to characterize the whistles of this species and compare their parameters with different populations. Acoustic monitoring was conducted in La Paz Bay, Gulf of California. Recordings were inspected in spectrogram view in Raven Pro, selecting good quality whistles (n = 270). In the software Luscinia, contours were manually traced to obtain whistle frequencies and duration. Number of steps, inflection points and contour type were visually determined. We calculated the descriptive statistics of the selected whistle parameters and we compared the results with a dolphins population from the Eastern Pacific Ocean. Permutational multivariate analysis of variance (PERMANOVA) was performed to test the intraspecific variation of the whistle parameters among groups. In the present study the mean values (±SD) of the whistle parameters were: maximum frequency = 14.13 ± 3.71 kHz, minimum frequency = 8.44 ± 2.58 kHz and duration = 0.44 ± 0.31 s. Whistles with the upsweep contour were the most common ones (34.44%). The coefficient of variation (CV) values for modulation parameters were high (>100%), in accordance with other studies on dolphins. Whistle parameters showed significant differences among groups. Finally, ending and maximum frequencies, duration and inflection points of the whistles recorded in the present study were lower compared with the parameters of the long-beaked common dolphins from the Eastern Pacific Ocean. This study provides the first whistle characterization of long-beaked common dolphin from the Gulf of California and it will help future passive acoustic monitoring applications in the study area.

Differences in the whistles of two ecotypes of bottlenose dolphins from the Gulf of California.

Intraspecific whistle variation in dolphins has been explained in the context of geographical isolation, soundscape, and social structure. Whistles of two ecotypes of bottlenose dolphins from La Paz Bay, Gulf of California, were analyzed. Both ecotypes showed similar whistle contours. However, they could be identified by contour maximum frequency which was predominantly above 15 kHz for oceanic dolphins and below 15 kHz for coastal dolphins. The different whistle frequencies of the two ecotypes could result from differences in group size and acoustic characteristics of their respective habitats, suggesting potential future passive acoustic monitoring applications.

Low-dose carboplatin modifies the tumor microenvironment to augment CAR T cell efficacy in human prostate cancer models.

Chimeric antigen receptor (CAR) T cells have transformed the treatment landscape for hematological malignancies. However, CAR T cells are less efficient against solid tumors, largely due to poor infiltration resulting from the immunosuppressive nature of the tumor microenvironment (TME). Here, we assessed the efficacy of Lewis Y antigen (LeY)-specific CAR T cells in patient-derived xenograft (PDX) models of prostate cancer. In vitro, LeY CAR T cells directly killed organoids derived from androgen receptor (AR)-positive or AR-null PDXs. In vivo, although LeY CAR T cells alone did not reduce tumor growth, a single prior dose of carboplatin reduced tumor burden. Carboplatin had a pro-inflammatory effect on the TME that facilitated early and durable CAR T cell infiltration, including an altered cancer-associated fibroblast phenotype, enhanced extracellular matrix degradation and re-oriented M1 macrophage differentiation. In a PDX less sensitive to carboplatin, CAR T cell infiltration was dampened; however, a reduction in tumor burden was still observed with increased T cell activation. These findings indicate that carboplatin improves the efficacy of CAR T cell treatment, with the extent of the response dependent on changes induced within the TME.

Microplastic occurrence and phthalate ester levels in neuston samples and skin biopsies of filter-feeding megafauna from La Paz Bay (Mexico).

The impacts of microplastics on filter feeders megafauna have recently received increased attention. These organisms are potentially exposed to plastic ingestion and the release of added/sorbed contaminants during feeding activities. An assessment of microplastic abundance and the chemical impact of Phthalates esters (PAEs) were performed in neustonic samples and skin biopsies of Balaenoptera physalus and Rhincodon typus inhabiting the Gulf of California (Mexico). Sixty-eight percent of the net tows contained plastics with a maximum of 0.24 items/m3 mainly composed of polyethylene fragments. PAE levels were detected both in environmental and skin biopsy samples, with the highest values in the fin whale specimens (5291 ng/g d.w). Plasticizer fingerprint showed a similar distribution pattern between neustonic samples and filter-feeding species, with DEHP and MBP having the highest concentrations. The detection of PAE levels confirmed their potential role as plastic tracers and give preliminary information about the toxicological status of these species feeding in La Paz Bay.

The genomic footprint of whaling and isolation in fin whale populations.

Twentieth century industrial whaling pushed several species to the brink of extinction, with fin whales being the most impacted. However, a small, resident population in the Gulf of California was not targeted by whaling. Here, we analyzed 50 whole-genomes from the Eastern North Pacific (ENP) and Gulf of California (GOC) fin whale populations to investigate their demographic history and the genomic effects of natural and human-induced bottlenecks. We show that the two populations diverged ~16,000 years ago, after which the ENP population expanded and then suffered a 99% reduction in effective size during the whaling period. In contrast, the GOC population remained small and isolated, receiving less than one migrant per generation. However, this low level of migration has been crucial for maintaining its viability. Our study exposes the severity of whaling, emphasizes the importance of migration, and demonstrates the use of genome-based analyses and simulations to inform conservation strategies.

Development of a novel protocol for isolation and purification of human granulosa cells.

PURPOSE: To develop an optimal method of isolation and purification of human granulosa cells from ovarian follicular fluid. METHODS: Follicular fluid was collected from patients undergoing oocyte retrieval. A series of isolation and purification techniques was performed, involving density gradient centrifugation and use of different antibody-bead complexes. RESULTS: The highest percent yield of live purified granulosa cells came from density gradient centrifugation using sucrose polymer followed by positive selection of granulosa cells using primary antibody to MISRII and secondary antibody coupled to iron oxide beads. CONCLUSIONS: A novel protocol for granulosa cell purification has been developed yielding samples that are largely free of nondesirable cells. This protocol provides a purification solution, especially for patient samples that have significant RBC contamination.