Annual fecundity, batch fecundity, and oocyte atresia of Atka mackerel (Pleurogrammus monopterygius) in Alaskan waters

Annual potential fecundity, batch fecundity, and oocyte atresia were estimated for Atka mackerel (Pleurogrammus monopterygius) collected in Alaskan waters during 1993−94. Atka mackerel were assumed to be determinate spawners on the basis of decreasing fecundity after batch spawning events. Histological examination of the ovaries indicated that oocytes in the vitellogenic stage and higher had been spawned in the current spawning season. For an average female of 40 cm, potential annual fecundity was estimated to be 41,994 eggs, average batch size (i.e., batch fecundity) was estimated to be 6689 eggs, and there were 6.13 batches per spawning season. Atresia was estimated by examining postspawning specimens and was found to be substantial. The average amount of atresia for a 40-cm fish was estimated to be 11,329 eggs, resulting in an estimated realized fecundity of only 30,664 eggs and 4.64 batches of eggs per spawning season

An atlas of reproductive development in rockfishes, genus Sebastes

The genus Sebastes consists of over 100 fish species, all of which are viviparous and long-lived. Previous studies have presented schemes on the reproductive biology of a single targeted species of the genus Sebastes, but all appear to possess a similar reproductive biology as evidenced by this and other studies. This atlas stages major events during spermatogenesis, oogenesis, and embryogenesis, including atresia, in six species of Sebastes (S. alutus, S. elongatus, S. helvomaculatus, S. polyspinis, S. proriger, and S. zacentrus). Our study suggests that the male reproductive cycle of Sebastes is characterized by 11 phases of testicular development, with 10 stages of sperm development and 1 stage of spermatozoa atresia. Ovarian development was divided into 12 phases, with 10 stages of oocyte development, 1 stage of embryonic development, and 1 stage of oocyte atresia. Embryonic development up to parturition was divided into 33 stages following the research of Yamada and Kusakari (1991). Reproductive development of all six species examined followed the developmental classifications listed above which may apply to all species of Sebastes regardless of the number of broods produced annually. Multiple brooders vary in that not all ova are fertilized and progress to embryos; a proportion of ova are arrested at the pre-vitellogenic stage. Reproductive stage examples shown in this atlas use S. elongates for spermatic development, S. proriger for oocyte development, and S. alutus for embryological development, because opportunistic sampling only permitted complete analysis of each respective developmental phase for those species. The results of this study and the proposed reproductive phases complement the recommended scheme submitted by Brown-Peterson et al. (2011), who call for a standardization of terminology for describing reproductive development of fishes

Lessons on Marine Protected Area Management in Northern Boreal Regions from the United States and Norway

In comparison to tropical reef systems, relatively few marine protected areas (MPA’s) exist in temperate or subarctic systems (e.g., North Pacific and North Atlantic) where species diversity is lower, abundance of individual species is often higher, and many fish species exhibit large amounts of movement during one or more of their life stages, especially as adults. A review of MPA’s in three northern areas—the Northwest Atlantic, Northeast Atlantic, and the Northeast Pacific—indicates that MPA’s can be useful management tools towards fisheries management and habitat conservation. However, achieving fishery goals, such as sustainable use of the fisheries resources, will depend on population abundance (relative to unfished conditions) and fish behavior and movement. For example, depleted populations of stationary species such as Atlantic sea scallops, Placopecten magellanicus, in the Northeast Atlantic and European lobster, Homarus grammarus, in the North Sea have responded positively to small MPA’s, whereas migratory offshore Atlantic cod, Gadus morhua, and Pacific cod, Gadus macrocephalus, apparently do not appear to benefit from closed areas because of movement into fished areas. Efficient habitat conservation requires detailed habitat mapping on relevant spatial scales. In northern boreal systems with large remote areas, this information is difficult and expensive to access. An alternative strategy of closing and protecting unexploited areas has worked well for the Aleutian Island coral closure area in Alaska. MPA’s can be effective fisheries management tools when the species to be protected have been depleted and show a small to moderate level of movement, and reproductive success is ensured. MPA’s can be effective at preserving habitat when the design is based on scientific information and takes into account the impact on the user groups.publishedVersio

Prognosis for patients with amyotrophic lateral sclerosis: development and validation of a personalised prediction model

Summary Background Amyotrophic lateral sclerosis (ALS) is a relentlessly progressive, fatal motor neuron disease with a variable natural history. There are no accurate models that predict the disease course and outcomes, which complicates risk assessment and counselling for individual patients, stratification of patients for trials, and timing of interventions. We therefore aimed to develop and validate a model for predicting a composite survival endpoint for individual patients with ALS. Methods We obtained data for patients from 14 specialised ALS centres (each one designated as a cohort) in Belgium, France, the Netherlands, Germany, Ireland, Italy, Portugal, Switzerland, and the UK. All patients were diagnosed in the centres after excluding other diagnoses and classified according to revised El Escorial criteria. We assessed 16 patient characteristics as potential predictors of a composite survival outcome (time between onset of symptoms and non-invasive ventilation for more than 23 h per day, tracheostomy, or death) and applied backward elimination with bootstrapping in the largest population-based dataset for predictor selection. Data were gathered on the day of diagnosis or as soon as possible thereafter. Predictors that were selected in more than 70% of the bootstrap resamples were used to develop a multivariable Royston-Parmar model for predicting the composite survival outcome in individual patients. We assessed the generalisability of the model by estimating heterogeneity of predictive accuracy across external populations (ie, populations not used to develop the model) using internal–external cross-validation, and quantified the discrimination using the concordance (c) statistic (area under the receiver operator characteristic curve) and calibration using a calibration slope. Findings Data were collected between Jan 1, 1992, and Sept 22, 2016 (the largest data-set included data from 1936 patients). The median follow-up time was 97·5 months (IQR 52·9–168·5). Eight candidate predictors entered the prediction model: bulbar versus non-bulbar onset (univariable hazard ratio [HR] 1·71, 95% CI 1·63–1·79), age at onset (1·03, 1·03–1·03), definite versus probable or possible ALS (1·47, 1·39–1·55), diagnostic delay (0·52, 0·51–0·53), forced vital capacity (HR 0·99, 0·99–0·99), progression rate (6·33, 5·92–6·76), frontotemporal dementia (1·34, 1·20–1·50), and presence of a C9orf72 repeat expansion (1·45, 1·31–1·61), all p<0·0001. The c statistic for external predictive accuracy of the model was 0·78 (95% CI 0·77–0·80; 95% prediction interval [PI] 0·74–0·82) and the calibration slope was 1·01 (95% CI 0·95–1·07; 95% PI 0·83–1·18). The model was used to define five groups with distinct median predicted (SE) and observed (SE) times in months from symptom onset to the composite survival outcome: very short 17·7 (0·20), 16·5 (0·23); short 25·3 (0·06), 25·2 (0·35); intermediate 32·2 (0·09), 32·8 (0·46); long 43·7 (0·21), 44·6 (0·74); and very long 91·0 (1·84), 85·6 (1·96). Interpretation We have developed an externally validated model to predict survival without tracheostomy and non-invasive ventilation for more than 23 h per day in European patients with ALS. This model could be applied to individualised patient management, counselling, and future trial design, but to maximise the benefit and prevent harm it is intended to be used by medical doctors only. Funding Netherlands ALS Foundation

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Effects of Maternal Growth on Fecundity and Egg Quality of Wild and Captive Atka Mackerel

Trade-offs in energy allocation between growth and reproduction can result in variations in reproductive potential in fish with differing growth patterns. Spawning biomass is often used as a proxy for reproductive potential on the assumption that fecundity is directly proportional to body weight. We examined variations in the reproductive potential of Atka mackerel Pleurogrammus monopterygius by studying the effect of differential growth and condition patterns on fecundity, atresia, and egg energy. Fecundity and egg energy were determined for fish from two geographic areas, Seguam Pass and Amchitka Island, Alaska, and compared with those of fish held in captivity. These Atka mackerel showed distinct differences in growth and condition, with weight at length and length at age being the highest among captive fish, intermediate among fish from Seguam Pass, and lowest among fish from Amchitka Island. Realized fecundity showed that on average captive fish spawned seven batches, fish from Seguam Pass six batches, and fish from Amchitka Island five batches. For wild fish, potential and realized fecundity at length or age was significantly higher at Seguam Pass than at Amchitka Island, whereas the fecundity-at-weight relationship did not differ by area, suggesting that weight is a better predictor of fecundity than length or age. Atresia and batch fecundity by length or weight did not differ by area, suggesting that the variation in fecundity is better explained by the variation in batch number than by batch size. Oocyte dry weight was higher for captive fish than for wild fish, whereas batch order did not significantly affect oocyte dry weight. Increased potential fecundity, realized fecundity, and oocyte quality in Atka mackerel females were strongly related to body size, indicating that growth differences and maternal feeding success impact the fecundity and oocyte quality of Atka mackerel. Therefore, changes in growth and condition patterns need to be taken into account to accurately estimate the reproductive potential of this species

Geolocation of a demersal fish (Pacific cod) in a high-latitude island chain (Aleutian Islands, Alaska)

Abstract Background Fish geolocation methods are most effective when they are customized to account for species behavior and study area characteristics. Here, we provide an example of customizing a hidden Markov model (HMM) for reconstructing movement pathways of a high-latitude demersal fish species in a remote island chain using Pop-up Satellite Archival Tag (PSAT) data. Adult Pacific cod were tagged with PSATs while occupying winter spawning grounds in the Aleutian Islands in February 2019. We adapted a demersal fish application of the HMM to (1) add light-based longitude to the data likelihood model, (2) account for possible off-bottom behavior of demersal fishes in the maximum daily depth likelihood, and (3) modify the model framework to accommodate convoluted island topography in the study area. A simulation study was conducted to explore the two primary modifications to the model framework, reflecting boundary for the movement kernel and the Viterbi method of pathway reconstruction, under known conditions. Results Geolocation was performed on satellite-transmitted and detailed archival data sets from 6 adult Pacific cod at liberty for 21–277 days. Migration from winter spawning to summer foraging areas (range 60–395 km) was detected for the 4 tagged fish that were at liberty for more than 90 days. Light-based longitude was the primary geolocation variable for detecting migrations with precision (root mean square error) estimates of 0.56 degrees during winter and 1.3 degrees during the summer. Simulation studies confirmed the effectiveness of model framework modifications and generated guidelines for use in specific applications. Conclusions This study demonstrates that post-spawning migrations of Pacific cod in the Aleutian Islands can be detected and characterized using PSAT data. Initial insights into migrations, summer foraging areas, and associated development of appropriate analysis tools will support future Pacific cod movement studies in the Aleutian Islands as well as other regions of Alaska. The adaptations to the HMM presented here will benefit current and future research on demersal fish in other regions as well as fish species that occupy areas with convoluted shorelines or island chain topography

Dynamics of total, linear nonintegrated, and integrated HIV-1 DNA in vivo and in vitro

BACKGROUND: In patients infected with human immunodeficiency virus type 1 (HIV-1), HIV-1 DNA persists during highly active antiretroviral treatment, reflecting long-lived cellular reservoirs of HIV-1. Recent studies report an association between HIV-1 DNA levels, disease progression, and treatment outcome. However, HIV-1 DNA exists as distinct molecular forms that are not distinguished by conventional assays. METHODS: We analyzed HIV-1 RNA levels in plasma, CD4 cell counts, and levels of integrated and nonintegrated HIV-1 DNA in peripheral blood mononuclear cells (PBMCs) from patients with early or chronic infection before and during antiretroviral treatment. We also studied HIV-1 DNA decay in primary CD4 T cells infected in vitro. HIV-1 DNA was analyzed using an assay that is unaffected by the location of HIV-1 integration sites. RESULTS: HIV-1 RNA levels and total HIV-1 DNA levels decayed rapidly in patients during receipt of suppressive antiretroviral therapy. Ratios of total HIV-1 DNA levels to integrated HIV-1 DNA levels were high before initiation of therapy but diminished during therapy. Levels of linear nonintegrated HIV-1 DNA decayed rapidly in vitro (t (1/2) = 1- 4.8 days). CONCLUSION: Total HIV-1 DNA decays rapidly with suppression of virus replication in vivo. Clearance of HIV-1 DNA during the first 6 months of therapy reflects a disproportionate loss of nonintegrated HIV-1 DNA genomes, suggesting that levels of total HIV-1 DNA in PBMCs after prolonged virus suppression largely represent integrated HIV-1 genomes