Explaining prehistoric variation in the abundance of large prey: a zooarchaeological analysis of deer and rabbit hunting along the Pecho Coast of Central California

journal articleThree main hypotheses are commonly employed to explain diachronic variation in the relative abun dance of remains of large terrestrial herbivores: (1) large prey populations decline as a function of anthro pogenic overexploitation; (2 ) large prey tends to increase as a result of increasing social payoffs; and (3) proportions of large terrestrial prey are dependent on stochastic fluctuations in climate. This paper tests predictions derived from these three hypotheses through a zooarchaeological analysis of eleven temporal components from three sites on central California's Pecho Coast. Specifically, we examine the trade offs between hunting rabbits (Sylvilagus spp.) and deer (Odocoileus hemionus) using models derived from human behavioral ecology. The results show that foragers exploited a robust population of deer through out most of the Holocene, only doing otherwise during periods associated w ith climatic trends unfavor able to larger herbivores. The most recent component (Late Prehistoric/Contact era) shows modest evidence of localized resource depression and perhaps greater social benefits from hunting larger prey; we suggest that these final changes resulted from the introduction of bow and arrow technology. Overall, results suggest that along central California's Pecho Coast, density independent factors described as cli matically mediated prey choice best predict changes in the relative abundance of large terrestrial herbi vores through the Holocene

La tenuitá del fatto nel processo penale. (dall'esigenza di protezione del minore di età alla valorizzazione dell'economia processuale?)

Il mio lavoro tratta sia dell'articolo 27 del dpr 448/1988 processo minorile,sia dell'articolo 131-bis cp inserito nel 2015. Entrambi risaltano l'argomento della tenuità del fatto ma ovviamente con le relative peculiarità

Trans-Holocene Marine Mammal Exploitation on San Clemente Island, California: A Tragedy of the Commons Revisited

Occupied from ca. 7040 B.C. to AD. 1400, the Eel Point Site (CA-SCLI-43) on San Clemente Island, California represents one of the longest sequences of near-continuous marine resource exploitation on the west coast of North America. Faunal remains suggest transitions from heavy exploitation of fur seals and sea lions during the early Holocene, to increased hunting of cetaceans at mid-Holocene, to a focus on sea otters and fish during the late Holocene. These trends are consistent with patterns of overexploitation and economic intensification on the California and Oregon mainland, but they also suggest watercraft-based hunting earlier on the island than elsewhere. Fur seal and sea lion bones mainly represent females and juveniles, indicating that exploitation of island rookeries was guided more by self-interest than by principles of game conservation. Two intervals of temporary site abandonment, ca. 6150-3970 B.C. and AD. 1020-1400, were both followed by periods of increased marine mammal exploitation and may reflect intervals during which marine mammal populations rebounded. Broad-scale diachronic trends in the zooarchaeological remains do not correlate with flux in paleo-sea temperatures and are best interpreted as products of overhunting and increased use of watercraft over time

Immunoistochemical expression of PD-1 and PD-L1 in bone marrow biopsies of patients with acute myeloid leukemia

Background. Haematological and non-haematological malignancies are able to escape the host immune by the capacity to hijack the immune check-points. Several immune check-point molecules are known, such as T cell immunoglobulin mucin-3 (TIM-3), cytotoxic T-cell antigen-4 (CTLA-4), programmed death-1 (PD-1) with its ligand PD-L1 and others.1 The function of these immune check-points is to prevent the damage resulting from an excessive activation of the immune response in the setting of chronic antigenic stimulation, thus leading to autoimmune phenomena, as proved in knock-out mice models. PD-1 is normally present on activated T lymphocytes membrane, acting as a negative costimulatory receptor. PD-L1 is constitutively expressed at low levels by resting lymphocytes, antigen presenting cells and certain immunologically privileged tissues like placenta and testis. PD-L1 expression can be induced as well. In an inflammatory/infective context when T cells recognize antigens expressed by MHC-complex they start to produce inflammatory cytokines. The resulting inflammation leads to the expression of PD-L1 by hematopoietic, epithelial and endothelial cells, activating PD-1 on the surface of T-cells and therefore blocking the immune response. Previous studies have found out that PD-1 is highly expressed on T-reg cells and their binding with PD-L1 enhances suppressor T-reg functions2,3; the activation of PD-1/PD-L1 pathway reduces the lytic capacity of NK cells and B cell antibody production. In solid neoplasms PD-L1 expression by cancer cells and persistent up-regulation of PD-1 by tumourinfiltrating lymphocytes is common45. All these findings brought to the development of check-point inhibitors in the contest of solid tumors and lymphoproliferative neoplasms such as lymphoma and myeloma where the immune checkpoint blockade treatment have shown efficacy in refractory/relapsed neoplasms6. Few investigations only have been conducted on the role of PD1/PD-L1 in myeloid neoplasms, such as acute myeloid leukemia, a haematological cancer characterised by high-risk of relapse and poor prognosis. In leukemia, the bone marrow serves as a sanctuary for neoplastic cells, these cells interact with the tumour microenvironment (TME), constituted by stromal cells, endothelial cells and immune cells. The marked activation of the PD-1/PD-L1 pathway contributes to the maintenance of an immunosuppressive microenvironment. In fact, blasts are able, through the production of immunoinhibitory factors, to suppress the function of immunosurveillance and immuno-elimination of the tumor by the effector T cells. The effector T cells are "exhausted" in their capacity to secrete granzyme B, perforine and interferon gamma, and there is an upregulation of the T-reg functions, in addition to the presence of myeloid-derived suppressor cells7. PD-L1 expression and his link with PD-1 on activated lymphocytes results in an impaired antitumoral activity in murine models8. Zhang et al. investigated the role of PD-1/PD-L1 engagement in murine AML showing that PD-1-/-mice generated augmented antitumoral response in comparison with wild type mice. Similar results were obtained using anti-PD-L1 antibodies.9 A study from Zhou et al. reported how the function of adoptively transferred AML-reactive CTLs was reduced by AML-associated Tregs and how Treg depletion followed by PD-1/PD-L1 blockade showed efficacy for AML eradication in murine models.10 Objective of the study. To assess the presence of PD-1 and PD-L1 positive cells, by immunohistochemistry, in bone marrow biopsies of patients with AML. Material and methods. Four micron thickness sections were obtained from the formalin-fixed paraffin-embedded specimens. Haematoxylin-eosin staining was performed to assess the morphologic features of bone marrow. Immunohistochemical stainings were performed using a Ventana Benchmark Ultra automated staining instrument according to the manufacturer’s recommendations, using anti-PD-1 (clone NAT105, Ventana) and anti-PD-L1 (clone 22C3, Dako) antibodies. Results. We obtained 34 bone marrow trephine biopsies from newly diagnosed AML patients, 17 males and 17 females with a 67.3 mean age. We used 10 healthy bone marrow specimens as normal controls. None out of 10 control bone marrows resulted positive for either PD-1 or PD-L1 expressing cells as expected. Eleven out of 34 AML bone marrows (32,4%) showed at least 1% of PD-L1 positive cells (fig.2 b,d,f), while 6 AML bone marrow samples (17,6%) were positive for at least 1% of PD-1+ cells (fig. 1 b). Discussion. Despite the presence of relevant preclinical data regarding the role of immune check-points, few studies to evaluate the PD1/PDL1 axis have been conducted in myeloid neoplasm. Jia et al. performed flow cytometry analysis on PBMCs and BMMCs of 22 newly diagnosed AML patients and observed a significantly increased frequency of PD-1 expressing CD8 T cells in bone marrow compared to peripheral blood, suggesting a more exhausted status of these cells in relation to the suppressivePaper environment11. Dail et al. measured PD-L1 expression in 7 AML patients using immunohistochemistry and flow cytometry and found that PD-L1 was detectable (>2% cells) in all patients.12 Yang et al. assessed 45 bone marrow biopsies of MDS, CMML and AML patients and found that leukemic blasts of 9 patients (20%) were PD-L1+, while 3 (7%) were positive for PD-1. All 4 controls tested were negative for both PD-1 and PD-L1.13 Daver et al. measured PD-1 expression on bone marrow aspirates of 74 AML patients using flow cytometry. The results showed higher PD-1 expression compared to healthy controls (n=8).14Acceped To our this is the largest study evaluating by immunohistochemistry the expression of PD-1 and PDL1 in AML bone marrows and shows a significative positivity of the activation of the PD-1/PD-L1 pathway which gives a rationale to further studies regarding the charateristics of the cells involved in the PD-1/PD-L1 pathway and the immunosuppressive microenvironment. An implementation of the PD-1/PD-L1 pathway evaluation in clinical setting could have prognostic significance since the expression of PD-L1 by AML blasts has been associated with poor-risk and intermediate-risk AML15, furthermore immune checkpoint inhibitors have shown promising results in maintenance treatment of high-risk AML16, underlining not only a prognostic but also therapeutic value of the PD1/PD-L1 evaluation

Spatial Distribution of Aedes aegypti Oviposition Temporal Patterns and Their Relationship with Environment and Dengue Incidence

Aedes aegypti, the mosquito species transmitting dengue, zika, chikungunya and yellow fever viruses, is fully adapted to thrive in urban areas. The temporal activity of this mosquito, however, varies within urban areas which might imply different transmission risk. In this work, we hypothesize that temporal differences in mosquito activity patterns are determined by local environmental conditions. Hence, we explore the existence of groups of temporal patterns in weekly time series of Ae. aegypti ovitraps records (2017–2019) by means of time series clustering. Next, with the aim of predicting risk in places with no mosquito field data, we use machine learning classification tools to assess the association of temporal patterns with environmental variables derived from satellite imagery and predict temporal patterns over the city area to finally test the relationship with dengue incidence. We found three groups of temporal patterns that showed association with land cover diversity, variability in vegetation and humidity and, heterogeneity measured by texture indices estimated over buffer areas surrounding ovitraps. Dengue incidence on a neighborhood basis showed a weak but positive association with the percentage of pixels belonging to only one of the temporal patterns detected. The understanding of the spatial distribution of temporal patterns and their environmental determinants might then become highly relevant to guide the allocation of prevention and potential interventions. Further investigation is still needed though to incorporate other determinants not considered here.Fil: Andreo, Verónica Carolina. Comision Nacional de Actividades Espaciales. Instituto de Altos Estudios Espaciales "Mario Gulich"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; ArgentinaFil: Porcasi Gomez, Ximena. Comision Nacional de Actividades Espaciales. Instituto de Altos Estudios Espaciales "Mario Gulich"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; ArgentinaFil: Guzmán, Claudio Daniel. Provincia de Córdoba. Ministerio de Salud; ArgentinaFil: López, Laura. Provincia de Córdoba. Ministerio de Salud; ArgentinaFil: Scavuzzo, Carlos Matias. Comision Nacional de Actividades Espaciales. Instituto de Altos Estudios Espaciales "Mario Gulich"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; Argentin

Intestinal parasitic infections in a community from Pampa del Indio, Chaco (Argentina) and their association with socioeconomic and environmental factors

Neglected tropical diseases are a group of 20 disabling diseases, which, in particular, are the most common chronic infections in the most vulnerable people. This study aimed to characterize the infection by intestinal parasites (IPs) in dwellings from a peri-urban neighborhood in Pampa del Indio, Chaco (Argentina), and its association with socioeconomic and environmental variables. Single stool samples were collected from all individuals older than 1 year through household visits and processed using coprological sedimentation and flotation techniques. Standardized questionnaires were used at the household level to collect socio-economic information. Environmental variables were obtained from the Planetscope image, Landsat 8 images and remote sensors, while land-use layers were obtained through the use of a maximum likelihood algorithm. Stool samples were provided by 314 individuals. The prevalence of IPs found was 30.6% (n = 96), with a predominance of Giardia lamblia (12.7%, n = 40) and Hymenolepis nana (7.6%, n = 24). The only soil-transmitted helminth found was Strongyloides stercoralis with a 2.5% prevalence (n = 8). Individuals of adult age (> 18 years) were 0.65 times less likely to present parasitic infections with respect to children and adolescents. The only environmental variable that was closely associated with the presence of IPs, was the Normalized Difference Water Index (NDWI), a measure of humidity; being higher around houses with positive individuals. Most of the IPs found in this study were of water-borne transmission and those transmitted directly from person-to-person, therefore fecal contamination is present. We believe that the low prevalence of STH in this area, which requires a passage through the soil, is related to the environmental characteristics, which are unsuitable for the development/permanence of the infective stages of these parasites. The geospatial data and tools used herein proved to be useful for the study of the relationship between the different factors that influence the presence of IPs in a community, from an eco-health approach.Fil: Scavuzzo, Carlos Matias. Comision Nacional de Actividades Espaciales. Instituto de Altos Estudios Espaciales "Mario Gulich"; Argentina. Fundación Mundo Sano; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Delgado, Cintia. Fundación Mundo Sano; ArgentinaFil: Goy, Marcia. Hospital Dr. Dante Tardelli; ArgentinaFil: Crudo, Favio. Fundación Mundo Sano; ArgentinaFil: Porcasi, Ximena. Comision Nacional de Actividades Espaciales. Instituto de Altos Estudios Espaciales "Mario Gulich"; ArgentinaFil: Periago, Maria Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación Mundo Sano; Argentin

CD1A-positive cells and HSP60 (HSPD1) levels in keratoacanthoma and squamous cell carcinoma

CD1a is involved in presentation to the immune system of lipid antigen derived from tumor cells with subsequent T cell activation. Hsp60 is a molecular chaperone implicated in carcinogenesis by, for instance, modulating the immune reaction against the tumor. We have previously postulated a synergism between CD1a and Hsp60 as a key factor in the activation of an effective antitumor immune response in squamous epithelia. Keratoacantomas (KAs) are benign tumors that however can transform into squamous cell carcinomas (SCCs), but the reasons for this malignization are unknown. In a previous study, we found that CD1a-positive cells are significantly more numerous in KA than in SCC. In this study, we analyzed a series of KAs and SCCs by immunohistochemistry for CD1a and Hsp60. Our results show that the levels of both are significantly lower in KA than in SCC and support the hypothesis that KA may evolve towards SCC if there is a failure of the local modulation of the antitumor immune response. The data also show that immunohistochemistry for CD1a and Hsp60 can be of help in differential diagnosis between KAs and well-differentiated forms of SCC

Associations between Notch-2, Akt-1 and HER2/neu expression in invasive human breast cancer: a tissue microarray immunophenotypic analysis on 98 patients.

Objective: We aimed to investigate the existence of associations between well-established and newly recognized biological and phenotypic features of breast cancer involved in tumor progression and prognosis. Methods: Ninety-eight cases of invasive breast cancer were assessed for the immunohistochemical expression of estrogen and progesterone receptors, Ki-67, HER2, Akt-1, and Notch-2, using the tissue microarray technique. Data regarding tumor histotype, histological grade, tumor size and lymph node status were collected for each patient and included in the analysis. Results: Several significant associations between histological and/or immunophenotypic features came from the analysis of our data. Positive associations were observed between estrogen and progesterone receptors, tumor grade and proliferation index, tumor grade and HER2, Akt-1 and estrogen receptors, and Notch-2 and HER2. Inverse associations were noted between hormone receptors and tumor grade, hormone receptors and HER2, Akt-1 and tumor grade, and Akt-1 and nodal invasion. Conclusions: Our results, showing the existence of a number of estrogen receptor-positive tumors with Akt-1 expression, better degree of differentiation, and no lymph node involvement, along with the presence of HER2- positive tumors with strong Notch-2 expression, support the role of Notch and Akt in breast cancer progression and suggest that they may also represent new appealing therapeutic targets

Predictive role of the p16 immunostaining pattern in atypical cervical biopsies with less common high risk hpv genotypes

P16 immunostaining is considered a useful surrogate of transcriptionally active high‐risk (hr) HPV infection. Only strong and widespread “block‐like” immunoreactivity is considered specific, whereas weak/focal p16 positive immunostaining is considered not specific, and follow‐up and HPV molecular detection is not indicated. The aim of the study was to evaluate the presence of HPV DNA and Ki67 immunostaining in 40 cervical atypical biopsies (CALs) with mild and focal histological features suggestive of HPV infection—20 cases with weak/focal p16 positive immunoreactivity and 20 cases negative for p16 expression. In 16/20 weak/focal p16 positive CALs (80%), the INNO‐LiPA HPV genotyping detected hrHPV genotypes (HPV 31, 51, 56, 59, 26, 53, 66, 73, and 82). Co‐infection of two or more hrHPV genotypes was often evidenced. HPV16 and 18 genotypes were never detected. Ki67 immunostaining was increased in 10/20 cases (50%). In 19/20 p16 negative CALs, hrHPV infection was absent and Ki67 was not increased. These results suggest that weak/focal p16 immunostaining represents the early stage of transcriptionally active infection, strongly related to the presence of less common hrHPV genotypes, probably with a slower transforming power, but with a potential risk of progression if the infection persists. HPV DNA genotyping and follow‐up could be useful in these cases to verify if they are able to evolve into overt dysplastic changes and to improve knowledge of less common hrHPV genotypes