Monitoring is critical to assess management effectiveness, but broadscale systematic assessments of monitoring to evaluate and improve recovery efforts are lacking. We compiled 1808 time series from ...71 threatened and near‐threatened terrestrial and volant mammal species and subspecies in Australia (48% of all threatened mammal taxa) to compare relative trends of populations subject to different management strategies. We adapted the Living Planet Index to develop the Threatened Species Index for Australian Mammals and track aggregate trends for all sampled threatened mammal populations and for small (<35 g), medium (35–5500 g), and large mammals (>5500 g) from 2000 to 2017. Unmanaged populations (42 taxa) declined by 63% on average; unmanaged small mammals exhibited the greatest declines (96%). Populations of 17 taxa in havens (islands and fenced areas that excluded or eliminated introduced red foxes Vulpes vulpes and domestic cats Felis catus) increased by 680%. Outside havens, populations undergoing sustained predator baiting initially declined by 75% but subsequently increased to 47% of their abundance in 2000. At sites where predators were not excluded or baited but other actions (e.g., fire management, introduced herbivore control) occurred, populations of small and medium mammals declined faster, but large mammals declined more slowly, than unmanaged populations. Only 13% of taxa had data for both unmanaged and managed populations; index comparisons for this subset showed that taxa with populations increasing inside havens declined outside havens but taxa with populations subject to predator baiting outside havens declined more slowly than populations with no management and then increased, whereas unmanaged populations continued to decline. More comprehensive and improved monitoring (particularly encompassing poorly represented management actions and taxonomic groups like bats and small mammals) is required to understand whether and where management has worked. Improved implementation of management for threats other than predation is critical to recover Australia's threatened mammals.
Efectos de diferentes estrategias de manejo sobre las tendencias a largo plazo de los mamíferos amenazados y casi amenazados de Australia
Resumen
El monitoreo es fundamental para evaluar la efectividad del manejo, aunque faltan evaluaciones sistemáticas y a gran escala de este monitoreo para evaluar y mejorar los esfuerzos de recuperación. Compilamos 1,808 series temporales de 71 especies y subespecies de mamíferos terrestres y voladores amenazadas y casi amenazadas en Australia (48% de todos los taxones de mamíferos amenazados) para comparar las tendencias relativas de las poblaciones sujetas a diferentes estrategias de manejo. Adaptamos el Índice Planeta Vivo para desarrollar el Índice de Especies Amenazadas para los Mamíferos Australianos y así rastrear las tendencias agregadas de todas las poblaciones muestreadas de mamíferos amenazados y de los mamíferos pequeños (<35 g), medianos (35–5,500 g) y grandes (>5,500 g) entre 2000 y 2017. Las poblaciones sin manejo (42 taxones) declinaron en un 63% en promedio; los mamíferos pequeños sin manejo exhibieron las declinaciones más marcadas (96%). Las poblaciones de 17 taxones incrementaron 680% en los refugios (islas o áreas encercadas que excluían o eliminaban al zorro rojo Vulpes vulpes y al gato doméstico Felis catus, especies introducidas) Afuera de los refugios, las poblaciones sometidas al cebado constante de los depredadores en un inicio declinaron en un 75% pero después incrementaron al 47% de su abundancia para el 2000. En los sitios en donde los depredadores no fueron excluidos o cebados sino sometidos a otras acciones (manejo del fuego, control de herbívoros introducidos), las poblaciones de los mamíferos pequeños y medianos declinaron más rápido, pero los mamíferos grandes declinaron de manera más lenta que las poblaciones sin manejo. Sólo el 13% de los taxones contaron con datos para sus poblaciones con y sin manejo; las comparaciones entre índices para este subconjunto mostraron que los taxones con poblaciones en incremento dentro de los refugios declinaron afuera de éstos, pero los taxones con poblaciones sujetas al cebado de depredadores afuera de los refugios declinaron más lentamente que las poblaciones sin manejo y después incrementaron, mientras que las poblaciones sin manejo continuaron su declinación. Se requiere un monitoreo más completo y mejorado (particularmente el que engloba las acciones de manejo mal representadas y los grupos taxonómicos como los murciélagos y los mamíferos pequeños) para entender si ha funcionado el manejo y en dónde. La implementación mejorada del manejo para las amenazas distintas a la depredación es fundamental para recuperar a los mamíferos amenazados de Australia.
【摘要】
监测对于评估保护管理有效性至关重要, 但目前仍缺乏对监测的大尺度系统评估, 以评价和提高恢复工作。本研究整理了澳大利亚71种受威胁或近危的陆生及飞行野生哺乳动物物种和亚种(占所有受威胁哺乳动物的48%)的1808个时间序列, 以比较受到不同管理策略影响的种群的相对趋势。我们基于“地球生命力指数(Living Planet Index)”开发了“澳大利亚哺乳动物受威胁物种指数”, 并追踪了2000‐2017年所有采样的受威胁哺乳动物种群以及小型(<35克)、中型(35‐5500克)和大型哺乳动物(>5500克)的总体趋势。结果表明, 未受到管理的种群(42个类群)数量平均减少了63%;未受到管理的小型哺乳动物种群数量下降幅度最大(96%)。17个在避难所(驱除或消灭了外来赤狐Vulpes vulpe及家猫Felis catus的岛屿和围栏区)中生活的类群种群数量增加了680%。在避难所外, 受到持续捕食者诱捕管理的种群最初数量下降了75%, 但随后增加到2000年种群数量的47%。在没有驱除或诱捕捕食者, 但采取了其它行动(如火灾管理、引入食草动物控制)的位点, 小型和中型哺乳动物种群比没有受到管理的种群下降得更快, 但大型哺乳动物相比下降得更慢。只有13%的类群同时有未受到管理种群和受到管理种群的数据, 这部分数据的指数比较显示, 在避难所内种群增加的类群在避难所外种群有所下降, 但在避难所外受到捕食者诱捕的种群比没有管理的种群下降更慢且随后种群数量增加, 而未受到管理的种群则持续下降。未来还需要更全面和更好的监测工作(特别是纳入没有得到充分代表的管理行动及类群, 如蝙蝠和小型哺乳动物), 以了解管理的有效性以及有效的区域。进一步落实对捕食以外威胁的管理措施, 对于澳大利亚受威胁哺乳动物恢复至关重要。【翻译:胡怡思;审校:聂永刚】
The previously reported randomised controlled trial of a consensus regimen of pulse cyclophosphamide suggested that it was as effective as a daily oral (DO) cyclophosphamide for remission induction ...of antineutrophil cytoplasm autoantibodies-associated systemic vasculitis when both were combined with the same glucocorticoid protocol (CYCLOPS study (Randomised trial of daily oral versus pulse Cyclophosphamide as therapy for ANCA-associated Systemic Vasculitis published de groot K, harper L et al Ann Int Med 2009)). The study had limited power to detect a difference in relapse. This study describes the long-term outcomes of patients in the CYCLOPS study.
Long-term outcomes were ascertained retrospectively from 148 patients previously recruited to the CYCLOPS Trial. Data on survival, relapse, immunosuppressive treatment, cancer incidence, bone fractures, thromboembolic disease and cardiovascular morbidity were collected from physician records retrospectively. All patients were analysed according to the group to which they were randomised.
Median duration of follow-up was 4.3 years (IQR, 2.95-5.44 years). There was no difference in survival between the two limbs (p=0.92). Fifteen (20.8%) DO and 30 (39.5%) pulse patients had at least one relapse. The risk of relapse was significantly lower in the DO limb than the pulse limb (HR=0.50, 95% CI 0.26 to 0.93; p=0.029). Despite the increased risk of relapse in pulse-treated patients, there was no difference in renal function at study end (p=0.82). There were no differences in adverse events between the treatment limbs.
Pulse cyclophosphamide is associated with a higher relapse risk than DO cyclophosphamide. However, this is not associated with increased mortality or long-term morbidity. Although the study was retrospective, data was returned in 90% of patients from the original trial.
Biallelic mutations in ATM cause ataxia-telangiectasia (AT), a rare inherited disease with a high incidence of cancer. Precise estimates of the risk, presentation, and outcomes of cancer in patients ...with AT need to be addressed in large series.
In this large retrospective cohort, 69 patients with cancers (24.5%) were identified among 279 patients with AT. Centralized review was performed on 60% of the lymphomas. Incidence rates were compared with the French population, and risk factors were analyzed.
Eight patients developed acute leukemias (including four T-cell acute lymphoblastic leukemias), 12 developed Hodgkin lymphoma (HL), 38 developed non-Hodgkin lymphoma (NHL), three developed T-cell prolymphocytic leukemia (T-PLL), and eight developed carcinoma at a median age of 8.3, 10.6, 9.7, 24.2, and 31.4 years, respectively (P < .001). The majority of NHLs were aggressive B-cell NHL. Epstein-Barr virus was associated with all of the HLs and 50% of the NHLs. Overall survival was shorter in patients with AT who developed cancer compared with those who did not develop cancer (15 v 24 years, respectively; P < .001). Survival was improved in patients who achieved a major response to treatment (3.46 v 0.87 years for major v minor responses, respectively; P = .011). Immunodeficiency was associated with increased risk of cancer. ATM mutation type was associated with a difference in survival in the entire cohort but not with cancer incidence or cancer survival.
B-cell NHL, HL, and acute lymphoblastic leukemia occur at a high rate and earlier age than carcinomas in AT. T-PLLs are rarer than initially reported. Prognosis is poor, but patients may benefit from treatment with an improved survival.
Heterozygous germline
mutations strongly predispose to leukemia, immunodeficiency, and/or lymphoedema. We describe a series of 79 patients (53 families) diagnosed since 2011, made up of all patients ...in France and Belgium, with a follow up of 2249 patients/years. Median age at first clinical symptoms was 18.6 years (range, 0-61 years). Severe infectious diseases (mycobacteria, fungus, and human papilloma virus) and hematologic malignancies were the most common first manifestations. The probability of remaining symptom-free was 8% at 40 years old. Among the 53 probands, 24 had missense mutations including 4 recurrent alleles, 21 had nonsense or frameshift mutations, 4 had a whole-gene deletion, 2 had splice defects, and 2 patients had complex mutations. There were significantly more cases of leukemia in patients with missense mutations (n=14 of 34) than in patients with nonsense or frameshift mutations (n=2 of 28). We also identify new features of the disease: acute lymphoblastic leukemia, juvenile myelomonocytic leukemia, fatal progressive multifocal leukoencephalopathy related to the JC virus, and immune/inflammatory diseases. A revised International Prognostic Scoring System (IPSS) score allowed a distinction to be made between a stable disease and hematologic transformation. Chemotherapy is of limited efficacy, and has a high toxicity with severe infectious complications. As the mortality rate is high in our cohort (up to 35% at the age of 40), hematopoietic stem cell transplantation (HSCT) remains the best choice of treatment to avoid severe infectious and/or hematologic complications. The timing of HSCT remains difficult to determine, but the earlier it is performed, the better the outcome.
Allogeneic stem cell transplantation remains the only curative treatment for sickle cell anemia (SCA), but the place of myeloablative conditioning in the procedure remains to be defined. The aim of ...the present study was to analyze long-term outcomes, including chimerism, SCA-related events and biological data (hemoglobin, reticulocytes, HbS%), and fertility in a French series of 234 SCA patients under 30 years of age who, from 1988 to 2012, received a matched-sibling-donor stem cell transplantation following standardized myeloablative conditioning busulfan, cyclophosphamide and rabbit antithymocyte globulin (ATG). Since the first report of the series (1988-2004), 151 new consecutive patients with SCA have been similarly transplanted. Considering death, non-engraftment or rejection (donor cells <5%) as events, the 5-year event-free survival was 97.9% (95% confidence interval: 95.5-100%), confirming, since the year 2000, an at least 95% chance of cure. In the overall cohort (n=234, median follow up 7.9 years), event-free survival was not associated with age, but chronic-graft-
-host disease (cGvHD) was independently associated with recipient's age >15 years (hazard ratio=4.37;
=0.002) and lower (5-15
20 mg/kg) ATG dose (hazard ratio=4.55;
=0.001). At one year, 44% of patients had mixed chimerism (5-95% donor cells), but those prepared with ATG had no graft rejection. No events related to SCA occurred in patients with mixed chimerism, even those with 15-20% donor cells, but hemolytic anemia stigmata were observed with donor cells <50%. Myeloablative transplantation with matched-sibling donor currently has a higher event-free survival (98%) in patients under 30 years of age than that reported for non-myeloablative conditioning (88%). Nevertheless, the risk of cGvHD in older patients and the need to preserve fertility might be indications for a non-myeloablative conditioning.
Congenital neutropenias (CNs) are rare heterogeneous genetic disorders, with about 25% of patients without known genetic defects. Using whole-exome sequencing, we identified a heterozygous mutation ...in the SRP54 gene, encoding the signal recognition particle (SRP) 54 GTPase protein, in 3 sporadic cases and 1 autosomal dominant family. We subsequently sequenced the SRP54 gene in 66 probands from the French CN registry. In total, we identified 23 mutated cases (16 sporadic, 7 familial) with 7 distinct germ line SRP54 mutations including a recurrent in-frame deletion (Thr117del) in 14 cases. In nearly all patients, neutropenia was chronic and profound with promyelocytic maturation arrest, occurring within the first months of life, and required long-term granulocyte colony-stimulating factor therapy with a poor response. Neutropenia was sometimes associated with a severe neurodevelopmental delay (n = 5) and/or an exocrine pancreatic insufficiency requiring enzyme supplementation (n = 3). The SRP54 protein is a key component of the ribonucleoprotein complex that mediates the co-translational targeting of secretory and membrane proteins to the endoplasmic reticulum (ER). We showed that SRP54 was specifically upregulated during the in vitro granulocytic differentiation, and that SRP54 mutations or knockdown led to a drastically reduced proliferation of granulocytic cells associated with an enhanced P53-dependent apoptosis. Bone marrow examination of SRP54-mutated patients revealed a major dysgranulopoiesis and features of cellular ER stress and autophagy that were confirmed using SRP54-mutated primary cells and SRP54 knockdown cells. In conclusion, we characterized a pathological pathway, which represents the second most common cause of CN with maturation arrest in the French CN registry.
•Identification of SRP54 mutations in congenital neutropenia.•SRP54 mutations induce ER stress and autophagy associated with apoptosis.
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Global efforts to deliver internationally agreed goals to reduce carbon emissions, halt biodiversity loss, and retain essential ecosystem services have been poorly integrated. These goals rely in ...part on preserving natural (e.g., native, largely unmodified) and seminatural (e.g., low intensity or sustainable human use) forests, woodlands, and grasslands. To show how to unify these goals, we empirically derived spatially explicit, quantitative, area‐based targets for the retention of natural and seminatural (e.g., native) terrestrial vegetation worldwide. We used a 250‐m‐resolution map of natural and seminatural vegetation cover and, from this, selected areas identified under different international agreements as being important for achieving global biodiversity, carbon, soil, and water targets. At least 67 million km2 of Earth's terrestrial vegetation (∼79% of the area of vegetation remaining) required retention to contribute to biodiversity, climate, soil, and freshwater conservation objectives under 4 United Nations’ resolutions. This equates to retaining natural and seminatural vegetation across at least 50% of the total terrestrial (excluding Antarctica) surface of Earth. Retention efforts could contribute to multiple goals simultaneously, especially where natural and seminatural vegetation can be managed to achieve cobenefits for biodiversity, carbon storage, and ecosystem service provision. Such management can and should co‐occur and be driven by people who live in and rely on places where natural and sustainably managed vegetation remains in situ and must be complemented by restoration and appropriate management of more human‐modified environments if global goals are to be realized.
Retención de la vegetación natural para salvaguardar la biodiversidad y la humanidad
Resumen
Hoy en día hay muy poca integración de los esfuerzos mundiales para alcanzar los objetivos internacionales de reducción de las emisiones de carbono, impedimento de la pérdida de biodiversidad y conservación de los servicios ambientales esenciales. Estos objetivos dependen parcialmente de la conservación de los bosques, selvas y praderas naturales (por ejemplo, nativos y en su mayoría sin alteraciones) y seminaturales (por ejemplo, de uso humano sostenible o de baja intensidad). Obtuvimos de manera empírica objetivos espacialmente explícitos, cuantitativos y basados en áreas para la conservación de la vegetación terrestre natural y seminatural (por ejemplo, nativa) en todo el mundo para mostrar cómo unificar los objetivos internacionales. Usamos un mapa de 250 m de resolución de la cubierta vegetal natural y seminatural y, a partir de él, seleccionamos las áreas identificadas como importantes en diferentes acuerdos internacionales para alcanzar los objetivos globales de biodiversidad, carbono, suelo y agua. Al menos 67 millones de km2 de la vegetación terrestre de la Tierra (∼79% de la superficie de vegetación restante) requieren ser conservados para contribuir a los objetivos de conservación de la biodiversidad, el clima, el suelo y el agua dulce en virtud de cuatro de las resoluciones de las Naciones Unidas. Esto equivale a conservar la vegetación natural y seminatural en al menos el 50% de la superficie terrestre total de la Tierra (sin contar a la Antártida). Los esfuerzos de retención podrían contribuir a alcanzar múltiples objetivos simultáneamente, especialmente en donde la vegetación natural y seminatural puede gestionarse para lograr beneficios colaterales para la biodiversidad, el almacenamiento de carbono y la provisión de servicios ambientales. Esta gestión puede y debe ser impulsada y llevada a cabo por las personas que viven en y dependen de los lugares donde la vegetación natural y gestionada de forma sostenible permanece in situ y debe complementarse con la restauración y la gestión adecuada de entornos modificados por el hombre si se quieren alcanzar los objetivos globales.
【摘要】
在全球范围内, 为实现国际上制定的减少碳排放、阻止生物多样性丧失和保留必需生态系统服务的目标而付出努力一直没有得到很好的整合。这些目标部分依赖于保护自然 (如原生的、基本未经改造的) 和半自然 (如受到低强度或可持续性人类利用的) 森林、林地和草地。为了说明如何统一这些目标, 我们根据经验制定了空间上明确的、定量的、基于面积的目标, 以保留全球的自然和半自然 (如原生的) 陆地植被。本研究使用分辨率为 250 米的自然和半自然植被地图, 并从中选择了根据不同国际协议确定的对实现全球生物多样性、碳、土壤和水目标非常重要的地区。结果显示, 至少要保留地球上 6700 万平方公里的陆地植被 (约占剩余植被面积的 79%), 才能帮助实现联合国 4 项决议中的生物多样性、气候、土壤和淡水保护目标。这相当于在地球总的陆地表面 (不包括南极洲) 保留至少 50%的自然和半自然植被。保留植被可以同时促进多个目标的实现, 特别是在自然和半自然植被的管理有助于实现生物多样性、碳储量和提供生态系统服务的共同利益的情况下。要实现全球目标, 可以且应该同时采取管理措施, 并由生活在原地保留的自然植被及可持续管理植被中的人们来推动, 还必须补充对更多人类改造的环境的恢复和适当管理。【翻译: 胡怡思; 审校: 聂永刚】
Epstein-Barr virus (EBV) is an ubiquitous herpesvirus with a tropism for epithelial cells (where lytic replication occurs) and B-cells (where latency is maintained). EBV persists throughout life and ...chronic infection is asymptomatic in most individuals. However, immunocompromised patients may be unable to control EBV infection and are at increased risk of EBV-related malignancies, such as diffuse large B-cell lymphomas or Hodgkin's lymphomas. Ataxia telangiectasia (AT) is a primary immunodeficiency caused by mutations in the
gene and associated with an increased incidence of cancers, particularly EBV-associated lymphomas. However, the immune deficiency present in AT patients is often too modest to explain the increased incidence of EBV-related malignancies. The ATM defect in these patients could therefore impair the normal regulation of EBV latency in B-cells, thus promoting lymphomagenesis. This suggests that ATM plays a role in the normal regulation of EBV latency. ATM is a serine/threonine kinase involved in multiple cell functions such as DNA damage repair, cell cycle regulation, oxidative stress, and gene expression. ATM is implicated in the lytic cycle of EBV, where EBV uses the activation of DNA damage repair pathway to promote its own replication. ATM regulates the latent cycle of the EBV-related herpesvirus KSHV and MHV68. However, the contribution of ATM in the control of the latent cycle of EBV is not yet known. A better understanding of the regulation of EBV latency could be harnessed in the conception of novel therapeutic strategies in AT and more generally in all ATM deficient EBV-related malignancies.
Background Chronic granulomatous disease (CGD) is a rare phagocytic disorder that results in not only infections but also potentially severe inflammatory manifestations that can be difficult to ...diagnose and treat. Objective To describe inflammatory manifestations in a single-center cohort of patients with CGD. Methods Medical records of patients treated at Necker-Enfants Malades Hospital (Paris, France) between 1968 and 2009 and registered at the French National Reference Center for Primary Immunodeficiencies (CEREDIH) were retrospectively reviewed. Results In a study population of 98 patients, a total of 221 inflammatory episodes were recorded in 68 individuals (69.4%). The incidence rate of inflammatory episodes was 0.15 per person-year (0.18 in patients with X-linked XL CGD and 0.08 in patients with autosomal-recessive AR CGD). The most commonly affected organs were the gastrointestinal tract (in 88.2% of the patients), lungs (26.4%), the urogenital tract (17.6%), and eyes (8.8%). Inflammation at other sites (the skin, central nervous system, and tympanum) and autoimmune manifestations (lupus, arthritis, etc) were recorded in 19.1% and 10.3% of the patients, respectively. Granuloma was found in 50% of the 44 histological analyses reviewed. The risk of inflammatory episodes was 2-fold higher in patients with XL-CGD than in patients with AR-CGD (relative risk, 2.22; 95% CI, 1.43-3.46). Conclusions Patients with XL-CGD have a higher risk of developing inflammatory episodes than do patients with AR-CGD. Although the most commonly affected organ is the gastrointestinal tract, other sites can be involved, making the management of patients with CGD a complex, multidisciplinary task.
Raman spectroscopy is a vibrational technique which provides information about the chemical structure. Nevertheless, since many chemicals are present in a sample at very low concentration, the Raman ...signal observed is extremely weak. In surface enhanced Raman scattering (SERS), Raman signals can be enhanced by many orders of magnitude when nanoparticles are used. To the best of our knowledge, this is the first report in the breast cancer detection based on serum SERS. The serum samples were obtained from 12 patients who were clinically diagnosed with advanced breast cancer and 15 controls. In the same proportion, the serum samples were mixed with colloidal gold nanoparticles of 40 nm using sonication. At least 10 spectra were collected of each serum sample using a Jobin-Yvon LabRAM Raman Spectrometer with a laser of 830 nm. Raw spectra were processed by carrying baseline correction, smoothing, and normalization and then analyzed using principle component analysis (PCA) and linear discriminant analysis (LDA). Raman spectra showed strongly enhanced bands in the 600–1800 cm
−1
range due to the nanoparticle colloidal clusters observed. These Raman bands allowed identifying biomolecules present at low concentration as amide I and III,
β
carotene, glutathione, tryptophan, tyrosine, and phenylalanine. Preliminary results demonstrated that SERS and PCA-LDA can be used to discriminate between control and cancer samples with high sensitivity and specificity. SERS allowed short exposures and required a minimal sample preparation. The preliminary results suggest that SERS and PCA-LDA could be an excellent support technique for the breast cancer detection using serum samples.
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