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1.
BMJ Mil Health ; 2024 Jun 27.
Article in English | MEDLINE | ID: mdl-38942432

ABSTRACT

Soldiers must achieve high-level mission-preparedness to endure extended periods of physical and cognitive activity, with unpredictable recovery, in all environments. Nutrition provides the foundation for health and performance. Militaries have not maximised the strategic and financial value that considering nutrition as a military capability could deliver. A whole system approach to military nutrition, based on the prepare-perform-recover human capability cycle phases, is presented. Trainee nutrition requirements, through to very-high-readiness forces undertaking arduous roles at reach, must be specifically addressed. Promoting military performance diets in the prepare phase, through practitioner-supported nutrition education and food provision, will ensure mission readiness and mitigate ill health. Delivering nutrition in field settings in the perform phase-through smaller/lighter, nutritionally optimised rations and smart packaging technologies-will improve utility and minimise waste. Strategic dietary supplement use can provide a mission performance-enhancing adjunct to a food-first philosophy. Impact value chain analysis of military nutrition capability investments could support cost-benefit measurement.

2.
bioRxiv ; 2023 Nov 13.
Article in English | MEDLINE | ID: mdl-38014127

ABSTRACT

Behavioral interactions within the nuclear family may play a pivotal role in the emergence of autonomy and agency in mammals. While the emergence of a behavior may arise over weeks in line with nervous system maturation, individual events occur on sub-second time scales. This makes it uniquely challenging to track development in the lab where observations are made over minutes to hours or in ecological studies which lack individual specificity and sub-second precision. Here we study families of gerbils, a highly social rodent, raised in enlarged home-cage environments over weeks of development, using continuous video recordings to capture tens of millions of time points per family. Focusing on postnatal day 15 (when pups leave the nest) to day 30 (around the time when pups would disperse) we identify distinct developmental trajectories for both autonomous behaviors (exploration, food and water foraging), and social behaviors (huddling, approach, time spent together). Most of these behaviors emerge in concert with clear diurnal and crepuscular patterns and we find sex differences in both autonomous and social behaviors. Our work supports the emergence of distinct autonomous and social behavior phenotypes as the behavioral correlates of critical developmental periods of maturation of the rodent brain and can form the basis of future research on development from both neuroscience and behavioral biology perspectives.

3.
Integr Org Biol ; 5(1): obad001, 2023.
Article in English | MEDLINE | ID: mdl-36915395

ABSTRACT

Mormyridae is an early diverging family of Teleostean fishes that produce an electric field for navigation and communication using an electric organ. This clade has a diverse array of soft-tissue rostral appendages, such as the chin-swelling, the Schnauzenorgan, and the tubesnout combined with a Schnauzenorgan, that have evolved multiple times. Here we assess if macroscopically convergent, soft-tissue rostral appendages are also histologically convergent. Further, we investigate how the histology of these appendages can inform their function. We sampled independent gains of the chin-swelling and Schnauzenorgan to understand similarities and differences in their anatomies. We show that macroscopically convergent rostral appendages are also convergent at a histological level, and different types of rostral appendages share a similar anatomy; that said, minor differences likely relate to their specific functions. Based on a comparison of the skeletal muscle distribution and the differing attachment shapes of each appendage to the dentary, we conclude that the Schnauzenorgan is capable of a wider range of movements than the chin swelling. Furthermore, the anatomy suggests that these soft-tissue rostral appendages likely function as electrosensory foveas (i.e., an appendage that focuses a sensory system). Lastly, these histological data support the hypothesis that the chin swelling may be a precursor to the Schnauzenorgan.


ResumenMormyridae es una de las primeras familias divergentes de peces teleósteos que producen un campo eléctrico para la navegación y la comunicación mediante un órgano eléctrico. Este clado tiene una variedad diversa de apéndices rostrales de tejidos blandos, como el mentón hinchado, el Schnauzenorgan y el hocico tubular combinado con un Schnauzenorgan, que han evolucionado varias veces. Aquí evaluamos si los apéndices rostrales de tejido blando macroscópicamente convergentes también son histológicamente convergentes. Además, investigamos cómo la histología de estos apéndices puede informar sus funciones. Tomamos muestras de ganancias independientes del mentón hinchado y del Schnauzenorgan para comprender las similitudes y diferencias en sus anatomías. Mostramos que los apéndices rostrales macroscópicamente convergentes también lo son a nivel histológico, y diferentes tipos de apéndices rostrales comparten una anatomía similar; dicho esto, es probable que las diferencias menores se relacionen con sus funciones específicas. Con base en una comparación de la distribución del músculo esquelético y las diferentes formas de unión de cada apéndice al dentario, concluimos que el Schnauzenorgan es capaz de realizar una gama más amplia de movimientos que el mentón hinchado. Además, la anatomía sugiere que estos apéndices rostrales de tejido blando probablemente funcionen como fóveas electrosensoriales (es decir, un apéndice que enfoca un sistema sensorial). Por último, estos datos histológicos apoyan la hipótesis de que el mentón hinchado puede ser un precursor del Schnauzenorgan.

4.
Zootaxa ; 5094(1): 153-168, 2022 Feb 02.
Article in English | MEDLINE | ID: mdl-35391458

ABSTRACT

A survey of tarsonemid mites associated with plants of the family Myrtaceae was conducted in seven areas of the Atlantic Forest biome. Fourteen known species were registered; other 21 morphospecies was identified up to genus level. Additionally, a new species, Tarsonemus conduru Lofego Cavalcante sp. nov. is described based on specimens collected in the Atlantic Forest of Bahia state.


Subject(s)
Mites , Myrtaceae , Animals , Brazil , Forests
5.
Hernia ; 26(3): 865-871, 2022 06.
Article in English | MEDLINE | ID: mdl-35399142

ABSTRACT

PURPOSE: Physical therapy (PT) and rehabilitation are widely utilized in a variety of disease processes to improve function, return to activities of daily living (ADLs), and promote overall recovery. However, hernia repair has struggled to adopt this practice despite operations occurring in one of the most dynamic parts of the body - the abdominal core. This study sought to understand perspectives and perceived barriers regarding the incorporation of PT and rehabilitation in hernia care. METHODS: A standardized rehabilitation protocol was developed by the Abdominal Core Health Quality Collaborative (ACHQC), a national quality improvement initiative specific to hernia disease, and launched in 2019. Empiric data from the ACHQC was then obtained to describe preliminary utilization. A prospective electronic survey was then deployed to all surgeons participating in the ACHQC to aid in interpreting the identified trends. The survey included questions regarding the current use of PT in their practice, as well as further opinions on the functionality, benefit, and barriers to its use. RESULTS: We identified 1,544 patients who were listed as receiving some form of postoperative rehabilitation, of which 992 (64.2%) had a primary diagnosis of ventral hernia and 552 (35.8%) had an inguinal hernia. Among patients who had a ventral hernia, 863 (87.0%) received self-directed rehabilitation exercises compared to 488 (88.4%) of inguinal hernia patients. The subsequent survey exploring these trends was completed by 46 ACHQC surgeons (10.2%). More than half (52%) reported using PT for hernia patients, primarily in abdominal wall reconstruction cases (92%). Of those who did not report using PT, 50% cited unknown clinical benefit and another 27% cited unknown PT resources. PT utilization was typically concentrated to the postoperative period (58%), while 42% reported also using it preoperatively. Despite 72% of respondents citing a perceived benefit of PT in hernia patients, overall use of PT was primarily reported as 'occasional' by 42%, with another 27% reporting 'rarely.' Perceived benefits of PT included increased core strength, stability, mobility, patient satisfaction, education, independence, earlier return to work and ADLs, overall improved recovery, and decreased risk of postoperative issues. Reported barriers to implementing PT in practice or adapting the ACHQC Rehabilitation Protocol included lack of education, lack of evidence of clinical benefit, and difficulties operationalizing the protocol. CONCLUSION: A national survey of hernia surgeons demonstrated willingness to adopt PT and rehabilitation protocols in their clinical practices and noted a high perceived benefit to patients. However, lack of education and evidence regarding the protocol may represent important barriers to overcome in widely disseminating these resources to patients. These gaps can be addressed through dedicated educational venues and additional studies establishing PT and rehabilitation as critical future adjuncts for the recovery of hernia repair patients.


Subject(s)
Hernia, Inguinal , Hernia, Ventral , Activities of Daily Living , Hernia, Inguinal/surgery , Hernia, Ventral/surgery , Herniorrhaphy/methods , Humans , Physical Therapy Modalities , Preliminary Data , Prospective Studies , Standard of Care
6.
An Acad Bras Cienc ; 93(suppl 3): e20200729, 2021.
Article in English | MEDLINE | ID: mdl-34431863

ABSTRACT

The aim of the present study was to conduct a survey of mites of the family Phytoseiidae associated with plants of the natural vegetation and cultivated forests in sites of three biomes (Amazon Forest, Cerrado and Pantanal) in the Mato Grosso State. Twenty-one species of 11 genera, of the three phytoseiid subfamilies were registered. Amblyseius Berlese was the most diverse genus, with five species. Iphiseiodes zuluagai Denmark & Muma was the most common species, collected from 12 plant species in five collection sites. Eleven phytoseiid species were reported for the first time in the Mato Grosso State.


Subject(s)
Mites , Animals , Brazil , Ecosystem , Forests
7.
Insects ; 12(1)2021 Jan 09.
Article in English | MEDLINE | ID: mdl-33435312

ABSTRACT

Although monitoring insect pest populations in the fields is essential in crop management, it is still a laborious and sometimes ineffective process. Imprecise decision-making in an integrated pest management program may lead to ineffective control in infested areas or the excessive use of insecticides. In addition, high infestation levels may diminish the photosynthetic activity of soybean, reducing their development and yield. Therefore, we proposed that levels of infested soybean areas could be identified and classified in a field using hyperspectral proximal sensing. Thus, the goals of this study were to investigate and discriminate the reflectance characteristics of soybean non-infested and infested with Bemisia tabaci using hyperspectral sensing data. Therefore, cages were placed over soybean plants in a commercial field and artificial whitefly infestations were created. Later, samples of infested and non-infested soybean leaves were collected and transported to the laboratory to obtain the hyperspectral curves. The results allowed us to discriminate the different levels of infestation and to separate healthy from whitefly infested soybean leaves based on their reflectance. In conclusion, these results show that hyperspectral sensing can potentially be used to monitor whitefly populations in soybean fields.

9.
Philos Trans A Math Phys Eng Sci ; 379(2189): 20200005, 2021 Jan 25.
Article in English | MEDLINE | ID: mdl-33280565

ABSTRACT

A European consortium of 15 laboratories across nine nations have worked together under the EUROFusion Enabling Research grants for the past decade with three principle objectives. These are: (a) investigating obstacles to ignition on megaJoule-class laser facilities; (b) investigating novel alternative approaches to ignition, including basic studies for fast ignition (both electron and ion-driven), auxiliary heating, shock ignition, etc.; and (c) developing technologies that will be required in the future for a fusion reactor. A brief overview of these activities, presented here, along with new calculations relates the concept of auxiliary heating of inertial fusion targets, and provides possible future directions of research and development for the updated European Roadmap that is due at the end of 2020. This article is part of a discussion meeting issue 'Prospects for high gain inertial fusion energy (part 2)'.

10.
Zootaxa ; 4868(4): zootaxa.4868.4.7, 2020 Oct 29.
Article in English | MEDLINE | ID: mdl-33311384

ABSTRACT

This paper announces a database on the taxonomy, distribution and host plants of mites of the family Tenuipalpidae Berlese (Acari: Tetranychoidea), available online at https://www.tenuipalpidae.ibilce.unesp.br/. In the Tenuipalpidae Database the recorded world distribution and range of host plants are provided for each tenuipalpid species, including synonyms, with a list of all relevant publications.


Subject(s)
Mites , Animals , Databases, Factual , Family , Plants
11.
AJNR Am J Neuroradiol ; 41(11): 2017-2019, 2020 11.
Article in English | MEDLINE | ID: mdl-32819898

ABSTRACT

Multisystem inflammatory syndrome in children is a recently described complication in the late phase of Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) infection involving systemic hyperinflammation and multiorgan dysfunction. The extent of its clinical picture is actively evolving and has yet to be fully elucidated. While neurologic manifestations of SARS-CoV-2 are well-described in the adult population, reports of neurologic complications in pediatric patients with SARS-CoV-2 infection are limited. We present a pediatric patient with SARS-CoV-2 infection with development of multisystem inflammatory syndrome and acute encephalopathy causing delirium who was found to have a cytotoxic lesion of the corpus callosum on neuroimaging. Cytotoxic lesions of the corpus callosum are a well-known, typically reversible entity that can occur in a wide range of conditions, including infection, seizure, toxins, nutritional deficiencies, and Kawasaki disease. We hypothesized that the cytotoxic lesion of the corpus callosum, in the index case, was secondary to the systemic inflammation from SARS-CoV-2 infection, resulting in multisystem inflammatory syndrome in children.


Subject(s)
Coronavirus Infections/complications , Corpus Callosum/pathology , Pneumonia, Viral/complications , Systemic Inflammatory Response Syndrome/pathology , Adolescent , Betacoronavirus , COVID-19 , Female , Humans , Pandemics , SARS-CoV-2
12.
J Drugs Dermatol ; 19(6): 625-631, 2020 Jun 01.
Article in English | MEDLINE | ID: mdl-32574009

ABSTRACT

OBJECTIVE: The goal of this 12 week, double-blinded, controlled, clinical study was to compare the efficacy, tolerability, and consumer acceptance of three novel retinol serums to tretinoin. METHOD: Forty-five photoaged females ages 35-65, Fitzpatrick skin types I-IV, with moderate wrinkling were enrolled in the 12-week study. A step-up protocol for increasing the dose of retinol serum (0.25%, 0.5%, 1.0%) or tretinoin cream (0.025%, 0.05%, and 0.1%) in combination with a test moisturizer or currently marketed dermatologist-recommended moisturizing cream was used. Overall severity of investigator graded photodamage, subject assessed photodamage, and tolerability criteria were evaluated using a 5-point ordinal scale at weeks 4, 8, and 12. Facial photography occurred at each visit and TEWL was measured at baseline and week 12. Histologic evaluation of punch biopsies was completed on baseline and week 12 samples. RESULTS: After 12 weeks of use, both retinol serum and tretinoin demonstrated parity across investigator and subject assessment measurements as well as diagnostic measures including TEWL. Retinol serum subjects showed significant week 4 improvement in visual skin smoothness compared to tretinoin subjects (P=0.031). There was highly significant improvement in skin dryness with the retinol serum (P<0.001) not seen in the tretinoin group. Histologic analysis of baseline and 12-week punch biopsies demonstrated newly formed collagen and greater epidermal thickening in retinol serum subjects compared to tretinoin treated subjects. CONCLUSION: Retinol serum (0.25%, 0.5%, 1.0%) was safe and effective with equivalent/or better performance and tolerability than tretinoin creams. J Drugs Dermatol. 2020;19(6): doi:10.36849/JDD.2020.5085.


Subject(s)
Facial Dermatoses/drug therapy , Skin Aging , Tretinoin/therapeutic use , Vitamin A/therapeutic use , Administration, Cutaneous , Adult , Aged , Dose-Response Relationship, Drug , Double-Blind Method , Facial Dermatoses/pathology , Female , Humans , Middle Aged , Serum , Skin Cream , Treatment Outcome , Tretinoin/administration & dosage , Vitamin A/administration & dosage
13.
Front Mol Biosci ; 7: 82, 2020.
Article in English | MEDLINE | ID: mdl-32435656

ABSTRACT

Lysosomal storage diseases (LSDs) are a family of 70 metabolic disorders characterized by mutations in lysosomal proteins that lead to storage material accumulation, multiple-organ pathologies that often involve neurodegeneration, and early mortality in a significant number of patients. Along with the necessity for more effective therapies, there exists an unmet need for further understanding of disease etiology, which could uncover novel pathways and drug targets. Over the past few decades, the growth in knowledge of disease-associated pathways has been facilitated by studies in model organisms, as advancements in mutagenesis techniques markedly improved the efficiency of model generation in mammalian and non-mammalian systems. In this review we highlight non-mammalian models of LSDs, focusing specifically on the zebrafish, a vertebrate model organism that shares remarkable genetic and metabolic similarities with mammals while also conferring unique advantages such as optical transparency and amenability toward high-throughput applications. We examine published zebrafish LSD models and their reported phenotypes, address organism-specific advantages and limitations, and discuss recent technological innovations that could provide potential solutions.

14.
Nat Commun ; 11(1): 1533, 2020 03 24.
Article in English | MEDLINE | ID: mdl-32210228

ABSTRACT

Phenotypic heterogeneity exists within collectively invading packs of tumor cells, suggesting that cellular subtypes cooperate to drive invasion and metastasis. Here, we take a chemical biology approach to probe cell:cell cooperation within the collective invasion pack. These data reveal metabolic heterogeneity within invasive chains, in which leader cells preferentially utilize mitochondrial respiration and trailing follower cells rely on elevated glucose uptake. We define a pyruvate dehydrogenase (PDH) dependency in leader cells that can be therapeutically exploited with the mitochondria-targeting compound alexidine dihydrochloride. In contrast, follower cells highly express glucose transporter 1 (GLUT1), which sustains an elevated level of glucose uptake required to maintain proliferation. Co-targeting of both leader and follower cells with PDH and GLUT1 inhibitors, respectively, inhibits cell growth and collective invasion. Taken together, our work reveals metabolic heterogeneity within the lung cancer collective invasion pack and provides rationale for co-targeting PDH and GLUT1 to inhibit collective invasion.


Subject(s)
Cell Movement/drug effects , Glucose Transporter Type 1/metabolism , Lung Neoplasms/pathology , Pyruvate Dehydrogenase (Lipoamide)/metabolism , Animals , Cell Communication/drug effects , Cell Line, Tumor , Cell Proliferation , Gene Knockdown Techniques , Glucose/metabolism , Glucose Transporter Type 1/antagonists & inhibitors , Glucose Transporter Type 1/genetics , Humans , Lung Neoplasms/drug therapy , Mice , Neoplasm Invasiveness/pathology , Neoplasm Invasiveness/prevention & control , Oxidative Phosphorylation , Pyruvate Dehydrogenase (Lipoamide)/antagonists & inhibitors , Pyruvate Dehydrogenase (Lipoamide)/genetics , RNA, Small Interfering/metabolism , Spheroids, Cellular
15.
Ann Oncol ; 31(3): 404-411, 2020 03.
Article in English | MEDLINE | ID: mdl-32067682

ABSTRACT

BACKGROUND: Immune checkpoint inhibitors (ICIs) are standard therapies for patients with advanced non-small-cell lung cancer (NSCLC) and a programmed death-ligand 1 (PD-L1) tumor proportion score (TPS) ≥50%. Tumor mutation burden (TMB) also predicts response to ICIs but is often not available in real time for decision making in the first-line setting. Smoking exposure can be a proxy for TMB in NSCLC. The impact of smoking status on efficacy of PD-1 blockade in NSCLC patients with PD-L1 TPS ≥50% has not been well defined. PATIENTS AND METHODS: To investigate the relationship between smoking and activity of ICIs in NSCLC, we retrospectively studied 315 patients with NSCLC and PD-L1 TPS ≥50% at five USA academic medical centers. Objective response rates (ORRs), progression-free survival (PFS), and duration of response (DOR) were compared between never (<100 lifetime cigarettes), light (≤10 pack-years), and heavy (>10 pack-years) smokers. A subset of patients underwent next-generation sequencing to estimate TMB. RESULTS: We identified 36 (11%) never, 42 (13%) light, and 237 (75%) heavy smokers with NSCLC and PD-L1 TPS ≥50% treated with ICIs. Objective responses were observed in 27%, 40%, and 40% of never, light, and heavy smokers, respectively (P = 0.180 never versus heavy; P = 1.000 light versus heavy). Median PFS and median DOR were numerically shorter in never and light smokers compared with heavy smokers (PFS 3.0 versus 4.0 versus 5.4 months; median DOR 6.9 versus 10.8 versus 17.8 months), but were not statistically different [PFS: hazard ratio (HR) 1.37, P = 0.135 and HR 1.24, P = 0.272; DOR: HR 1.92, P = 0.217 and HR 1.79, P = 0.141]. CONCLUSIONS: PD-(L)1 inhibitors are associated with antitumor activity in NSCLC with PD-L1 TPS ≥50% regardless of smoking status. Nevertheless, there is a signal of potentially decreased durability among never and light smokers that should be further evaluated. Distinct immunobiologic features may affect initial response versus durability of antitumor immunity to programmed cell death 1 (PD-1) blockade.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Phospholipase D/metabolism , Apoptosis , B7-H1 Antigen/genetics , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/genetics , Humans , Lung Neoplasms/drug therapy , Lung Neoplasms/genetics , Programmed Cell Death 1 Receptor , Retrospective Studies , Smokers
17.
Sci Adv ; 5(12): eaax2388, 2019 12.
Article in English | MEDLINE | ID: mdl-31844662

ABSTRACT

The causal association of Zika virus (ZIKV) with microcephaly, congenital malformations in infants, and Guillain-Barré syndrome in adults highlights the need for effective vaccines. Thus far, efforts to develop ZIKV vaccines have focused on the viral envelope. ZIKV NS1 as a vaccine immunogen has not been fully explored, although it can circumvent the risk of antibody-dependent enhancement of ZIKV infection, associated with envelope antibodies. Here, we describe a novel DNA vaccine encoding a secreted ZIKV NS1, that confers rapid protection from systemic ZIKV infection in immunocompetent mice. We identify novel NS1 T cell epitopes in vivo and show that functional NS1-specific T cell responses are critical for protection against ZIKV infection. We demonstrate that vaccine-induced anti-NS1 antibodies fail to confer protection in the absence of a functional T cell response. This highlights the importance of using NS1 as a target for T cell-based ZIKV vaccines.


Subject(s)
Epitopes/immunology , Vaccines, DNA/immunology , Viral Nonstructural Proteins/immunology , Zika Virus Infection/immunology , Animals , DNA/genetics , DNA/immunology , Disease Models, Animal , Guillain-Barre Syndrome/genetics , Guillain-Barre Syndrome/immunology , Guillain-Barre Syndrome/virology , Humans , Mice , T-Lymphocytes/immunology , T-Lymphocytes/virology , Viral Nonstructural Proteins/genetics , Zika Virus/immunology , Zika Virus/pathogenicity , Zika Virus Infection/prevention & control , Zika Virus Infection/virology
18.
Neuroscience ; 421: 162-175, 2019 11 21.
Article in English | MEDLINE | ID: mdl-31682818

ABSTRACT

Group III/IV striated muscle afferents are small diameter sensory neurons that play important roles in reflexes and sensation. To date, the morphological features of physiologically characterised group III/IV muscular afferents have not been identified. Here, the electrophysiological and morphological characteristics of sensory neurons innervating striated muscles of the mouse abdominal wall were investigated, ex vivo. Extracellular recordings were made from subcostal nerve trunks innervating the muscles. A distinctive class of mechanosensitive afferents was identified by a combination of physiological features including sensitivity to local compression, saturating response to graded stretch and, in most cases, absence of spontaneous firing. Studies were restricted to these distinctive units. These units had conduction velocities averaging 14 ±â€¯4 m/s (range: 8-20 m/s, n = 7); within the range of group III fibres in mice. Von Frey hairs were used to map receptive fields, which covered an area of 0.36 ±â€¯0.18 mm2 (n = 7). In 7 preparations, biotinamide filling of recorded nerve trunks revealed a single axon in the marked receptive field, with distinctive axonal branching and terminations meandering through the connective tissue sandwiched between two closely associated muscle layers. These axons were not immunoreactive for CGRP (n = 7) and were not activated by application of capsaicin (1 µM, n = 14). All of these afferents were strongly activated by a "metabolite mix" containing lactate, adenosine triphosphate and reduced pH. Responses to mechanical stimuli and to metabolites were additive. We have characterised a distinctive class of mechano- and chemo-sensitive group III afferent endings associated with connective tissue close to muscle fibres.


Subject(s)
Abdominal Muscles/innervation , Mechanoreceptors/physiology , Neurons, Afferent/physiology , Sensory Receptor Cells/physiology , Abdominal Muscles/physiology , Animals , Axons/metabolism , Axons/physiology , Capsaicin/pharmacology , Mice , Mice, Inbred C57BL , Muscle, Skeletal , Neural Conduction/physiology , Physical Stimulation , Sensory Thresholds/physiology
19.
Sci Adv ; 5(10): eaay5478, 2019 10.
Article in English | MEDLINE | ID: mdl-31616796

ABSTRACT

Pakistan and India may have 400 to 500 nuclear weapons by 2025 with yields from tested 12- to 45-kt values to a few hundred kilotons. If India uses 100 strategic weapons to attack urban centers and Pakistan uses 150, fatalities could reach 50 to 125 million people, and nuclear-ignited fires could release 16 to 36 Tg of black carbon in smoke, depending on yield. The smoke will rise into the upper troposphere, be self-lofted into the stratosphere, and spread globally within weeks. Surface sunlight will decline by 20 to 35%, cooling the global surface by 2° to 5°C and reducing precipitation by 15 to 30%, with larger regional impacts. Recovery takes more than 10 years. Net primary productivity declines 15 to 30% on land and 5 to 15% in oceans threatening mass starvation and additional worldwide collateral fatalities.

20.
Ann Oncol ; 30(10): 1653-1659, 2019 10 01.
Article in English | MEDLINE | ID: mdl-31435660

ABSTRACT

BACKGROUND: In non-small-cell lung cancers with programmed death-ligand 1 (PD-L1) expression on ≥50% of tumor cells, first-line treatment with the PD-1 inhibitor pembrolizumab improves survival compared with platinum-doublet chemotherapy. Whether higher PD-L1 levels within the expression range of 50%-100% predict for even greater benefit to pembrolizumab is currently unknown. PATIENTS AND METHODS: In this multicenter retrospective analysis, we analyzed the impact of PD-L1 expression levels on the overall response rate (ORR), median progression-free survival (mPFS), and median overall survival (mOS) in patients who received commercial pembrolizumab as first-line treatment of non-small-cell lung cancer (NSCLC) with a PD-L1 expression of ≥50% and negative for genomic alterations in the EGFR and ALK genes . RESULTS: Among 187 patients included in this analysis, the ORR was 44.4% [95% confidence interval (CI) 37.1% to 51.8%], the mPFS was 6.5 months (95% CI 4.5-8.5), and the mOS was not reached. The median PD-L1 expression level among patients who experienced a response to pembrolizumab was significantly higher than among patients with stable or progressive disease (90% versus 75%, P < 0.001). Compared with patients with PD-L1 expression of 50%-89% (N = 107), patients with an expression level of 90%-100% (N = 80) had a significantly higher ORR (60.0% versus 32.7%, P < 0.001), a significantly longer mPFS [14.5 versus 4.1 months, hazard ratio (HR) 0.50 (95% CI 0.33-0.74), P < 0.01], and a significantly longer mOS [not reached versus 15.9 months, HR 0.39 (95% CI 0.21-0.70), P = 0.002]. CONCLUSION: Among patients with NSCLC and PD-L1 expression of ≥50% treated with first-line pembrolizumab, clinical outcomes are significantly improved in NSCLCs with a PD-L1 expression of ≥90%. These findings have implications for treatment selection as well as for clinical trial interpretation and design.


Subject(s)
Adenocarcinoma of Lung/mortality , Antibodies, Monoclonal, Humanized/therapeutic use , Antineoplastic Agents, Immunological/therapeutic use , B7-H1 Antigen/metabolism , Carcinoma, Non-Small-Cell Lung/mortality , Carcinoma, Squamous Cell/mortality , Lung Neoplasms/mortality , Adenocarcinoma of Lung/drug therapy , Adenocarcinoma of Lung/immunology , Adenocarcinoma of Lung/pathology , Adult , Aged , Aged, 80 and over , B7-H1 Antigen/antagonists & inhibitors , Biomarkers, Tumor/immunology , Biomarkers, Tumor/metabolism , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/immunology , Carcinoma, Non-Small-Cell Lung/pathology , Carcinoma, Squamous Cell/drug therapy , Carcinoma, Squamous Cell/immunology , Carcinoma, Squamous Cell/pathology , Female , Follow-Up Studies , Humans , Lung Neoplasms/drug therapy , Lung Neoplasms/immunology , Lung Neoplasms/pathology , Male , Middle Aged , Patient Selection , Prognosis , Retrospective Studies , Survival Rate
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