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If human population growth is not controlled, natural areas must be sacrificed. An alternative is to create more habitat, terraforming Mars. However, this requires establishment of essential, ecosystem services on a planet currently unamenable to Terran species. Shorter term, assembling Terran-type ecosystems within contained environments is conceivable if mutually supportive species complements are determined. Accepting this, an assemblage of organisms that might form an early, forest environment is proposed, with rationale for its selection. A case is made for developing a contained facsimile, old growth forest on Mars, providing an oasis, proffering vital ecosystem functions (a forest bubble). It would serve as an extraterrestrial nature reserve (ETNR), psychological refuge and utilitarian botanic garden, supporting species of value to colonists for secondary metabolites (vitamins, flavours, perfumes, medicines, colours and mood enhancers). The design presented includes organisms that might tolerate local environmental variance and be assembled into a novel, bioregenerative forest ecosystem. This would differ from Earthly forests due to potential impact of local abiotic parameters on ecosystem functions, but it is argued that biotic support for space travel and colonization requires such developments. Consideration of the necessary species complement of an ETNR supports a view that it is not humanity alone that is reaching out to space, it is life, with all its diverse capabilities for colonization and establishment. Humans cannot, and will not, explore space alone because they did not evolve in isolation, being shaped over aeons by other species. Space will be travelled by a mutually supportive system of Terran organisms amongst which humans fit, exchanging metabolites and products of photosynthesis as they have always done.
Severe acute respiratory coronavirus virus 2 (SARS-CoV-2) transmissions among healthcare workers and hospitalized patients are challenging to confirm. Investigation of infected persons often reveals multiple potential risk factors for viral acquisition. We combined exposure investigation with genomic analysis confirming 2 hospital-based clusters. Prolonged close contact with unmasked, unrecognized infectious, individuals was a common risk.
Studying phenotypic and genetic characteristics of age at onset (AAO) and polarity at onset (PAO) in bipolar disorder can provide new insights into disease pathology and facilitate the development of screening tools.
To examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics.
Genome-wide association studies (GWASs) and polygenic score (PGS) analyses of AAO (n = 12 977) and PAO (n = 6773) were conducted in patients with bipolar disorder from 34 cohorts and a replication sample (n = 2237). The association of onset with disease characteristics was investigated in two of these cohorts.
Earlier AAO was associated with a higher probability of psychotic symptoms, suicidality, lower educational attainment, not living together and fewer episodes. Depressive onset correlated with suicidality and manic onset correlated with delusions and manic episodes. Systematic differences in AAO between cohorts and continents of origin were observed. This was also reflected in single-nucleotide variant-based heritability estimates, with higher heritabilities for stricter onset definitions. Increased PGS for autism spectrum disorder (β = −0.34 years, s.e. = 0.08), major depression (β = −0.34 years, s.e. = 0.08), schizophrenia (β = −0.39 years, s.e. = 0.08), and educational attainment (β = −0.31 years, s.e. = 0.08) were associated with an earlier AAO. The AAO GWAS identified one significant locus, but this finding did not replicate. Neither GWAS nor PGS analyses yielded significant associations with PAO.
AAO and PAO are associated with indicators of bipolar disorder severity. Individuals with an earlier onset show an increased polygenic liability for a broad spectrum of psychiatric traits. Systematic differences in AAO across cohorts, continents and phenotype definitions introduce significant heterogeneity, affecting analyses.
The first demonstration of laser action in ruby was made in 1960 by T. H. Maiman of Hughes Research Laboratories, USA. Many laboratories worldwide began the search for lasers using different materials, operating at different wavelengths. In the UK, academia, industry and the central laboratories took up the challenge from the earliest days to develop these systems for a broad range of applications. This historical review looks at the contribution the UK has made to the advancement of the technology, the development of systems and components and their exploitation over the last 60 years.
The criteria for objective memory impairment in mild cognitive impairment (MCI) are vaguely defined. Aggregating the number of abnormal memory scores (NAMS) is one way to operationalise memory impairment, which we hypothesised would predict progression to Alzheimer’s disease (AD) dementia.
As part of the Australian Imaging, Biomarkers and Lifestyle Flagship Study of Ageing, 896 older adults who did not have dementia were administered a psychometric battery including three neuropsychological tests of memory, yielding 10 indices of memory. We calculated the number of memory scores corresponding to z ≤ −1.5 (i.e., NAMS) for each participant. Incident diagnosis of AD dementia was established by consensus of an expert panel after 3 years.
Of the 722 (80.6%) participants who were followed up, 54 (7.5%) developed AD dementia. There was a strong correlation between NAMS and probability of developing AD dementia (r = .91, p = .0003). Each abnormal memory score conferred an additional 9.8% risk of progressing to AD dementia. The area under the receiver operating characteristic curve for NAMS was 0.87 [95% confidence interval (CI) .81–.93, p < .01]. The odds ratio for NAMS was 1.67 (95% CI 1.40–2.01, p < .01) after correcting for age, sex, education, estimated intelligence quotient, subjective memory complaint, Mini-Mental State Exam (MMSE) score and apolipoprotein E ϵ4 status.
Aggregation of abnormal memory scores may be a useful way of operationalising objective memory impairment, predicting incident AD dementia and providing prognostic stratification for individuals with MCI.
Objective: To investigate the effects of methylphenidate on long-term executive and neuropsychological functioning in children with attention problems following TBI, as well as the relationship between methylphenidate associated changes in lab-based neuropsychological measures of attentional control, processing speed, and executive functioning and parent- or self-report measures of everyday executive functioning. Method: 26 children aged 6–17 years, who were hospitalized for moderate-to-severe blunt head trauma 6 or more months previously, were recruited from a large children’s hospital medical center. Participants were randomized into a double-masked, placebo-controlled cross-over clinical trial. Participants completed a comprehensive neuropsychological battery and parent- and self-report ratings of everyday executive functioning at baseline, and at 4 weeks and 8 weeks following upward titration of medication to an optimal dose or while administered a placebo. Results: Methylphenidate was associated with significant improvements in processing speed, sustained attention, and both lab-based and everyday executive functioning. Significant treatment-by-period interactions were found on a task of sustained attention. Participants who were randomized to the methylphenidate condition for the first treatment period demonstrated random or erratic responding, with slower and more variable response times when given placebo during the second period. Conclusion: Results indicate that methylphenidate treatment is associated with positive outcomes in processing speed, sustained attention, and both lab-based and everyday measures of executive functioning compared to placebo group. Additionally, results suggest sustained attention worsens when discontinuing medication. (JINS, 2019, 25, 740–749)
BACKGROUND: IGTS is a rare phenomenon of paradoxical germ cell tumor (GCT) growth during or following treatment despite normalization of tumor markers. We sought to evaluate the frequency, clinical characteristics and outcome of IGTS in patients in 21 North-American and Australian institutions. METHODS: Patients with IGTS diagnosed from 2000-2017 were retrospectively evaluated. RESULTS: Out of 739 GCT diagnoses, IGTS was identified in 33 patients (4.5%). IGTS occurred in 9/191 (4.7%) mixed-malignant GCTs, 4/22 (18.2%) immature teratomas (ITs), 3/472 (0.6%) germinomas/germinomas with mature teratoma, and in 17 secreting non-biopsied tumours. Median age at GCT diagnosis was 10.9 years (range 1.8-19.4). Male gender (84%) and pineal location (88%) predominated. Of 27 patients with elevated markers, median serum AFP and Beta-HCG were 70 ng/mL (range 9.2-932) and 44 IU/L (range 4.2-493), respectively. IGTS occurred at a median time of 2 months (range 0.5-32) from diagnosis, during chemotherapy in 85%, radiation in 3%, and after treatment completion in 12%. Surgical resection was attempted in all, leading to gross total resection in 76%. Most patients (79%) resumed GCT chemotherapy/radiation after surgery. At a median follow-up of 5.3 years (range 0.3-12), all but 2 patients are alive (1 succumbed to progressive disease, 1 to malignant transformation of GCT). CONCLUSION: IGTS occurred in less than 5% of patients with GCT and most commonly after initiation of chemotherapy. IGTS was more common in patients with IT-only on biopsy than with mixed-malignant GCT. Surgical resection is a principal treatment modality. Survival outcomes for patients who developed IGTS are favourable.
Different diagnostic interviews are used as reference standards for major depression classification in research. Semi-structured interviews involve clinical judgement, whereas fully structured interviews are completely scripted. The Mini International Neuropsychiatric Interview (MINI), a brief fully structured interview, is also sometimes used. It is not known whether interview method is associated with probability of major depression classification.
To evaluate the association between interview method and odds of major depression classification, controlling for depressive symptom scores and participant characteristics.
Data collected for an individual participant data meta-analysis of Patient Health Questionnaire-9 (PHQ-9) diagnostic accuracy were analysed and binomial generalised linear mixed models were fit.
A total of 17 158 participants (2287 with major depression) from 57 primary studies were analysed. Among fully structured interviews, odds of major depression were higher for the MINI compared with the Composite International Diagnostic Interview (CIDI) (odds ratio (OR) = 2.10; 95% CI = 1.15–3.87). Compared with semi-structured interviews, fully structured interviews (MINI excluded) were non-significantly more likely to classify participants with low-level depressive symptoms (PHQ-9 scores ≤6) as having major depression (OR = 3.13; 95% CI = 0.98–10.00), similarly likely for moderate-level symptoms (PHQ-9 scores 7–15) (OR = 0.96; 95% CI = 0.56–1.66) and significantly less likely for high-level symptoms (PHQ-9 scores ≥16) (OR = 0.50; 95% CI = 0.26–0.97).
The MINI may identify more people as depressed than the CIDI, and semi-structured and fully structured interviews may not be interchangeable methods, but these results should be replicated.
Declaration of interest
Drs Jetté and Patten declare that they received a grant, outside the submitted work, from the Hotchkiss Brain Institute, which was jointly funded by the Institute and Pfizer. Pfizer was the original sponsor of the development of the PHQ-9, which is now in the public domain. Dr Chan is a steering committee member or consultant of Astra Zeneca, Bayer, Lilly, MSD and Pfizer. She has received sponsorships and honorarium for giving lectures and providing consultancy and her affiliated institution has received research grants from these companies. Dr Hegerl declares that within the past 3 years, he was an advisory board member for Lundbeck, Servier and Otsuka Pharma; a consultant for Bayer Pharma; and a speaker for Medice Arzneimittel, Novartis, and Roche Pharma, all outside the submitted work. Dr Inagaki declares that he has received grants from Novartis Pharma, lecture fees from Pfizer, Mochida, Shionogi, Sumitomo Dainippon Pharma, Daiichi-Sankyo, Meiji Seika and Takeda, and royalties from Nippon Hyoron Sha, Nanzando, Seiwa Shoten, Igaku-shoin and Technomics, all outside of the submitted work. Dr Yamada reports personal fees from Meiji Seika Pharma Co., Ltd., MSD K.K., Asahi Kasei Pharma Corporation, Seishin Shobo, Seiwa Shoten Co., Ltd., Igaku-shoin Ltd., Chugai Igakusha and Sentan Igakusha, all outside the submitted work. All other authors declare no competing interests. No funder had any role in the design and conduct of the study; collection, management, analysis and interpretation of the data; preparation, review or approval of the manuscript; and decision to submit the manuscript for publication.
The effect of tunnel cations on tunnel size in α-MnO2 structured (hollandite, cryptomelane) materials has long been of interest, as the tunnel size effects catalytic and transport properties. Previous research on the tunnel size has focused on potassium cryptomelane (KxMn8O16). This paper uses synthetic control of silver content in AgxMn8O16 to investigate the effect that tunnel silver occupancy has on the lattice parameters. Materials with silver (x) content between 1.14 and 1.66 were synthesized, synchrotron diffraction and Rietveld Refinement was used to determine lattice parameters. The lattice parameters were found to contract as silver content increases (from 9.774 Å to 9.738 Å), in contrast to previous investigations of other tunnel cations.
The present study is based on extensive sampling from an olistolith located near Castle Peak in the Taseko Lakes map area (British Columbia, Canada). The fauna is diverse and well preserved and similar to that illustrated from Monte Cetona in Italy by Fucini (1903).
The brain-derived neurotrophic factor (BDNF) Val66Met polymorphism Met allele exacerbates amyloid (Aβ) related decline in episodic memory (EM) and hippocampal volume (HV) over 36–54 months in preclinical Alzheimer's disease (AD). However, the extent to which Aβ+ and BDNF Val66Met is related to circulating markers of BDNF (e.g. serum) is unknown. We aimed to determine the effect of Aβ and the BDNF Val66Met polymorphism on levels of serum mBDNF, EM, and HV at baseline and over 18-months.
Non-demented older adults (n = 446) underwent Aβ neuroimaging and BDNF Val66Met genotyping. EM and HV were assessed at baseline and 18 months later. Fasted blood samples were obtained from each participant at baseline and at 18-month follow-up. Aβ PET neuroimaging was used to classify participants as Aβ– or Aβ+.
At baseline, Aβ+ adults showed worse EM impairment and lower serum mBDNF levels relative to Aβ- adults. BDNF Val66Met polymorphism did not affect serum mBDNF, EM, or HV at baseline. When considered over 18-months, compared to Aβ– Val homozygotes, Aβ+ Val homozygotes showed significant decline in EM and HV but not serum mBDNF. Similarly, compared to Aβ+ Val homozygotes, Aβ+ Met carriers showed significant decline in EM and HV over 18-months but showed no change in serum mBDNF.
While allelic variation in BDNF Val66Met may influence Aβ+ related neurodegeneration and memory loss over the short term, this is not related to serum mBDNF. Longer follow-up intervals may be required to further determine any relationships between serum mBDNF, EM, and HV in preclinical AD.
In cattle early gastrulation-stage embryos (Stage 5), four tissues can be discerned: (i) the top layer of the embryonic disc consisting of embryonic ectoderm (EmE); (ii) the bottom layer of the disc consisting of mesoderm, endoderm and visceral hypoblast (MEH); (iii) the trophoblast (TB); and (iv) the parietal hypoblast. We performed microsurgery followed by RNA-seq to analyse the transcriptome of these four tissues as well as a developmentally earlier pre-gastrulation embryonic disc. The cattle EmE transcriptome was similar at Stages 4 and 5, characterised by the OCT4/SOX2/NANOG pluripotency network. Expression of genes associated with primordial germ cells suggest their presence in the EmE tissue at these stages. Anterior visceral hypoblast genes were transcribed in the Stage 4 disc, but no longer by Stage 5. The Stage 5 MEH layer was equally similar to mouse embryonic and extraembryonic visceral endoderm. Our data suggest that the first mesoderm to invaginate in cattle embryos is fated to become extraembryonic. TGFβ, FGF, VEGF, PDGFA, IGF2, IHH and WNT signals and receptors were expressed, however the representative members of the FGF families differed from that seen in equivalent tissues of mouse embryos. The TB transcriptome was unique and differed significantly from that of mice. FGF signalling in the TB may be autocrine with both FGFR2 and FGF2 expressed. Our data revealed a range of potential inter-tissue interactions, highlighted significant differences in early development between mice and cattle and yielded insight into the developmental events occurring at the start of gastrulation.
Oregon's Fort Rock Cave is iconic in respect to both the archaeology of the northern Great Basin and the history of debate about when the Great Basin was colonized. In 1938, Luther Cressman recovered dozens of sagebrush bark sandals from beneath Mt. Mazama ash that were later radiocarbon dated to between 10,500 and 9350 cal B.P. In 1970, Stephen Bedwell reported finding lithic tools associated with a date of more than 15,000 cal B.P., a date dismissed as unreasonably old by most researchers. Now, with evidence of a nearly 15,000-year-old occupation at the nearby Paisley Five Mile Point Caves, we returned to Fort Rock Cave to evaluate the validity of Bedwell's claim, assess the stratigraphic integrity of remaining deposits, and determine the potential for future work at the site. Here, we report the results of additional fieldwork at Fort Rock Cave undertaken in 2015 and 2016, which supports the early Holocene occupation, but does not confirm a pre–10,500 cal B.P. human presence.
We present low-frequency spectral energy distributions of 60 known radio pulsars observed with the Murchison Widefield Array telescope. We searched the GaLactic and Extragalactic All-sky Murchison Widefield Array survey images for 200-MHz continuum radio emission at the position of all pulsars in the Australia Telescope National Facility (ATNF) pulsar catalogue. For the 60 confirmed detections, we have measured flux densities in 20 × 8 MHz bands between 72 and 231 MHz. We compare our results to existing measurements and show that the Murchison Widefield Array flux densities are in good agreement.
Glyphosate-resistant (GR) weeds have been a prime challenge to the sustainability of GR cotton-based production systems of the midsouthern United States. Barnyardgrass is known to be a high-risk species for evolving herbicide resistance, and a simulation model was developed for understanding the likelihood of glyphosate resistance evolution in this species in cotton-based systems. Under a worst-case scenario of five glyphosate applications in monoculture GR cotton, the model predicts resistance evolution in about 9 yr of continuous glyphosate use, with about 47% risk by year 15. A unique insight from this model is that management in response to GR Palmer amaranth in this system (a reactive response) provided a proactive means to greatly reduce the risks of glyphosate resistance evolution in barnyardgrass. Subsequent model analysis revealed that the risk of resistance is high in fields characterized by high barnyardgrass seedbank levels, seedling emergence, and seed production per square meter, whereas the risk is low in fields with high levels of postdispersal seed loss and annual seedbank loss. The initial frequency of resistance alleles was a high determinant of resistance evolution (e.g., 47% risk at year 15 at an initial frequency of 5e−8 vs. 4% risk at 5e−10). Monte Carlo simulations were performed to understand the influence of various glyphosate use patterns and production practices in reducing the rate and risk of glyphosate resistance evolution in barnyardgrass. Early planting and interrow cultivation are useful tools. Crop rotation is effective, but the diversity of weed management options practiced in the rotational crop is more important. Diversifying weed management options is the key, yet application timing and the choice of management option is critical. Model analyses illustrate the relative effectiveness of a number of diversified glyphosate use strategies in preventing resistance evolution and preserving the long-term utility of glyphosate in midsouthern U.S. cotton-based production systems.
Herbicide-resistant barnyardgrass has become widespread in the rice production systems of the midsouthern United States, leaving few effective herbicide options for controlling this weed. The acetolactate synthase (ALS)- and acetyl-CoA carboxylase (ACCase)-inhibiting herbicides remain largely effective in Clearfield® rice production, but strategies need to be developed to protect the long-term utility of these options. A two-trait model was developed to understand simultaneous evolution of resistance in barnyardgrass to the ALS- and ACCase-inhibiting herbicides in Clearfield rice. The model was used to predict resistance under a number of common weed management scenarios across 1,000 hypothetical rice fields in the Mississippi Delta region and answer some key management questions. Under an ALS inhibitor–only program consisting of three annual applications of imidazolinone herbicides (imazethapyr or imazamox) in continuous Clearfield rice, resistance was predicted within 4 yr with 80% risk by year 30. Weed management programs that consisted of ALS- and ACCase-inhibiting herbicides such as fenoxaprop and cyhalofop greatly reduced the risk of ALS-inhibiting herbicide resistance (12% risk by year 30), but there was a considerable risk for ACCase resistance (evolving by year 14 with 13% risk by year 30) and multiple resistance (evolving by year 16 with 11% risk by year 30) to both of these mechanisms of action. A unique insight was that failure to stop using a herbicide soon after resistance evolution can accelerate resistance to the subsequent herbicide option. Further, a strong emphasis on minimizing seedbank size is vital for any successful weed management strategy. Results also demonstrated that diversifying management options is not just adequate, but diversity combined with timely herbicide applications aimed at achieving high efficacy levels possible is imperative.
A simulation model is used to explore management options to mitigate risks of glyphosate resistance evolution in Palmer amaranth in glyphosate-resistant cotton in the southern United States. Our first analysis compares risks of glyphosate resistance evolution for seven weed-management strategies in continuous glyphosate-resistant cotton monoculture. In the “worst-case scenario” with five applications of glyphosate each year and no other herbicides applied, evolution of glyphosate resistance was predicted in 74% of simulated populations. In other strategies, glyphosate was applied with various combinations of preplant, PRE, and POST residual herbicides. The most effective strategy included four glyphosate applications with a preplant fomesafen application, and POST tank mixtures of glyphosate plus S-metolachlor followed by glyphosate plus flumioxazin. This strategy reduced the resistance risk to 12% of populations. A second series of simulations compared strategies where glyphosate-resistant cotton was grown in one-to-one rotations with corn or cotton with other herbicide resistance traits. In general, crop rotation reduced risks of resistance by approximately 50% and delayed the evolution of resistance by 2 to 3 yr. These analyses demonstrate that risks of glyphosate resistance evolution in Palmer amaranth can be reduced by reducing glyphosate use within and among years, controlling populations with diverse herbicide modes of action, and ensuring that population size is kept low. However, no strategy completely eliminated the risk of glyphosate resistance.
Previously undescribed plant and animal fossils from the Whidbey Formation represent two environments. An upper sand unit contains predominantly terrestrial molluscs (4 taxa), insects, and a vole (cf. Phenacomys), whereas a lower clay unit contains ostracodes (9 taxa), freshwater molluscs (6 taxa), insects (9 taxa), freshwater plant seeds (6 taxa), and fish (cf. Gasterosteus : stickleback). These taxa are compatible with interglacial climatic conditions on a coastal plain environment. The inferred freshwater and terrestrial environments of the Whidbey Formation imply local tectonic subsidence of the regional since the last interglaciation.