The Science of Open Spaces: Theory and Practice for Conserving Large, Complex Systems. Charles G. Curtin.

The phrase “open spaces,” may bring to mind expansive tracts of prairie, rangeland, or even desert, stretching lonely and unchanged to the horizon. Open spaces also could conjure open oceans or interstitial rural lands between urbanized hubs, dotted with farms, fields, and woodlands. In an abstract sense, open spaces could represent gaps in human understanding or blank spaces on a map. In his book The Science of Open Spaces, landscape ecologist Charles Curtin combines all these perspectives, expanding the definition of “open spaces” to multi-layered and multi-scaled complex systems that are “greater than the sum of their parts.” He populates these vastnesses with the diversity of species, hierarchy of biotic and abiotic interactions, and human social elements that comprise and link open spaces together as social-ecological systems. The Science of Open Spaces provides readers with a roadmap to 21st century land management, where the stakes are high, collaboration is crucial, and profound uncertainty in the face of the complexity often hampers decision-making

Activin Limits Progenitor Capability by Promoting Epithelial Cell Differentiation in the Mammary Gland

Transforming growth factor beta (TGF-beta) and activin utilize common signaling pathways, via smad2/3 and smad4, to mediate tumor suppression by effecting cell cycle arrest and apoptosis. Differences in temporal expression patterns suggest that each cytokine has specific roles in mammary gland development. Activin is expressed during pregnancy and lactation and is required for branching and lactogenesis, implying a role in mammary gland maturation. In contrast, TGF-beta is expressed during involution during mammary gland regression and functions to re-organize the mammary epithelial content to the non-lactating state. Previously, we found that TGF-beta and activin do share common signaling pathways allowing both cytokines to restrict the growth of mammary epithelial cells. However, extended exposure to TGF-beta (5ng/ml; 14 days) causes epithelial to mesencymal transition (EMT). The TGF-beta-treated cells were de-differentiated with loss of both luminal and basal markers. Activin treatment (50ng/ml; 14 days) did not activate EMT. Rather, activin promotes luminal epithelial differentiation with increased expression of prolactin receptor and luminal keratins. Therefore, to test the hypothesis that activin-treatment promotes luminal differentiation and decreases the proportion of progenitor cells in the epithelial population, we compared mammosphere forming capability in vitro and performed limiting dilution experiments in vivo by transplanting 50,000 or 500,000 pre-treated cells into cleared mouse mammary fat pads. The mammosphere assay showed that secondary mammospheres were significantly decreased in the activin-treated cells compared to both the control and TGF-beta treated cells. Tumor incidence between activin-treated and control cells were similar for transplants of 50,000 cells, but tumor incidence was significantly greater in TGF-beta-treated transplants. However, the activin-treated cells had poor outgrowth potential at both 50,000 and 500,000 cells relative to control. We conclude that activin may have the potential to reduce the stem cell population by promoting epithelial cell differentiation

The Algorithm Theoretical Basis Document for the Derivation of Range and Range Distributions from Laser Pulse Waveform Analysis for Surface Elevations, Roughness, Slope, and Vegetation Heights

The primary purpose of the GLAS instrument is to detect ice elevation changes over time which are used to derive changes in ice volume. Other objectives include measuring sea ice freeboard, ocean and land surface elevation, surface roughness, and canopy heights over land. This Algorithm Theoretical Basis Document (ATBD) describes the theory and implementation behind the algorithms used to produce the level 1B products for waveform parameters and global elevation and the level 2 products that are specific to ice sheet, sea ice, land, and ocean elevations respectively. These output products, are defined in detail along with the associated quality, and the constraints, and assumptions used to derive them

Disruption of CTCF-YY1-dependent looping of the human papillomavirus genome activates differentiation-induced viral oncogene transcription.

The complex life cycle of oncogenic human papillomavirus (HPV) initiates in undifferentiated basal epithelial keratinocytes where expression of the E6 and E7 oncogenes is restricted. Upon epithelial differentiation, E6/E7 transcription is increased through unknown mechanisms to drive cellular proliferation required to support virus replication. We report that the chromatin-organising CCCTC-binding factor (CTCF) promotes the formation of a chromatin loop in the HPV genome that epigenetically represses viral enhancer activity controlling E6/E7 expression. CTCF-dependent looping is dependent on the expression of the CTCF-associated Yin Yang 1 (YY1) transcription factor and polycomb repressor complex (PRC) recruitment, resulting in trimethylation of histone H3 at lysine 27. We show that viral oncogene up-regulation during cellular differentiation results from YY1 down-regulation, disruption of viral genome looping, and a loss of epigenetic repression of viral enhancer activity. Our data therefore reveal a key role for CTCF-YY1-dependent looping in the HPV life cycle and identify a regulatory mechanism that could be disrupted in HPV carcinogenesis

ANZAED eating disorder treatment principles and general clinical practice and training standards

Introduction: Eating disorders are complex to manage, and there is limited guidance around the depth and breadth of knowledge, skills and experience required by treatment providers. The Australia & New Zealand Academy for Eating Disorders (ANZAED) convened an expert group of eating disorder researchers and clinicians to define the clinical practice and training standards recommended for mental health professionals and dietitians providing treatment for individuals with an eating disorder. General principles and clinical practice standards were first developed, after which separate mental health professional and dietitian standards were drafted and collated by the appropriate members of the expert group. The subsequent review process included four stages of consultation and document revision: (1) expert reviewers; (2) a face-to-face consultation workshop attended by approximately 100 health professionals working within the sector; (3) an extensive open access online consultation process; and (4) consultation with key professional and consumer/carer stakeholder organisations. Recommendations: The resulting paper outlines and describes the following eight eating disorder treatment principles: (1) early intervention is essential; (2) co-ordination of services is fundamental to all service models; (3) services must be evidence-based; (4) involvement of significant others in service provision is highly desirable; (5) a personalised treatment approach is required for all patients; (6) education and/or psychoeducation is included in all interventions; (7) multidisciplinary care is required and (8) a skilled workforce is necessary. Seven general clinical practice standards are also discussed, including: (1) diagnosis and assessment; (2) the multidisciplinary care team; (3) a positive therapeutic alliance; (4) knowledge of evidence-based treatment; (5) knowledge of levels of care; (6) relapse prevention; and (7) professional responsibility. Conclusions: These principles and standards provide guidance to professional training programs and service providers on the development of knowledge required as a foundation on which to build competent practice in the eating disorder field. Implementing these standards aims to bring treatment closer to best practice, and consequently improve treatment outcomes, reduce financial cost to patients and services and improve patient quality of life

Evaluating more naturalistic outcome measures:A 1-year smartphone study in multiple sclerosis

Objective: In this cohort of individuals with and without multiple sclerosis (MS), we illustrate some of the novel approaches that smartphones provide to monitor patients with chronic neurologic disorders in their natural setting. Methods: Thirty-eight participant pairs (MS and cohabitant) aged 18–55 years participated in the study. Each participant received an Android HTC Sensation 4G smartphone containing a custom application suite of 19 tests capturing participant performance and patient-reported outcomes (PROs). Over 1 year, participants were prompted daily to complete one assigned test. Results: A total of 22 patients with MS and 17 cohabitants completed the entire study. Among patients with MS, low scores on PROs relating to mental and visual function were associated with dropout (p < 0.05). We illustrate several novel features of a smartphone platform. First, fluctuations in MS outcomes (e.g., fatigue) were assessed against an individual's ambient environment by linking responses to meteorological data. Second, both response accuracy and speed for the Ishihara color vision test were captured, highlighting the benefits of both active and passive data collection. Third, a new trait, a person-specific learning curve in neuropsychological testing, was identified using spline analysis. Finally, averaging repeated measures over the study yielded the most robust correlation matrix of the different outcome measures. Conclusions: We report the feasibility of, and barriers to, deploying a smartphone platform to gather useful passive and active performance data at high frequency in an unstructured manner in the field. A smartphone platform may therefore enable large-scale naturalistic studies of patients with MS or other neurologic diseases

Typical males and unconventional females: songs and singing behaviors of a tropical, duetting oriole in the breeding and non-breeding season

Sherpa Romeo green journal. Open access article. Creative Commons Attribution License (CC BY) applies.Recent research emphasizes that female song is evolutionarily important, yet there are still few species for which we have quantified the similarities and differences between male and female song. Comparing song rates and the structure of female and male song is an important first step to forming hypotheses about functional and evolutionary differences that may exist between females and males, especially in year-round territorial species that may use their songs for breeding and non-breeding activities. We compared female and male singing rates and song structure in a tropical New World oriole, the Venezuelan troupial (Icterus icterus) during both the breeding and non-breeding season and between the dawn and day. Males sang solos at particularly high rates during the breeding season before dawn. Females, however, sang at consistent rates year-round, primarily during the day. Females answered 75% of male day songs, producing duets, whereas males answered only 42% of female songs. Duets were common year-round, but occurred more often during the non-breeding season. Structurally, female songs were higher pitched and shorter than male songs. We detected no sex differences in the number or order of syllables, however, interestingly, answers were shorter than duet initiations and solos, and, during the breeding season, songs that initiated duets were characterized by higher syllable diversity than were answers or solos. The fact that males sing more during the breeding season supports the classical hypothesis that male song is a sexually selected trait. However, our findings that females sing solos and answer the majority of male songs to create duets year-round suggests that female song may have evolved to serve multiple functions not exclusively tied to breeding.Ye

Rapid nanopore sequencing and predictive susceptibility testing of positive blood cultures from intensive care patients with sepsis

ABSTRACT We aimed to evaluate the performance of Oxford Nanopore Technologies (ONT) sequencing from positive blood culture (BC) broths for bacterial identification and antimicrobial susceptibility prediction. Patients with suspected sepsis in four intensive care units were prospectively enrolled. Human-depleted DNA was extracted from positive BC broths and sequenced using ONT (MinION). Species abundance was estimated using Kraken2, and a cloud-based system (AREScloud) provided in silico predictive antimicrobial susceptibility testing (AST) from assembled contigs. Results were compared to conventional identification and phenotypic AST. Species-level agreement between conventional methods and AST predicted from sequencing was 94.2% (49/52), increasing to 100% in monomicrobial infections. In 262 high-quality AREScloud AST predictions across 24 samples, categorical agreement (CA) was 89.3%, with major error (ME) and very major error (VME) rates of 10.5% and 12.1%, respectively. Over 90% CA was achieved for some taxa (e.g.,Staphylococcus aureus) but was suboptimal for Pseudomonas aeruginosa. In 470 AST predictions across 42 samples, with both high quality and exploratory-only predictions, overall CA, ME, and VME rates were 87.7%, 8.3%, and 28.4%. VME rates were inflated by false susceptibility calls in a small number of species/antibiotic combinations with few representative resistant isolates. Time to reporting from sequencing could be achieved within 8–16 h from BC positivity. Direct sequencing from positive BC broths is feasible and can provide accurate predictive AST for some species. ONT-based approaches may be faster but significant improvements in accuracy are required before it can be considered for clinical use. IMPORTANCE Sepsis and bloodstream infections carry a high risk of morbidity and mortality. Rapid identification and susceptibility prediction of causative pathogens, using Nanopore sequencing direct from blood cultures, may offer clinical benefit. We assessed this approach in comparison to conventional phenotypic methods and determined the accuracy of species identification and susceptibility prediction from genomic data. While this workflow holds promise, and performed well for some common bacterial species, improvements in sequencing accuracy and more robust predictive algorithms across a diverse range of organisms are required before this can be considered for clinical use. However, results could be achieved in timeframes that are faster than conventional phenotypic methods