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Abstract Background Deletion or duplication in the DMD gene is one of the most common causes of Duchenne and Becker muscular dystrophy (DMD/BMD). However, the pathogenicity of complex rearrangements involving DMD, especially segmental duplications with unknown breakpoints, is not well understood. This study aimed to evaluate the structure, pattern, and potential impact of rearrangements involving DMD duplication. Methods Two families with DMD segmental duplications exhibiting phenotypical differences were recruited. Optical genome mapping (OGM) was used to explore the cryptic pattern of the rearrangements. Breakpoints were validated using long-range polymerase chain reaction combined with next-generation sequencing and Sanger sequencing. Results A multi-copy duplication involving exons 64–79 of DMD was identified in Family A without obvious clinical symptoms. Family B exhibited typical DMD neuromuscular manifestations and presented a duplication involving exons 10–13 of DMD. The rearrangement in Family A involved complex in-cis tandem repeats shown by OGM but retained a complete copy (reading frame) of DMD inferred from breakpoint validation. A reversed insertion with a segmental repeat was identified in Family B by OGM, which was predicted to disrupt the normal structure and reading frame of DMD after confirming the breakpoints. Conclusions Validating breakpoint and rearrangement pattern is crucial for the functional annotation and pathogenic classification of genomic structural variations. OGM provides valuable insights into etiological analysis of DMD/BMD and enhances our understanding for cryptic effects of complex rearrangements.

Background: Deletion or duplication in the DMD gene is one of the most common causes of Duchenne and Becker muscular dystrophy (DMD/BMD). However, the pathogenicity of complex rearrangements involving DMD, especially segmental duplications with unknown breakpoints, is not well understood. This study aimed to evaluate the structure, pattern, and potential impact of rearrangements involving DMD duplication. Methods: Two families with DMD segmental duplications exhibiting phenotypical differences were recruited. Optical genome mapping (OGM) was used to explore the cryptic pattern of the rearrangements. Breakpoints were validated using long-range polymerase chain reaction combined with next-generation sequencing and Sanger sequencing. Results: A multi-copy duplication involving exons 64–79 of DMD was identified in Family A without obvious clinical symptoms. Family B exhibited typical DMD neuromuscular manifestations and presented a duplication involving exons 10–13 of DMD. The rearrangement in Family A involved complex in-cis tandem repeats shown by OGM but retained a complete copy (reading frame) of DMD inferred from breakpoint validation. A reversed insertion with a segmental repeat was identified in Family B by OGM, which was predicted to disrupt the normal structure and reading frame of DMD after confirming the breakpoints. Conclusions: Validating breakpoint and rearrangement pattern is crucial for the functional annotation and pathogenic classification of genomic structural variations. OGM provides valuable insights into etiological analysis of DMD/BMD and enhances our understanding for cryptic effects of complex rearrangements. [ABSTRACT FROM AUTHOR]

ABSTRACT Dermabacter hominis, a short gram-positive rod, is a part of the human skin flora, but can also cause infections (e.g., skin and soft tissue infections, bone and joint infections, abscesses, peritoneal dialysis-associated peritonitis, and bacteremia). Only limited data are available for antimicrobial resistance rates. Although CLSI does include coryneform genera in Corynebacterium spp. clinical breakpoints, they point out that only limited data are available on resistance rates. The aim of this study was to assess the minimal inhibitory concentration (MIC) of clinical isolates of D. hominis and to deduce breakpoints for disk diffusion. D. hominis (n = 30) from five laboratories in Germany were tested by broth microdilution and disk diffusion method. MICs were interpreted according to current clinical breakpoints for Corynebacterium spp. or pharmacokinetic–pharmacodynamic breakpoints (EUCAST). To deduce breakpoints for disk diffusion, MICs were correlated with inhibition zone diameters. All isolates were susceptible to vancomycin, rifampicin, and linezolid (100%, n = 30/30). Lower susceptibility rates were found for ampicillin (83%, n = 25/30) followed by ceftriaxone (37%, n = 11/30) and clindamycin (27%, n = 8/30). All isolates were resistant to benzylpenicillin and daptomycin. Good correlations between disk diffusion and MIC (suggested breakpoints for susceptibility in brackets) were found for ampicillin (S ≥ 10 mm), ceftriaxone (S ≥ 24 mm), clindamycin (S ≥ 19 mm), levofloxacin (I ≥ 24 mm), linezolid (S ≥ 29 mm), rifampicin (S ≥ 38 mm), and vancomycin (S ≥ 21 mm). Due to limited variances in both MIC values and inhibition zone diameters, no disk diffusion breakpoint could be deduced for gentamicin and benzylpenicillin in our dataset. D. hominis has favorable susceptibility rates for vancomycin, rifampicin, and linezolid and shows correlations between MIC and disk diffusion diameter for selected antimicrobial agents. Thus, the development of clinical breakpoints for disk diffusion appears feasible.IMPORTANCEDermabacter hominis can cause infections in humans (e.g., skin and soft tissue infections, bone and joint infections, abscesses, peritoneal dialysis-associated peritonitis, and bacteremia). Currently, only limited data are available regarding the resistance rates of this specific pathogen. Data for the easy accessible disk diffusion method are missing. We were able to provide additional data on resistance rates of clinical D. hominis isolates to common antimicrobial agents and correlate these with disk diffusion diameters to derive breakpoints to further improve the antimicrobial susceptibility testing for this specific pathogen. In addition to that, we created a current overview of resistance rates from the existing literature. Our data provide deeper insight into resistance rates and antimicrobial susceptibility testing of this specific pathogen.

Introduction: The escalating prevalence of multidrug resistance is a global threat to human health particularly in critically ill patients with bloodstream infections (BSIs). Delay in the administration of the appropriate antimicrobial treatment is associated with higher mortality rates and adverse consequences. This study attempted to estimate the rapid antimicrobial susceptibility testing (RAST) breakpoints directly from flagged BacT/Alert blood culture bottles in clinical practice. Material & Methods: A descriptive, cross-sectional study conducted at a tertiary care hospital in Delhi over a period of two months. The RAST was performed directly from the clinical samples for blood cultures received in our laboratory in parallel with the routine antimicrobial testing as per standard CLSI guidelines. Blood cultures were routinely incubated in BacT/Alert 3D. The inhibition zones were read at 4, 6, 8 and 16-20 hour of incubation as per European Committee on Antimicrobial Susceptibility Testing (EUCAST) guidelines. The identification of the isolates was confirmed by Vitek-2 compact system. Results: In our study, the area of technical uncertainty (ATU) percentage was initially high at 4 hours but decreased significantly in later incubation periods. At 4 hours, none of the S. aureus isolates showed >90% categorical agreement (CA) for any antimicrobial tested. However, clindamycin achieved the highest CA (100%) at 6 hours and 90% thereafter, with no very major errors (VME) or major error (ME). Cefoxitin required 8 hours to reach >90% CA, with no VME observed at any time point, but up to 75% ME at 8 hours. At 4 hours, most antimicrobials had high (>1.5%) rates of VME among Enterobacteriales. By 6 hours, only Meropenem and Gentamicin had >90% CA, with no VME observed for other antibiotics. Conclusion: The RAST method is relatively easy to implement in clinical microbiology labs, offering cost-effectiveness, simplicity, and rapid results, especially in resource-limited settings. However, reporting RAST results can be complex due to potential challenges with CA, VME, and ME, particularly in the initial hours of incubation and within the ATU. [ABSTRACT FROM AUTHOR]

Introduction: The escalating prevalence of multidrug resistance is a global threat to human health particularly in critically ill patients with bloodstream infections (BSIs). Delay in the administration of the appropriate antimicrobial treatment is associated with higher mortality rates and adverse consequences. This study attempted to estimate the rapid antimicrobial susceptibility testing (RAST) breakpoints directly from flagged BacT/Alert blood culture bottles in clinical practice. Material & Methods: A descriptive, cross-sectional study conducted at a tertiary care hospital in Delhi over a period of two months. The RAST was performed directly from the clinical samples for blood cultures received in our laboratory in parallel with the routine antimicrobial testing as per standard CLSI guidelines. Blood cultures were routinely incubated in BacT/Alert 3D. The inhibition zones were read at 4, 6, 8 and 16-20 hour of incubation as per European Committee on Antimicrobial Susceptibility Testing (EUCAST) guidelines. The identification of the isolates was confirmed by Vitek-2 compact system. Results: In our study, the area of technical uncertainty (ATU) percentage was initially high at 4 hours but decreased significantly in later incubation periods. At 4 hours, none of the S. aureus isolates showed >90% categorical agreement (CA) for any antimicrobial tested. However, clindamycin achieved the highest CA (100%) at 6 hours and 90% thereafter, with no very major errors (VME) or major error (ME). Cefoxitin required 8 hours to reach >90% CA, with no VME observed at any time point, but up to 75% ME at 8 hours. At 4 hours, most antimicrobials had high (>1.5%) rates of VME among Enterobacteriales. By 6 hours, only Meropenem and Gentamicin had >90% CA, with no VME observed for other antibiotics. Conclusion: The RAST method is relatively easy to implement in clinical microbiology labs, offering cost-effectiveness, simplicity, and rapid results, especially in resource-limited settings. However, reporting RAST results can be complex due to potential challenges with CA, VME, and ME, particularly in the initial hours of incubation and within the ATU.

Abstract Background Large deletions and duplications within the low-density lipoprotein receptor (LDLR) gene make up approximately 10% of LDLR pathogenic variants found in Czech patients with familial hypercholesterolemia. The goal of this study was to test the hypothesis that all probands with each rearrangement share identical breakpoints inherited from a common ancestor and to determine the role of Alu repetitive elements in the generation of these rearrangements. Methods The breakpoint sequence was determined by PCR amplification and Sanger sequencing. To confirm the breakpoint position, an NGS analysis was performed. Haplotype analysis of common LDLR variants was performed using PCR and Sanger sequencing. Results The breakpoints of 8 rearrangements within the LDLR gene were analysed, including the four most common LDLR rearrangements in the Czech population (number of probands ranging from 8 to 28), and four less common rearrangements (1–4 probands). Probands with a specific rearrangement shared identical breakpoint positions and haplotypes associated with the rearrangement, suggesting a shared origin from a common ancestor. All breakpoints except for one were located inside an Alu element. In 6 out of 8 breakpoints, there was high homology (≥ 70%) between the two Alu repeats in which the break occurred. Conclusions The most common rearrangements of the LDLR gene in the Czech population likely arose from one mutational event. Alu elements likely played a role in the generation of the majority of rearrangements inside the LDLR gene.

Background: Using the pencil beam raster scanning method employed at most carbon beam treatment facilities, spots can be moved without interrupting the beam, allowing for the delivery of a dose between spots (move dose). This technique is also known as Dose‐Driven‐Continuous‐Scanning (DDCS). To minimize its impact on HIMAK patient dosimetry, there's an upper limit to the move dose. Spots within a layer are grouped into sets, or "break points," allowing continuous irradiation. The beam is turned off when transitioning between sets or at the end of a treatment layer or spill. The control system beam‐off is accomplished by turning off the RF Knockout (RFKO) extraction and after a brief delay the High Speed Steering Magnet (HSST) redirects the beam transport away from isocenter to a beam dump. Purpose: The influence of the move dose and beam on/off control on the dose distribution and irradiation time was evaluated by measurements never before reported and modelled for Hitachi Carbon DDCS. Method: We conducted fixed‐point and scanning irradiation experiments at three different energies, both with and without breakpoints. For fixed‐point irradiation, we utilized a 2D array detector and an oscilloscope to measure beam intensity over time. The oscilloscope data enabled us to confirm beam‐off and beam‐on timing due to breakpoints, as well as the relative timing of the RFKO signal, HSST signal, and dose monitor (DM) signals. From these measurements, we analyzed and modelled the temporal characteristics of the beam intensity. We also developed a model for the spot shape and amplitude at isocenter occurring after the beam‐off signal which we called flap dose and its dependence on beam intensity. In the case of scanning irradiation, we measured move doses using the 2D array detector and compared these measurements with our model. Result: We observed that the most dominant time variation of the beam intensity was at 1 kHz and its harmonic frequencies. Our findings revealed that the derived beam intensity cannot reach the preset beam intensity when each spot belongs to different breakpoints. The beam‐off time due to breakpoints was approximately 100 ms, while the beam rise time and fall time (tdecay) were remarkably fast, about 10 ms and 0.2 ms, respectively. Moreover, we measured the time lag (tdelay) of approximately 0.2 ms between the RFKO and HSST signals. Since tdelay ≈ tdecay at HIMAK then the HSST is activated after the residual beam intensity, resulting in essentially zero flap dose at isocenter from the HSST. Our measurements of the move dose demonstrated excellent agreement with the modelled move dose. Conclusion: We conducted the first move dose measurement for a Hitachi Carbon synchrotron, and our findings, considering beam on/off control details, indicate that Hitachi's carbon synchrotron provides a stable beam at HIMAK. Our work suggests that measuring both move dose and flap dose should be part of the commissioning process and possibly using our model in the Treatment Planning System (TPS) for new facilities with treatment delivery control systems with higher beam intensities and faster beam‐off control. [ABSTRACT FROM AUTHOR]

Background: Large deletions and duplications within the low-density lipoprotein receptor (LDLR) gene make up approximately 10% of LDLR pathogenic variants found in Czech patients with familial hypercholesterolemia. The goal of this study was to test the hypothesis that all probands with each rearrangement share identical breakpoints inherited from a common ancestor and to determine the role of Alu repetitive elements in the generation of these rearrangements. Methods: The breakpoint sequence was determined by PCR amplification and Sanger sequencing. To confirm the breakpoint position, an NGS analysis was performed. Haplotype analysis of common LDLR variants was performed using PCR and Sanger sequencing. Results: The breakpoints of 8 rearrangements within the LDLR gene were analysed, including the four most common LDLR rearrangements in the Czech population (number of probands ranging from 8 to 28), and four less common rearrangements (1–4 probands). Probands with a specific rearrangement shared identical breakpoint positions and haplotypes associated with the rearrangement, suggesting a shared origin from a common ancestor. All breakpoints except for one were located inside an Alu element. In 6 out of 8 breakpoints, there was high homology (≥ 70%) between the two Alu repeats in which the break occurred. Conclusions: The most common rearrangements of the LDLR gene in the Czech population likely arose from one mutational event. Alu elements likely played a role in the generation of the majority of rearrangements inside the LDLR gene. [ABSTRACT FROM AUTHOR]

Purpose of Review: This review outlines the process of setting and revising Clinical and Laboratory Standards Institute (CLSI) breakpoints and summarizes breakpoints approved in 2023. These breakpoints will be published in the 2024 edition of the CLSI M100 document. Recent Findings: Over the past decade, new rapid diagnostic tests and antibiotic approvals have led to more frequent updates and revisions to clinical breakpoints—or susceptibility test interpretive criteria (STIC). CLSI is currently the only recognized standards development organization—outside of the FDA—allowed to set or revise STIC. The process of setting breakpoints is not always clear-cut because data evaluation can be limited by a lack of published data in one of three required categories (microbiologic, pharmacokinetic/pharmacodynamics, and clinical outcomes) detailed in the CLSI M23 document. Summary: Antimicrobial susceptibility testing is a foundation for optimal antimicrobial therapy and plays a critical role in monitoring the spread of antimicrobial resistance. [ABSTRACT FROM AUTHOR]

Abstract Background Biallelic loss-of-function variants in WWOX cause WWOX-related epileptic encephalopathy (WOREE syndrome), which has been reported in 60 affected individuals to date. In this study, we report on an affected individual with WOREE syndrome who presented with early-onset refractory seizures and global neurodevelopmental delay and died at the age of two and a half years. Methods We present clinical and molecular findings in the affected individual, including biallelic pathogenic variants in the WWOX gene. We employed different molecular approaches, such as whole exome sequencing, quantitative real-time polymerase chain reaction (qPCR), and whole-genome sequencing, to identify the genetic variants. The breakpoints were determined through gap PCR and Sanger sequencing. Result Whole exome sequencing revealed homozygous exon 6 deletion in the WWOX gene in the proband. Quantitative real-time PCR confirmed that the parents were heterozygous carriers of exon 6 deletion. However, using whole-genome sequencing, we identified three larger deletions (maternal allele with exon 6–8 deletion and paternal allele with two deletions in proximity one in intron 5 and the other in exon 6) involving the WWOX gene in the proband, with deletion sizes of 13,261 bp, 53,904 bp, and 177,200 bp. The exact breakpoints were confirmed through gap PCR and Sanger sequencing. We found that the proband inherited the discontinuous deletion of intron 5 and exon 6 from the father, and the exons 6–8 deletion from the mother using gap PCR. Conclusion Our findings extend the variant spectrum of WOREE syndrome and support the critical role of the WWOX gene in neural development.

Violence in partner relationships is a very serious social problem, which in the Czech Republic is dominantly burdened for women. In cases of partner relationships where violence is present, it may take a relatively long time before the victim of violence can detach from the partner and end the violent relationship. In this process, the victim of violence has to overcome many obstacles, and even after leaving an abusive partner, there is no guarantee that the violence will end. The presented research study focuses on the comprehensive mapping of violent partner relationships. On the origin and development of violence, termination of violent relationships and subsequent communication between ex-partners. Analyzes of qualitative case studies are presented, which were conducted on a sample of seven women who experienced some form of violence in their partner relationships, and at the same time managed to end the violent relationship. The data was collected using semi-structured interviews, and lifelines from November 2020 to February 2021. The text points to individual turning points that lead to the termination of partnership relationships. It captures the widespread occurrence of ongoing partner violence after leaving a violent partner, which, however, is not reflected much in the legislation of the Czech Republic. Barriers to leaving violent relationships and the effects of violence on the lives of persons threatened by this phenomenon are also described in more detail. [ABSTRACT FROM AUTHOR]

In this article, three approaches for detecting outliers, breakpoints and/or level shifts in time series are discussed. These approaches are then applied in a short financial time series with the generic aim to estimate the possible opportunity loss due to the occurrence of these points. [ABSTRACT FROM AUTHOR]

The rapid emergence of multi-drug resistant Gram-negative pathogens has driven the introduction of novel β-lactam combination agents (BLCs) to the antibiotic market: ceftolozane-tazobactam, ceftazidime-avibactam, meropenem-vaborbactam, imipenem-relebactam, cefiderocol, and sulbactam-durlobactam. These agents are equipped with innovative mechanisms that confer broad Gram-negative activity, notably against certain challenging carbapenemases. While their introduction offers a beacon of hope, clinical microbiology laboratories must navigate the complexities of susceptibility testing for these agents due to their diverse activity profiles against specific β-lactamases and the possibility of acquired resistance mechanisms in some bacterial isolates. This review explores the complexities of these novel antimicrobial agents detailing the intricacies of their application, providing guidance on the nuances of susceptibility testing, interpretation, and result reporting in clinical microbiology laboratories. [ABSTRACT FROM AUTHOR]

We comprehensively investigate the robustness of well-known factor models to altered factor formation breakpoints. Deviating from the standard 30th and 70th percentile selection, we use an extensive set of anomaly test portfolios to uncover two main findings: First, there is a trade-off between specification and diversification. More centered breakpoints tend to result in less (idiosyncratic) risk. More extreme sorts lead to greater exposure to the underlying anomalies and thus to higher average returns. Second, the models are robust to varying degrees. Hou et al.'s model [2015, Digesting Anomalies: An Investment Approach, Review of Financial Studies 28, 650–705] is much more sensitive to changes in breakpoints than the Fama–French models. [ABSTRACT FROM AUTHOR]

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Background: Biallelic loss-of-function variants in WWOX cause WWOX-related epileptic encephalopathy (WOREE syndrome), which has been reported in 60 affected individuals to date. In this study, we report on an affected individual with WOREE syndrome who presented with early-onset refractory seizures and global neurodevelopmental delay and died at the age of two and a half years. Methods: We present clinical and molecular findings in the affected individual, including biallelic pathogenic variants in the WWOX gene. We employed different molecular approaches, such as whole exome sequencing, quantitative real-time polymerase chain reaction (qPCR), and whole-genome sequencing, to identify the genetic variants. The breakpoints were determined through gap PCR and Sanger sequencing. Result: Whole exome sequencing revealed homozygous exon 6 deletion in the WWOX gene in the proband. Quantitative real-time PCR confirmed that the parents were heterozygous carriers of exon 6 deletion. However, using whole-genome sequencing, we identified three larger deletions (maternal allele with exon 6–8 deletion and paternal allele with two deletions in proximity one in intron 5 and the other in exon 6) involving the WWOX gene in the proband, with deletion sizes of 13,261 bp, 53,904 bp, and 177,200 bp. The exact breakpoints were confirmed through gap PCR and Sanger sequencing. We found that the proband inherited the discontinuous deletion of intron 5 and exon 6 from the father, and the exons 6–8 deletion from the mother using gap PCR. Conclusion: Our findings extend the variant spectrum of WOREE syndrome and support the critical role of the WWOX gene in neural development. [ABSTRACT FROM AUTHOR]

IntroductionRecombination serves as a common strategy employed by RNA viruses for their genetic evolution. Extensive genomic surveillance during the COVID-19 pandemic has reported SARS-CoV-2 Recombinant strains indicating recombination events during the viral evolution. This study introspects the phenomenon of genome recombination by tracing the footprint of prominent lineages of SARS-CoV-2 at different time points in the context of on-going evolution and emergence of Recombinants.MethodWhole genome sequencing was carried out for 2,516 SARS-CoV-2 (discovery cohort) and 1,126 (validation cohort) using nasopharyngeal samples collected between the time period of March 2020 to August 2022, as part of the genomic surveillance program. The sequences were classified according to the different lineages of SARS-CoV-2 prevailing in India at respective time points.ResultsMutational diversity and abundance evaluation across the 12 lineages identified 58 Recombinant sequences as harboring the least number of mutations (n = 111), with 14 low-frequency unique mutations with major chunk of mutations coming from the BA.2. The spontaneously/dynamically increasing and decreasing trends of mutations highlight the loss of mutations in the Recombinants that were associated with the SARS-CoV-2 replication efficiency, infectivity, and disease severity, rendering them functionally with low infectivity and pathogenicity. Linkage disequilibrium (LD) analysis revealed that mutations comprising the LD blocks of BA.1, BA.2, and Recombinants were found as minor alleles or as low-frequency alleles in the LD blocks from the previous SARS-CoV-2 variant samples, especially Pre-VOC. Moreover, a dissipation in the size of LD blocks as well as LD decay along with a high negative regression coefficient (R squared) value was demonstrated in the Omicron and BA.1 and BA.2 lineages, which corroborated with the breakpoint analysis.ConclusionTogether, the findings help to understand the evolution and emergence of Recombinants after the Omicron lineages, for sustenance and adaptability, to maintain the epidemic spread of SARS-CoV-2 in the host population already high in immunity levels.

Precipitation is a highly variable meteorological element. Similarly, to other meteorological elements (e.g. temperature), the changes in the measurement practices or in the environment can cause inhomogeneities in the precipitation data series. Therefore, homogenization of precipitation data series is necessary before studying the long‐term climate change. In this paper we present the main features of the MASH procedure, which we use to produce homogenized climate datasets for Hungary at the Climate Department of the Hungarian Meteorological Service (OMSZ). Due to the increasing number of discontinued precipitation stations, the number of missing data has increased significantly; therefore the station networks used for precipitation homogenization have been completely renewed. With this renewal, the percentage of missing data has been minimized, the number of data series has been increased and a denser station network is now used in mountainous areas where the spatial variability of precipitation is the highest. As a result, a new, more homogeneous, representative precipitation database of Hungary from 1901 to the present has been created. In the paper, we also examine the main characteristics of the detected inhomogeneities, with examples of the main types of inhomogeneities for some stations. [ABSTRACT FROM AUTHOR]

Abstract Background Balanced reciprocal translocation (BRT) is one of the most common chromosomal abnormalities that causes infertility, recurrent miscarriage, and birth defects. Preimplantation genetic testing (PGT) is widely used to select euploid embryos for BRT carriers to increase the chance of a healthy live birth. Several strategies can be used to distinguish reciprocal translocation carrier embryos from those with a normal karyotype; however, these techniques are time-consuming and difficult to implement in clinical laboratories. In this study, nanopore sequencing was performed in two reciprocal translocation carriers, and the results were validated using the next-generation sequencing-based method named, “Mapping Allele with Resolved Carrier Status” (MaReCs). Results The translocation breakpoints in both reciprocal translocation carriers were accurately identified by nanopore sequencing and were in accordance with the results obtained using MaReCs. More than one euploid non-balanced translocation carrier embryo was identified in both patients. Amniocentesis results revealed normal karyotypes, consistent with the findings by MaReCs and nanopore sequencing. Conclusion Our results suggest that nanopore sequencing is a powerful strategy for accurately distinguishing non-translocation embryos from translocation carrier embryos and precisely localizing translocation breakpoints, which is essential for PGT and aids in reducing the propagation of reciprocal translocation in the population.

Abstract Background Fetal skeletal dysplasia (SD) is a common congenital disability comprising a complex group of skeletal disorders with substantial clinical and genetic heterogeneity. Many of these defects are detected prenatally using ultrasound (US). However, the diagnostic accuracy of the US is limited. Methods We recruited 55 unrelated fetuses with US-detected skeletal anomalies and performed sequential tests using copy number variation sequencing, targeted skeletal gene panel sequencing, or whole exome sequencing. The detected variants were validated using Sanger sequencing or multiplex ligation-dependent probe amplification. We conducted breakpoint analysis and structural modeling of variants possibly involved in fetal SD. Results A definitive diagnosis was achieved in 81.82% of affected fetuses (45/55). We identified chromosomal abnormalities in seven cases and 36 variants, of which 18 were novel pathogenic or likely pathogenic in 11 genes in 38 cases. De novo variants were identified in 27 cases (71.05%, 27/38), and one gonosomal mosaicism variant was found in the mother of one fetus. Our case examples demonstrated the high heterogeneity of fetal SDs and the rare fetal SD-associated challenges. Conclusions Careful clinical evaluation of fetuses with SD can guide appropriate molecular testing. Our study extends the SD-associated pathogenic variant spectrum and provides useful genetic counselling guidance and an accurate prenatal diagnosis strategy.

A good understanding of the processes of land surface temperature (LST) change is important for assessing regional climate change. In the present study, we obtained the MODIS MOD11A2 LST products over the Yangtze River Delta (YRD) from 2001 to 2020. In order to comprehensively assess the spatial and temporal variability of LST in the YRD region over the past two decades, the Theil–Sen Median trend analysis and Mann–Kendall test, BFAST01 trend decomposition, and landscape pattern analysis were used in this study. We show that the rate of linear change in LST in the YRD ranges from −0.019 °C/month to 0.046 °C/month. The BFAST01 trend decomposition identifies more details of LST change and monotonic increases, reversal increase, and interruption increase are the main warming trends. The distribution of the different trend types shows strong aggregation with high spatial heterogeneity. The LST breakpoints are mainly located in the northern and southern YRD, which frequently occurred during 2010–2013. Of the various land types, breakpoints occur most frequently in cropland and high NDVI (0.5–0.7) areas, and the intensity of most of them is within 2 °C. In addition, much stronger warming occurs in urban areas than in other land types. Our study provides a better understanding of the dynamics of LST in the YRD region over the past 20 years and highlights that breakpoints cannot be circumvented in regional temperature assessment. [ABSTRACT FROM AUTHOR]

Pedogenic thresholds describe where soil properties or processes change in an abrupt/nonlinear fashion in response to small changes in environmental forcing. Contrastingly, soil process domains refer to the space between thresholds where soil properties are either unchanged, or change gradually, across a broad range of environmental forcing. Here, we test quantitatively for the presence of thresholds in patterns of soil properties across a climatic gradient on soils developed from ~20 ky old basaltic substrate on the Island of Hawai'i. From multiple soil properties, we quantitatively identified a threshold at ~750 mm/y of water balance (precipitation minus potential evapotranspiration), delineating the upper water balance boundary of soil fertility in these soils. From the threshold in the ratio of exchangeable Ca to total Ca we identified the lower water balance boundary of soil fertility in these soils at -1000 mm/y, however this threshold was qualitatively described as it lies near the limit of the climate gradient data where the statistical approach can not be applied. These two results represent the first time that pedogenic thresholds have been identified using statistically rigorous methods and the limitations of said methods, respectively. Comparing the 20 ky soils to soils that developed on basaltic substrates of 1.2 ky, 7.5 ky, 150 ky, and 4100 ky in a time-climate matrix, we found that our quantitative analysis supports previous qualitatively identified thresholds in the soils developed from older substrates. We also identified the 20 ky as the transition from kinetic to supply limitation for plant nutrients in soil in this system.

Terrestrial gross primary productivity (GPP) is an important flux that drives the global carbon cycle. However, quantifying the trend and the control factor of GPP from the pixel level to the regional level is still a challenge. We generated monthly GPP dataset using the vegetation photosynthesis model and calculated the interannual linear trend for China during 2000-2016. The Breaks For Additive Seasonal and Trend method was applied to detect the timing of breakpoint and trends shift of monthly GPP, while boosted regression tree analysis was used to identify the most important factor and its relative influence on GPP based on gridded leaf area index (LAI), aerosol optical thickness, and NCEP-DOE Reanalysis II meteorological data. The results show that annual mean GPP was significantly (P < 0.001, R 2 = 0.78) increased, especially in the Loess Plateau and South China, from 2000 to 2016. The change rate of annual mean GPP declined from 18.82 g C m-2 yr-1 in 2000-2008 to 3.48 g C m-2 yr-1 in 2008-2016. About 55.4% of the breakpoints occur between 2009 and 2011 and was mainly distributed in Qinghai-Tibet Plateau, Central China, Southwestern China, and South China, and negative oriented GPP trends variation type still accounts for about 28.76%. LAI and temperature related factors generally had the highest relative influence on GPP in the north part and south part of China, respectively. Our study indicates that the ecological restoration projects and rapid urbanization have respectively induced the most obvious increase and decrease trends of GPP in China. Land cover change and climate change are the main reasons for GPP dynamics in the north and south part of China, respectively.

Microbiological testing, including interpretation of antimicrobial susceptibility testing results using current breakpoints, is crucial for clinical care and infection control. Continued use of obsolete Enterobacteriaceae carbapenem breakpoints is common in clinical laboratories. The purposes of this study were (i) to determine why laboratories failed to update breakpoints and (ii) to provide support for breakpoint updates. The Los Angeles County Department of Public Health conducted a 1-year outreach program for 41 hospitals in Los Angeles County that had reported, in a prior survey of California laboratories, using obsolete Enterobacteriaceae carbapenem breakpoints. In-person interviews with hospital stakeholders and customized expert guidance and resources were provided to aid laboratories in updating breakpoints, including support from technical representatives from antimicrobial susceptibility testing device manufacturers. Forty-one hospitals were targeted, 7 of which had updated breakpoints since the prior survey. Of the 34 remaining hospitals, 27 (79%) assumed that their instruments applied current breakpoints, 17 (50%) were uncertain how to change breakpoints, and 10 (29%) lacked resources to perform a validation study for off-label use of the breakpoints on their systems. Only 7 hospitals (21%) were familiar with the FDA/CDC Antibiotic Resistance Isolate Bank. All hospitals launched a breakpoint update process; 16 (47%) successfully updated breakpoints, 12 (35%) received isolates from the CDC in order to validate breakpoints on their systems, and 6 (18%) were planning to update within 1 year. The public health intervention was moderately successful in identifying and overcoming barriers to updating Enterobacteriaceae carbapenem breakpoints in Los Angeles hospitals. However, the majority of targeted hospitals continued to use obsolete breakpoints despite 1 year of effort. These findings have important implications for the quality of patient care and patient safety. Other public health jurisdictions may want to utilize similar resources to bridge the patient safety gap, while manufacturers, the FDA, and others determine how best to address this growing public health issue.

The Mediterranean region is considered to be highly affected by climate change with rainfall deficits leading to a significant decrease in river discharge. This study aims to assess the impacts of climate change on water resources in a Mediterranean catchment, namely the Bas-Loukkos catchment (Morocco), where pressure on the water resources is already present due to intensive hydro-agricultural development and is likely to increase. Mann–Kendall, Pettitt and Buishand tests were used to analyze trends and detect breakpoints in discharge and precipitation time series over the period 1960–2018. The precipitation–specific discharge relationships has been analysed by the double-mass curve (DMC). The analyses highlighted a decreasing trend in precipitation. A significant breakpoint was detected in early 1970s, with mean annual precipitation decreasing by 16–26% after this period. Discharge decreased by approximately 35% beginning in the late 1970s/early 1980s. The DMC showed different patterns between ‘undisturbed’ sub-catchments and two intensively managed sub-catchments. Wettest Mediterranean catchments are often considered as future water reservoirs to support part of the water needs in arid catchments. This study highlights that such catchments may already be impacted by climate changes, with discharge decreasing, and by water human activities that exert a major pressure on water resources. HIGHLIGHTS Evaluation of trends and detection of breaks in precipitation and discharge based on non-parametric statistical tests.; Analyses of the precipitation–discharge relationship in different sub-catchments.; Evaluation of the impact of climate change and human activities on catchment hydrology.;

Global institutional changes (GICs), having influenced energy prices, led to a steady upward trend in carbon prices on the EU ETS. The aim of the article is to assess the changes in the relationship between carbon prices and energy prices under GICs. The Bai–Perron tests for structural breaks identified two dates as the breakpoint, 21 April 2016 and 21 September 2020. We test the hypothesis that powerful external factors (GIC) are changing the trend pattern of the carbon price time series. New pricing rules of the carbon price are being formed after the breakpoint. We use daily observations from 4 January 2010 to 1 September 2022. We use GARCH models with multiple stationary time series to discover a relationship energy price with the carbon price before and after the break points. We found that three models for two breakpoints better describe the relationship between carbon prices and energy prices than two models for one breakpoint, much less one model for the entire period. We find that the carbon price depends on energy prices, especially on the price of oil, in a statistically significant way, but the gas price is not statistically significant after 21 September 2020. [ABSTRACT FROM AUTHOR]

The rapid emergence of multi-drug resistant Gram-negative pathogens has driven the introduction of novel β-lactam combination agents (BLCs) to the antibiotic market: ceftolozane-tazobactam, ceftazidime-avibactam, meropenem-vaborbactam, imipenem-relebactam, cefiderocol, and sulbactam-durlobactam. These agents are equipped with innovative mechanisms that confer broad Gram-negative activity, notably against certain challenging carbapenemases. While their introduction offers a beacon of hope, clinical microbiology laboratories must navigate the complexities of susceptibility testing for these agents due to their diverse activity profiles against specific β-lactamases and the possibility of acquired resistance mechanisms in some bacterial isolates. This review explores the complexities of these novel antimicrobial agents detailing the intricacies of their application, providing guidance on the nuances of susceptibility testing, interpretation, and result reporting in clinical microbiology laboratories.

Many modern applications of online changepoint detection require the ability to process high-frequency observations, sometimes with limited available computational resources. Online algorithms for detecting a change in mean often involve using a moving window, or specifying the expected size of change. Such choices affect which changes the algorithms have most power to detect. We introduce an algorithm, Functional Online CuSUM (FOCuS), which is equivalent to running these earlier methods simultaneously for all sizes of windows, or all possible values for the size of change. Our theoretical results give tight bounds on the expected computational cost per iteration of FOCuS, with this being logarithmic in the number of observations. We show how FOCuS can be applied to a number of different changes in mean scenarios, and demonstrate its practical utility through its state-of-the-art performance at detecting anomalous behaviour in computer server data. [ABSTRACT FROM AUTHOR]

Background: Balanced reciprocal translocation (BRT) is one of the most common chromosomal abnormalities that causes infertility, recurrent miscarriage, and birth defects. Preimplantation genetic testing (PGT) is widely used to select euploid embryos for BRT carriers to increase the chance of a healthy live birth. Several strategies can be used to distinguish reciprocal translocation carrier embryos from those with a normal karyotype; however, these techniques are time-consuming and difficult to implement in clinical laboratories. In this study, nanopore sequencing was performed in two reciprocal translocation carriers, and the results were validated using the next-generation sequencing-based method named, "Mapping Allele with Resolved Carrier Status" (MaReCs). Results: The translocation breakpoints in both reciprocal translocation carriers were accurately identified by nanopore sequencing and were in accordance with the results obtained using MaReCs. More than one euploid non-balanced translocation carrier embryo was identified in both patients. Amniocentesis results revealed normal karyotypes, consistent with the findings by MaReCs and nanopore sequencing. Conclusion: Our results suggest that nanopore sequencing is a powerful strategy for accurately distinguishing non-translocation embryos from translocation carrier embryos and precisely localizing translocation breakpoints, which is essential for PGT and aids in reducing the propagation of reciprocal translocation in the population. [ABSTRACT FROM AUTHOR]

While there are a plethora of algorithms for detecting changes in mean in univariate time-series, almost all struggle in real applications where there is autocorrelated noise or where the mean fluctuates locally between the abrupt changes that one wishes to detect. In these cases, default implementations, which are often based on assumptions of a constant mean between changes and independent noise, can lead to substantial over-estimation of the number of changes. We propose a principled approach to detect such abrupt changes that models local fluctuations as a random walk process and autocorrelated noise via an AR(1) process. We then estimate the number and location of changepoints by minimizing a penalized cost based on this model. We develop a novel and efficient dynamic programming algorithm, DeCAFS, that can solve this minimization problem; despite the additional challenge of dependence across segments, due to the autocorrelated noise, which makes existing algorithms inapplicable. Theory and empirical results show that our approach has greater power at detecting abrupt changes than existing approaches. We apply our method to measuring gene expression levels in bacteria. for this article are available online. [ABSTRACT FROM AUTHOR]

Warning: This article contains terms, descriptions, and opinions used for historical context that may be culturally sensitive for some readers. Background: Understanding drivers of boreal forest dynamics supports adaptation strategies in the context of climate change. Aims: We aimed to understand how burn rates varied since the early 1700s in North American boreal forests. Methods: We used 16 fire-history study sites distributed across such forests and investigated variation in burn rates for the historical period spanning 1700–1990. These were benchmarked against recent burn rates estimated for the modern period spanning 1980–2020 using various data sources. Key results: Burn rates during the historical period for most sites showed a declining trend, particularly during the early to mid 1900s. Compared to the historical period, the modern period showed less variable and lower burn rates across sites. Mean burn rates during the modern period presented divergent trends among eastern versus northwestern sites, with increasing trends in mean burn rates in most northwestern North American sites. Conclusions: The synchronicity of trends suggests that large spatial patterns of atmospheric conditions drove burn rates in addition to regional changes in land use like fire exclusion and suppression. Implications: Low burn rates in eastern Canadian boreal forests may continue unless climate change overrides the capacity to suppress fire. Warning: This article contains terms, descriptions, and opinions used for historical context that may be culturally sensitive for some readers. Our research highlights declining burn rates in North American boreal forests during 1700–1990 but rising burn rate trends at northwestern sites during 1980–2020. We suggest that atmospheric conditions and regional changes in land use like fire exclusion and suppression were important drivers behind the multi-century declining trend. [ABSTRACT FROM AUTHOR]

We examine the impacts of economic forces and fundamental variables on REIT returns. Our models endogenously select breakpoints to distinguish the heterogenous nature of the underlying properties with varying risk-return characteristics. Default risk premium and unanticipated inflation had an adverse effect, while GDP and federal funds rate had a positive effect on REITs. Market, size and value risk-premiums are significant for time periods that include the GFC but not for subsequent periods. Momentum is negative and significant for extreme events, and insignificant during calm periods. Higher beta values during the GFC followed by lower beta values confirm 'leveraging' and 'deleveraging' effects. [ABSTRACT FROM AUTHOR]

Background: Fetal skeletal dysplasia (SD) is a common congenital disability comprising a complex group of skeletal disorders with substantial clinical and genetic heterogeneity. Many of these defects are detected prenatally using ultrasound (US). However, the diagnostic accuracy of the US is limited.Methods: We recruited 55 unrelated fetuses with US-detected skeletal anomalies and performed sequential tests using copy number variation sequencing, targeted skeletal gene panel sequencing, or whole exome sequencing. The detected variants were validated using Sanger sequencing or multiplex ligation-dependent probe amplification. We conducted breakpoint analysis and structural modeling of variants possibly involved in fetal SD.Results: A definitive diagnosis was achieved in 81.82% of affected fetuses (45/55). We identified chromosomal abnormalities in seven cases and 36 variants, of which 18 were novel pathogenic or likely pathogenic in 11 genes in 38 cases. De novo variants were identified in 27 cases (71.05%, 27/38), and one gonosomal mosaicism variant was found in the mother of one fetus. Our case examples demonstrated the high heterogeneity of fetal SDs and the rare fetal SD-associated challenges.Conclusions: Careful clinical evaluation of fetuses with SD can guide appropriate molecular testing. Our study extends the SD-associated pathogenic variant spectrum and provides useful genetic counselling guidance and an accurate prenatal diagnosis strategy. [ABSTRACT FROM AUTHOR]

Antimicrobial resistance is a significant public health threat and a major challenge for treatment of companion animal skin infections. Antimicrobial susceptibility testing (AST) is a critical tool which clinicians should employ when a patient may need antimicrobials beyond those deemed "first-tier." Clinicians may have noted that many more isolates of Staphylococcus sp. and Pseudomonas aeruginosa appear more resistant which likely reflects both the emergence of acquired antimicrobial resistance, but also changes to clinical definitions which are outlined in this article., Competing Interests: Disclosure The author has nothing to disclose., (Copyright © 2024 Elsevier Inc. All rights reserved.)

ObjectiveAnemia is still an unfinished global health problem, and adverse birth weight outcomes have everlasting influences on the health of later life. However, the non-linear connections and breakpoints of maternal hemoglobin with birth weight outcomes are still needed to be further elucidated. We aimed to reveal the non-linear connections between maternal hemoglobin during the third trimester of pregnancy and birth weight, low birth weight (LBW), macrosomia, small for gestational age (SGA), and large for gestational age (LGA) in full-term newborns and elucidate the breakpoints of the connections.MethodsA total of 11,411 singletons, full-term, and live newborns, whose mothers conducted the examination of hemoglobin concentration before delivery, were included in this study. A generalized additive model was used to identify and visualize the non-linear connections between maternal hemoglobin and birth weight outcomes. Piecewise linear regression model was adopted to estimate the breakpoints of the connections and report the non-linear connections in detail.ResultsThere were inverted “U”-shaped exposure–response connections between maternal hemoglobin concentration and birth weight and the risk of macrosomia. There was an increasing trend of the risk of LBW and a decreased trend of LGA with the increase in maternal hemoglobin concentration. The breakpoints of maternal hemoglobin for birth weight were 100 and 138 g/L, and those for SGA were 97 and 138 g/L. The breakpoints of maternal hemoglobin were 119 g/L for LBW, 105 g/L for macrosomia, and 106 g/L for LGA. When maternal hemoglobin concentration ranged from 100 to 138 g/L, maternal hemoglobin concentration increased per 1 g/L, and birth weight significantly decreased by 2.58 g (95% CI: –3.33, –1.83). When maternal hemoglobin concentration ranged from 97 to 138 g/L, maternal hemoglobin concentration increased per 1 g/L, and the risk of SGA significantly increased by 2% (95% CI: 1%, 3%). When maternal hemoglobin concentration was equal to or lower than 119 g/L, maternal hemoglobin concentration increased per 1 g/L, and the risk of LBW significantly increased by 3% (95% CI: 0%, 5%). When maternal hemoglobin concentration was higher than the breakpoints, the risks of macrosomia (OR = 0.99, 95% CI: 0.98, 0.99) and LGA (OR = 0.99, 95% CI: 0.98, 1.00) declined as the increase of maternal hemoglobin concentration.ConclusionsThere were non-linear connections between maternal hemoglobin and birth weight outcomes, and there are breakpoints in the connections. Cost-effective interventions targeting pregnant women in the prevention of abnormal maternal hemoglobin concentration should be taken to reduce the incidence of adverse birth weight outcomes.

The Lubliner strength criterion (SC) can achieve desirable responses in the tension‐dominated and plane compressive stress states but overestimates the concrete strength under triaxial compression. Moreover, additional breakpoints without continuous derivatives occur along the hydrostatic pressure axis. The primary causes for these problems include the Lubliner SC constant γ parameter and breakpoints along the piecewise linear meridians. Therefore, a new Lubliner–Ottosen SC is developed with the parameter γ determined based on the Ottosen SC. The meridian contains smoothly connected straight and curved lines. Moreover, the deviatoric traces of the corresponding failure surface gradually change from curved triangles to approximate circles with increasing hydrostatic pressure. Finally, the proposed Lubliner–Ottosen SC is compared with other failure criteria and experimental results for concrete. Regardless of triaxial or nontriaxial compression, the new criterion can suitably represent the failure behavior of concrete in the various multiaxial stress states. [ABSTRACT FROM AUTHOR]

In January 2019, the European Committee for the Study of Antimicrobial Susceptibility (EUCAST) introduced some changes in the definitions of clinical categories for antibiotic susceptibility. The objective of these changes was to improve the credibility of category "I", optimizing and lengthening the survival and use of available antibiotics in the face of increasing antimicrobial resistance. This article aims to describe and explain these changes in the EUCAST criteria as well as make a short review about the factors on which the antibiotic susceptibility criteria depend. [ABSTRACT FROM AUTHOR]

Cefiderocol, a siderophore catechol cephalosporin, recently introduced in the market has been developed to enhance the in vitro activity of extended spectrum cephalosporins and to avoid resistance mechanisms affecting cephalosporins and carbapenems. The in vitro study of cefiderocol in the laboratory requires iron depleted media when MIC values are determined by broth microdilution. Disk diffusion presents good correlation with MIC values. In surveillance studies and in clinical trials it has been demonstrated excellent activity against Gram-negatives, including carbapenemase producers and non-fermenters such as Pseudomonas aeruginosa, Acinetobacter baumannii and Stenotrophomonas maltophilia. Few cefiderocol resistant isolates have been found in surveillance studies. Resistance mechanisms are not directly associated with porin deficiency and or efflux pumps. On the contrary, they are related with gene mutations affecting iron transporters, AmpC mutations in the omega loop and with certain beta-lactamases such us KPC-variants determining also ceftazidime-avibactam resistance, certain infrequent extended-spectrum betalactamases (PER, BEL) and metallo-beta-lactamases (certain NDM variants and SPM enzyme). [ABSTRACT FROM AUTHOR]

The scientific judgement of the structural abrupt transition characteristics of the carbon market price is an important means to comprehensively analyze its fluctuation law and effectively prevent carbon market risks. However, the existing methods for identifying structural changes of the carbon market based on carbon price data mostly regard the carbon price series as a deterministic time series and pay less attention to the uncertainty implied by the carbon price series. We propose a framework for identifying abrupt transitions in the carbon market from the perspective of a complex network by considering the influence of random factors on the carbon price series, expressing the carbon price series as a sequence of probability density functions, using the distribution of probability density to reveal the uncertainty information implied by carbon price series and constructing a recurrence network of carbon price probability density. Based on the community structure, the break index and statistical test method are defined. The simulation verifies the effectiveness and superiority of the method compared with traditional methods. An empirical analysis uses the carbon price data of the European Union carbon market and seven pilot carbon markets in China. The results show many abrupt transitions in the carbon price series of the two markets, whose occurrence period is closely related to major events. [ABSTRACT FROM AUTHOR]

Empirical evidence has been lacking to explain trade agglomerations within countries. Starting with a novel micro-database of road freight shipments between Spanish municipalities for the period 2003–07, we break down city (municipal) trade flows into the extensive and intensive margins and assess trade frictions and trade concentration relying on a unique generalized transport cost measure and three internal borders: NUTS-5 (municipal), NUTS-3 (provincial) and NUTS-2 (regional). We find a stark accumulation of trade flows up to a transport cost value of €189 (approximately 170 km) and conclude that this high density is not due to administrative borders effects but to significant changes in the trade-to-transport costs relationship. To support this hypothesis, we propose and conduct an endogenous Chow test to identify significant thresholds at which trade flows change structurally with transport costs. These breakpoints allow us to split the sample when controlling for internal borders, and to define trade market areas corresponding to specific transport costs that consistently reveal an urban hierarchy of cities. The results provide clear evidence with which to corroborate the predictions of Central Place Theory. [ABSTRACT FROM AUTHOR]

Urban ecological corridors are essential for sustainable urban development, but determining their width remains challenging. This paper addresses this issue by focusing on the unique habitat requirements of urban undercanopy bird species. We employ Species Distribution Model to simulate their potential living spaces in Shanghai and quantify their functional connectivity in urban mobility. We then use segmented linear regression models to identify turning points in functional connectivity within different buffer zones, which represent the physical width of the corridor. Our findings show that urban undercanopy birds are less sensitive to human activity and building distribution compared to surface temperature, land cover types, and vegetation canopy height. We also find that conventional linear weighting methods tend to overestimate the impact of environmental factors on undercanopy birds, leading to subtle deviations in corridor path recognition. Finally, we demonstrate that employing segmented linear regression helps to quantify the turning points of functional connectivity for each urban ecological corridor, allowing us to determine their physical width range. This study is the first attempt to quantitatively assess the functional connectivity of urban ecological corridors from the perspective of undercanopy birds and demarcate their extent. • Developed an urban ecological corridor construction process based on the perspective of understory birds. • Using circuit theory to simulate the potential movement paths and functional connectivity of forest birds in high-density cities. • Combining the functional connectivity of understory birds and piecewise linear regression model to identify the width of urban ecological corridors. • Identified the non-linear relationship between influencing factors on the habitat relationship of urban understory birds. [ABSTRACT FROM AUTHOR]

Understanding vegetation evolution is critical for exploring changes in terrestrial ecosystems and identifying future challenges. However, analyses that simultaneously examine trend shifts in vegetation greenness at the national, regional, biome, and pixel scales in China are still rare. Using long‐term (1982–2015) satellite data and the breaks for additive season and trend (BFAST) technique, we identified breakpoints in normalized difference vegetation index (NDVI) in China. The results showed that the annual mean NDVI gradually increased. A total of 68.8% of the vegetated area exhibited upward trends in NDVI, most of which was distributed in Southeast China and the Loess Plateau. Changes in NDVI trends occurred in 78.7% of the total vegetated areas, while hotspots were concentrated in Northwest and North China. A rapid increase in breakpoints was detected after 1999, mainly concentrated in North and Northwest China, and corresponding to the times and areas with the highest ecological engineering efforts. Positive shifts in NDVI trends were more common and generally distributed on the eastern side of the Hu Huanyong line, while browning (negative) shifts were mainly distributed on the western side and were gradually expanding, indicating a possible tendency toward environmental degradation. Although unstable vegetation areas that underwent land cover type changes had higher frequencies of breakpoints, the proportion of stable vegetation experiencing NDVI trend shifts was higher after 2000, probably because human intervention buffered external disturbances in unstable areas. Identifying hotspot areas of shifts in vegetation greenness can help setting priorities when taking measures for ecosystem conservation, thus provide scientific reference for sustainable land development. [ABSTRACT FROM AUTHOR]

Chromosomal inversions are widespread among taxa, and have been implicated in a number of biological processes including adaptation, sex chromosome evolution, and segregation distortion. Consistent with selection favoring linkage between loci, it is well established that length is a selected trait of inversions. However, the factors that affect the distribution of inversion breakpoints remain poorly understood. "Sensitive sites" have been mapped on all euchromatic chromosome arms in Drosophila melanogaster, and may be a source of natural selection on inversion breakpoint positions. Briefly, sensitive sites are genomic regions wherein proximal structural rearrangements result in large reductions in local recombination rates in heterozygotes. Here, I show that breakpoints of common inversions are significantly more likely to lie within a cytological band containing a sensitive site than are breakpoints of rare inversions. Furthermore, common inversions for which neither breakpoint intersects a sensitive site are significantly longer than rare inversions, but common inversions whose breakpoints intersect a sensitive site show no evidence for increased length. I interpret these results to mean that selection favors inversions whose breakpoints disrupt synteny near to sensitive sites, possibly because these inversions suppress recombination in large genomic regions. To my knowledge this is the first evidence consistent with positive selection acting on inversion breakpoint positions.