•The Great Barrier Reef’s biodiversity is under threat from multiple pressures.•Port and shipping activities are escalating, and present a new management challenge.•We review the impacts of ports and ...shipping on biodiversity.•We also identify principles to improve the governance of port and shipping impacts.•Change can avoid the Reef being added to the List of World Heritage in Danger.
The Great Barrier Reef (GBR) region of Queensland, Australia, encompasses a complex and diverse array of tropical marine ecosystems of global significance. The region is also a World Heritage Area and largely within one of the world’s best managed marine protected areas. However, a recent World Heritage Committee report drew attention to serious governance problems associated with the management of ports and shipping. We review the impacts of ports and shipping on biodiversity in the GBR, and propose a series of guiding principles to improve the current governance arrangements. Implementing these principles will increase the capacity of decision makers to minimize the impacts of ports and shipping on biodiversity, and will provide certainty and clarity to port operators and developers. A ‘business as usual’ approach could lead to the GBR’s inclusion on the List of World Heritage in Danger in 2014.
Intellectual disability (ID) is a clinically and genetically heterogeneous disorder, affecting 1-3% of the general population. Although research into the genetic causes of ID has recently gained ...momentum, identification of pathogenic mutations that cause autosomal recessive ID (ARID) has lagged behind, predominantly due to non-availability of sizeable families. Here we present the results of exome sequencing in 121 large consanguineous Pakistani ID families. In 60 families, we identified homozygous or compound heterozygous DNA variants in a single gene, 30 affecting reported ID genes and 30 affecting novel candidate ID genes. Potential pathogenicity of these alleles was supported by co-segregation with the phenotype, low frequency in control populations and the application of stringent bioinformatics analyses. In another eight families segregation of multiple pathogenic variants was observed, affecting 19 genes that were either known or are novel candidates for ID. Transcriptome profiles of normal human brain tissues showed that the novel candidate ID genes formed a network significantly enriched for transcriptional co-expression (P<0.0001) in the frontal cortex during fetal development and in the temporal-parietal and sub-cortex during infancy through adulthood. In addition, proteins encoded by 12 novel ID genes directly interact with previously reported ID proteins in six known pathways essential for cognitive function (P<0.0001). These results suggest that disruptions of temporal parietal and sub-cortical neurogenesis during infancy are critical to the pathophysiology of ID. These findings further expand the existing repertoire of genes involved in ARID, and provide new insights into the molecular mechanisms and the transcriptome map of ID.
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•MnCoxNixFe2−2xO4 nanoferrites were synthesized by co-precipitation technique.•The crystallite size is found in the range 27–35 nm.•The saturation magnetization was raised up to ...52 emu/g.•These ferrites may have potential applications in switching applications.
In this study Co-Ni co-doped nanocrystalline manganese ferrites were fabricated via co-precipitation method. The annealing of as prepared nanoferrites was done at 950 °C for 7 h. The powder X-ray diffraction (XRD) confirmed that all samples possessed cubic spinel structure. The crystallite size was determined by Scherrer’s equation that lies in the range of 27–35 nm. The spectral analysis confirmed bending and stretching of bonds at octahedral (B) and tetrahedral (A) sites. The spectral bands were shifted towards the longer wavelength side and these indicate the incorporation of dopants cations (Co-Ni). The magnetic parameters were measured from the M-H loops of nanoferrites. With the increase of Co-Ni contents, the saturation magnetization (Ms) increased up to x = 0.15 and then it decreased. The dielectric properties of all compositions were studied in 1 MHz–3 GHz range and were discussed in the light of Debye-type reduction phenomenon by following the Koop’s theory. The dielectric and magnetic behavior evaluation suggested that synthesized ferrites are suitable for microwave devices fabrication.
Summary Background A previous study in Pakistan assessed the effectiveness of delivering responsive stimulation and enhanced nutrition interventions to young children. Responsive stimulation ...significantly improved children's cognitive, language, and motor development at 2 years of age. Both interventions significantly improved parenting skills, with responsive stimulation showing larger effects. In this follow-up study, we investigated whether interventions had benefits on children's healthy development and care at 4 years of age. Methods We implemented a follow-up study of the initial, community-based cluster-randomised effectiveness trial, which was conducted through the Lady Health Worker programme in Sindh, Pakistan. We re-enrolled 1302 mother–child dyads (87% of the 1489 dyads in the original enrolment) for assessment when the child was 4 years of age. The children were originally randomised in the following groups: nutrition education and multiple micronutrient powders (enhanced nutrition; n=311), responsive stimulation (n=345), combined responsive stimulation and enhanced nutrition (n=315), and routine health and nutrition services (control; n=331). The data collection team were masked to the allocated intervention. The original enrolment period included children born in the study area between April 1, 2009, and March 31, 2010, if they were up to 2·5 months old without signs of severe impairments. The primary endpoints for children were development and growth at 4 years of age. Interventions were given in monthly group sessions and in home visits. The primary endpoint for mothers was wellbeing and caregiving knowledge, practices, and skills when the child was 4 years of age. Analysis was by intention to treat. The original trial is registered with ClinicalTrials.gov , number NCT00715936. Findings 1302 mother–child dyads were re-enrolled between Jan 1, 2013, and March 31, 2013, all of whom were followed up at 4 years of age. Children who received responsive stimulation (with or without enhanced nutrition) had significantly higher cognition, language, and motor skills at 4 years of age than children who did not receive responsive stimulation. For children who received responsive stimulation plus enhanced nutrition, effect sizes (Cohen's d) were 0·1 for IQ (mean difference from control 1·2, 95% CI −0·3 to 2·7), 0·3 for executive functioning (0·18, −0·07 to 0·29), 0·5 for pre-academic skills (7·53, 5·14 to 9·92) and 0·2 for pro-social behaviours (0·08, 0·03 to 0·13). For children who received responsive stimulation alone, effect sizes were 0·1 for IQ (mean difference with controls 1·7, −0·3 to 3·7), 0·3 for executive functioning (0·17, 0·07 to 0·27), 0·2 for pre-academic skills (3·86, 1·41 to 6·31), and 0·2 for pro-social behaviours (0·07, 0·02 to 0·12). Enhanced nutrition improved child motor development, with effect size of 0·2 for responsive stimulation plus enhanced nutrition (0·56, −0·03 to 1·15), and for enhanced nutrition alone (0·82, 0·18 to 1·46). Mothers who received responsive stimulation (with or without enhanced nutrition) had significantly better responsive caregiving behaviours at 4 years of child age than those who did not receive intervention. Effect size was 0·3 for responsive stimulation plus enhanced nutrition (1·95, 0·75 to 3·15) and 0·2 for responsive stimulation (2·01, 0·74 to 3·28). The caregiving environment had a medium effect size of 0·3 for all interventions (responsive stimulation plus enhanced nutrition 2·99, 1·50 to 4·48; responsive stimulation alone 2·82, 1·21 to 4·43; enhanced nutrition 3·52, 1·70 to 5·34). Interpretation Responsive stimulation delivered in a community health service can improve child development and care, 2 years after the end of intervention. Future analyses of these data are needed to identify which children and families benefit more or less over time. Funding Grand Challenges Canada.
Cyclin-dependent kinase 9 (CDK9) plays a critical role in transcriptional elongation, through which short-lived antiapoptotic proteins are overexpressed and make cancer cells resistant to apoptosis. ...Therefore, CDK9 inhibition depletes antiapoptotic proteins, which in turn leads to the reinstatement of apoptosis in cancer cells. Twenty-seven compounds were synthesized, and their CDK9 inhibitory and cytotoxic activities were evaluated. Compounds
,
, and
were the most potent CDK9 inhibitors, with
values of 0.115, 0.131, and 0.142 μM, respectively. The binding modes of these molecules were studied via molecular docking, which shows that they occupy the adenosine triphosphate binding site of CDK9. Of these three molecules, compound
shows good drug-like properties, as it does not violate Lipinski's rule of five. In addition, this molecule shows promising ligand and lipophilic efficiency values and is an ideal candidate for further optimization.
This study investigates the moderating roles of environmental munificence and dynamism in the relationship between process rationality and organizational performance. Based on a sample of 62 ...manufacturing firms, the study found that environmental munificence and dynamism moderate the relationship between rationality and performance. Further, the study found that rationality is strongly associated with performance in environments high in munificence and dynamism.
Various vision-threatening eye diseases including age-related macular degeneration (AMD) and central serous chorioretinopathy (CSCR) are caused due to the dysfunctions manifested in the highly ...vascular choroid layer of the posterior segment of the eye. In the current clinical practice, screening choroidal structural changes is widely based on optical coherence tomography (OCT) images. Accordingly, to assist clinicians, several automated choroidal biomarker detection methods using OCT images are developed. However, the performance of these algorithms is largely constrained by the quality of the OCT scan. Consequently, determining the quality of choroidal features in OCT scans is significant in building standardized quantification tools and hence constitutes our main objective. This study includes a dataset of 1593 good and 2581 bad quality Spectralis OCT images graded by an expert. Noting the efficacy of deep-learning (DL) in medical image analysis, we propose to train three state-of-the-art DL models: ResNet18, EfficientNet-B0 and EfficientNet-B3 to detect the quality of OCT images. The choice of these models was inspired by their ability to preserve the salient features across all the layers without information loss. To evaluate the attention of DL models on the choroid, we introduced color transparency maps (CTMs) based on GradCAM explanations. Further, we proposed two subjective grading scores: overall choroid coverage (OCC) and choroid coverage in the visible region(CCVR) based on CTMs to objectively correlate visual explanations vis-à-vis DL model attentions. We observed that the average accuracy and F-scores for the three DL models are greater than 96%. Further, the OCC and CCVR scores achieved for the three DL models under consideration substantiate that they mostly focus on the choroid layer in making the decision. In particular, of the three DL models, EfficientNet-B3 is in close agreement with the clinician's inference. The proposed DL-based framework demonstrated high detection accuracy as well as attention on the choroid layer, where EfficientNet-B3 reported superior performance. Our work assumes significance in bench-marking the automated choroid biomarker detection tools and facilitating high-throughput screening. Further, the methods proposed in this work can be adopted for evaluating the attention of DL-based approaches developed for other region-specific quality assessment tasks.
Domestic donkey plays a key role as a draft animal in rural economy of Pakistan where its population is increasing every year. The complete mtDNA control region of forty randomly sampled donkeys was ...PCR- amplified and sequenced bi-directionally using specific primers. Distinct mtDNA haplotypes obtained in the current study (KY446001-KY446011) were subjected to haplotype (h) and nucleotide diversity (π) measures using DnaS as well as to phylogenetic, Network, and AMOVA analyses. There were a total 27 polymorphic sites present within 11 unique mtDNA haplotypes from the studied 40 animals from different regions. Neighbor-joining network and median-joining network both illustrated the splitting of all these haplotypes into two well-defined Nubian and Somali lineages, confirming African maternal origin of Pakistani domestic donkey. Diversity parameters h (0.967± 0.037) and π (0.02917± 0.00307) were found to reveal high levels of genetic diversity in Pakistani donkeys. AMOVA demonstrated only 1% of genetic differences between two mtDNA maternal lineages, pointing to lack of population substructure in Pakistani donkeys as is the case with worldwide domestic donkey population. Pakistani donkeys have African maternal origin and high levels of mtDNA diversity. High genetic diversity may be due to non-selective breeding and heteroplasmy. We herein provide the first report on mtDNA diversity of control region in Pakistani domestic donkey.
•Carnitine palmitoyl transferase II (CPT II) deficiency is a rare disorder of fatty acid metabolism.•Complications of general anaesthesia have been described.•Regional or neuraxial anaesthesia is ...usually advised.•Prolonged spinal anaesthesia is described in a patient with CPT II deficiency.
Carnitine palmitoyl transferase II (CPT II) deficiency is a rare disorder of fatty acid metabolism in cell mitochondria. There is limited information about the disease process and complications of anaesthesia, particularly in the obstetric population. Due to the increased risks of general anaesthesia in patients with CPT II deficiency, neuraxial anaesthesia is the preferred method of anaesthesia. We describe a patient with CPT II deficiency who had spinal anaesthesia for caesarean section. Subsequently, the patient had prolonged neuraxial blockade, a previously undescribed complication in a patient with CPT II deficiency.
In this computational work, with the aim of boosting the ultimate efficiency of organic photovoltaic cells, seven small acceptors (
IDST1-IDST7
) were proposed by altering the terminal-acceptors of ...reference molecule
IDSTR
. The optoelectronic characteristics of the
IDSTR
and
IDST1-IDST7
molecules were investigated using the MPW1PW91/6-31G(d,p) level of theory, and solvent-state computations were examined using time-dependent density functional theory (TD-DFT) simulation. Nearly all the investigated photovoltaic aspects of the newly proposed molecules were found to be better than those of the
IDSTR
molecule
e.g.
in comparison to
IDSTR
,
IDST1-IDST7
exhibit a narrower bandgap (
E
gap
), lower first excitation energy (
E
x
), and a significant red-shift in the absorbance maxima (
λ
max
). According to the findings,
IDST3
has the lowest
E
x
(1.61 eV), the greatest
λ
max
(770 nm), and the shortest
E
gap
(2.09 eV).
IDST1-IDST7
molecules have higher electron mobility because their RE of electrons is less than that of
IDSTR
. Hole mobility of
IDST2-IDST7
is higher than that of the reference owing to their lower RE for hole mobility than
IDSTR
. By coupling with the PTB7-Th donor, the open circuit voltage (
V
OC
) of the investigated acceptor molecules (
IDSTR
and
IDST1-IDST7
) was calculated and investigation revealed that
IDST4-IDST6
molecules showed higher
V
OC
and fill factor (FF) values than
IDSTR
molecules. Accordingly, the modified molecules can be seriously evaluated for actual use in the fabrication of OSCs with enhanced photovoltaic and optoelectronic characteristics in light of the findings of this study.
In this work, with the aim of boosting the ultimate efficiency of organic solar cells, seven small acceptor molecules (
IDST1-IDST7
) were proposed by altering the terminal-acceptor of reference molecule
IDSTR
.
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