Going with the flow: Packed‐bed microreactors are formed from polymeric tubing and a resin‐supported catalyst. By using supported catalysts in flow systems, productivity and recycling are greatly ...improved. This approach can be used to couple multiple catalysts together for generating complex molecules in one flow‐through process.
The polymorphic inversion on 17q21, sometimes called the microtubular associated protein tau (MAPT) inversion, is an ∼900 kb inversion found primarily in Europeans and Southwest Asians. We have ...identified 21 SNPs that act as markers of the inverted, i.e., H2, haplotype. The inversion is found at the highest frequencies in Southwest Asia and Southern Europe (frequencies of ∼30%); elsewhere in Europe, frequencies vary from < 5%, in Finns, to 28%, in Orcadians. The H2 inversion haplotype also occurs at low frequencies in Africa, Central Asia, East Asia, and the Americas, though the East Asian and Amerindian alleles may be due to recent gene flow from Europe. Molecular evolution analyses indicate that the H2 haplotype originally arose in Africa or Southwest Asia. Though the H2 inversion has many fixed differences across the ∼900 kb, short tandem repeat polymorphism data indicate a very recent date for the most recent common ancestor, with dates ranging from 13,600 to 108,400 years, depending on assumptions and estimation methods. This estimate range is much more recent than the 3 million year age estimated by Stefansson et al. in 2005.1
Brexanolone is approved for postpartum depression (PPD) by the United States Food and Drug Administration. Brexanolone has outperformed placebo in clinical trials, but less is known about the ...efficacy in real-world patients with complex social and medical histories. Furthermore, the impact of brexanolone on large-scale brain systems such as changes in functional connectivity (FC) is unknown.
We tracked changes in depressive symptoms across a diverse group of patients who received brexanolone at a large medical center. Edinburgh Postnatal Depression Scale (EPDS) scores were collected through chart review for 17 patients immediately prior to infusion through approximately 1 year postinfusion. In 2 participants, we performed precision functional neuroimaging (pfMRI), including before and after treatment in 1 patient. pfMRI collects many hours of data in individuals for precision medicine applications and was performed to assess the feasibility of investigating changes in FC with brexanolone.
The mean EPDS score immediately postinfusion was significantly lower than the mean preinfusion score (mean change 95% CI: 10.76 7.11-14.40, t (15) = 6.29, P < 0.0001). The mean EPDS score stayed significantly lower at 1 week (mean difference 95% CI: 9.50 5.23-13.76, t (11) = 4.90, P = 0.0005) and 3 months (mean difference 95% CI: 9.99 4.71-15.27, t (6) = 4.63, P = 0.0036) postinfusion. Widespread changes in FC followed infusion, which correlated with EPDS scores.
Brexanolone is a successful treatment for PPD in the clinical setting. In conjunction with routine clinical care, brexanolone was linked to a reduction in symptoms lasting at least 3 months. pfMRI is feasible in postpartum patients receiving brexanolone and has the potential to elucidate individual-specific mechanisms of action.
The hippocampus is critically important for a diverse range of cognitive processes, such as episodic memory, prospective memory, affective processing, and spatial navigation. Using ...individual-specific precision functional mapping of resting-state functional MRI data, we found the anterior hippocampus (head and body) to be preferentially functionally connected to the default mode network (DMN), as expected. The hippocampal tail, however, was strongly preferentially functionally connected to the parietal memory network (PMN), which supports goal-oriented cognition and stimulus recognition. This anterior-posterior dichotomy of resting-state functional connectivity was well-matched by differences in task deactivations and anatomical segmentations of the hippocampus. Task deactivations were localized to the hippocampal head and body (DMN), relatively sparing the tail (PMN). The functional dichotomization of the hippocampus into anterior DMN-connected and posterior PMN-connected parcels suggests parallel but distinct circuits between the hippocampus and medial parietal cortex for self- versus goal-oriented processing.
Global importance of large-diameter trees Lutz, James A.; Furniss, Tucker J.; Johnson, Daniel J. ...
Global ecology and biogeography,
July 2018, Letnik:
27, Številka:
7/8
Journal Article
Recenzirano
Odprti dostop
Aim: To examine the contribution of large-diameter trees to biomass, stand structure, and species richness across forest biomes. Location: Global. Time period: Early 21st century. Major taxa studied: ...Woody plants. Methods: We examined the contribution of large trees to forest density, richness and biomass using a global network of 48 large (from 2 to 60 ha) forest plots representing 5,601,473 stems across 9,298 species and 210 plant families. This contribution was assessed using three metrics: the largest 1% of trees ≥ 1 cm diameter at breast height (DBH), all trees ≥ 60 cm DBH, and those rank-ordered largest trees that cumulatively comprise 50% of forest biomass. Results: Averaged across these 48 forest plots, the largest 1% of trees ≥ 1 cm DBH comprised 50% of aboveground live biomass, with hectare-scale standard deviation of 26%. Trees ≥ 60 cm DBH comprised 41% of aboveground live tree biomass. The size of the largest trees correlated with total forest biomass (r2 = .62, p < .001). Large-diameter trees in high biomass forests represented far fewer species relative to overall forest richness (r2 = .45, p < .001). Forests with more diverse large-diameter tree communities were comprised of smaller trees (r2 = .33, p < .001). Lower large-diameter richness was associated with large-diameter trees being individuals of more common species (r2 = .17, p = .002). The concentration of biomass in the largest 1% of trees declined with increasing absolute latitude (r2 = .46, p < .001), as did forest density (r2 = .31, p < .001). Forest structural complexity increased with increasing absolute latitude (r2 = .26, p < .001). Main conclusions: Because large-diameter trees constitute roughly half of the mature forest biomass worldwide, their dynamics and sensitivities to environmental change represent potentially large controls on global forest carbon cycling. We recommend managing forests for conservation of existing large-diameter trees or those that can soon reach large diameters as a simple way to conserve and potentially enhance ecosystem services.
Single nucleotide polymorphisms (SNPs) are likely in the near future to have a fundamental role in forensics in both human identification and description. However, considerable research is necessary ...to establish adequate scientific foundations for these applications. In the case of identification, because allele frequencies can vary greatly among populations, the population genetics of match probabilities is a critical issue. Some SNPs, however, show little allele frequency variation among populations while remaining highly informative. We describe here both an efficient strategy for identifying and characterizing such SNPs, and test that strategy on a broad representation of world populations. Markers with high heterozygosity and little frequency variation among African American, European American, and East Asian populations are selected for additional screening on seven populations that provide a sampling of genetic variation from the world's major geographical regions. Those with little allele frequency variation on the seven populations are then screened on a total of 40 populations (∼2100 individuals) and the most promising retained. The preliminary panel of 19 SNPs, from an initial selection of 195 SNPs, gives an average match probability of <10
−7 in most of 40 populations studied and no greater than 10
−6 in the most isolated, inbred populations. Expansion of this panel to ∼50 comparable SNPs should give match probabilities of about 10
−15 with a small global range.
Cladribine is a purine nucleoside analog initially developed in the 1970s as a treatment for various blood cancers. Due to the molecule’s ability to preferentially reduce T and B lymphocytes, it has ...been developed into an oral formulation for the treatment of multiple sclerosis (MS). The unique proposed mechanism of action of cladribine allows for the therapy to be delivered orally over two treatment-week cycles per year, one cycle at the beginning of the first month and one cycle at the beginning of the second month of years 1 and 2, with the potential for no further cladribine treatment required in years 3 and 4. This review summarizes the clinical development program for cladribine tablets in patients with MS, including the efficacy endpoints and results from the 2-year phase III CLARITY study in patients with relapsing–remitting MS (RRMS), the 2-year CLARITY EXTENSION study, and the phase III ORACLE-MS study in patients with a first clinical demyelinating event at risk for developing MS. Efficacy results from the phase II ONWARD study, in which cladribine tablets were administered as an add-on to interferon-β therapy in patients with RRMS, are also summarized. A review of all safety data, including lymphopenia, infections, and malignancies, is provided based on data from all trials in patients with MS, including the initial parenteral formulation studies. Based on these data, cladribine tablets administered at 3.5 mg/kg over 2 years have been approved across the globe for various forms of relapsing MS.
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The development of cladribine tablets for the treatment of multiple sclerosis: a comprehensive review (MP4 279143 kb)
Cardiopulmonary exercise testing (CPET) has become an invaluable tool in healthcare, improving the diagnosis of disease and the quality, efficacy, assessment and safety of treatment across a range of ...pathologies. CPET’s superior ability to measure the global exercise response of the respiratory, cardiovascular and skeletal muscle systems simultaneously in a time and cost-efficient manner has led to the application of CPET in a range of settings from diagnosis of disease to preoperative assessment. The Association for Respiratory Technology and Physiology Statement on Cardiopulmonary Exercise Testing 2021 provides the practitioner and scientist with an outstanding resource to support and enhance practice, from equipment to testing to leadership, helping them deliver a quality assured service for the benefit of all patient groups.
The goal of precision medicine (individually tailored treatments) is not being achieved for neurobehavioural conditions such as psychiatric disorders. Traditional randomized clinical trial methods ...are insufficient for advancing precision medicine because of the dynamic complexity of these conditions. We present a pragmatic solution: the precision clinical trial framework, encompassing methods for individually tailored treatments. This framework includes the following: (1) treatment-targeted enrichment, which involves measuring patients' response after a brief bout of an intervention, and then randomizing patients to a full course of treatment, using the acute response to predict long-term outcomes; (2) adaptive treatments, which involve adjusting treatment parameters during the trial to individually optimize the treatment; and (3) precise measurement, which involves measuring predictor and outcome variables with high accuracy and reliability using techniques such as ecological momentary assessment. This review summarizes precision clinical trials and provides a research agenda, including new biomarkers such as precision neuroimaging, transcranial magnetic stimulation-electroencephalogram digital phenotyping and advances in statistical and machine-learning models. Validation of these approaches - and then widespread incorporation of the precision clinical trial framework - could help achieve the vision of precision medicine for neurobehavioural conditions.
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