Until recently, most of energy and industrially produced chemicals were derived from fossil fuel-based resources. This along with the continued depletion of finite fossil resources and their ...attributed adverse environmental impacts, alternatively sourced and more sustainable resources are being pursued as feedstock replacements. Thus, biomass has been identified as an alternate renewable and more sustainable resource as a means to reduce this sector’s dependence on fossil fuel-based resources and to alleviate their environmental impacts. As such, lignocellulosic biomass has been further identified and demonstrated as an abundant renewable resource for the production of biofuels, platform chemicals, and their respective value-added products. This review article provides an overview of the techniques developed for the valorization of biomass in the production of platform chemicals within a biorefinery and the status for commercialization.
We review the literature on organizational climate and culture paying specific attention to articles published in the Journal of Applied Psychology (JAP) since its first volume in 1917. The article ...traces the history of the 2 constructs though JAP has been far more important for climate than culture research. We distinguish 4 main periods: the pre-1971 era, with pioneering work on exploring conceptualization and operationalizations of the climate construct; the 1971-1985 era, with foundational work on aggregation issues, outcome-focused climates (on safety and service) and early writings on culture; the 1986-1999 era, characterized by solidification of a focused climate approach to understanding organizational processes (justice, discrimination) and outcomes (safety, service) and the beginnings of survey approaches to culture; and the 2000-2014 era, characterized by multilevel work on climate, climate strength, demonstrated validity for a climate approach to outcomes and processes, and the relationship between leadership and climate and culture. We summarize and comment on the major theory and research achievements in each period, showing trends observed in the literature and how JAP has contributed greatly to moving research on these constructs, especially climate, forward. We also recommend directions for future research given the current state of knowledge.
There is a great unmet need for advanced therapies that provide rapid, robust, and sustained disease control for patients with ulcerative colitis. We assessed the efficacy and safety of upadacitinib, ...an oral selective Janus kinase 1 inhibitor, as induction and maintenance therapy in patients with moderately to severely active ulcerative colitis.
This phase 3, multicentre, randomised, double-blind, placebo-controlled clinical programme consisted of two replicate induction studies (U-ACHIEVE induction UC1 and U-ACCOMPLISH UC2) and a single maintenance study (U-ACHIEVE maintenance UC3). The studies were conducted across Europe, North and South America, Australasia, Africa, and the Asia-Pacific region at 199 clinical centres in 39 countries (UC1), 204 clinical centres in 40 countries (UC2), and 195 clinical centres in 35 countries (UC3). Patients aged 16–75 years with moderately to severely active ulcerative colitis (Adapted Mayo score 5–9; endoscopic subscore 2 or 3) for at least 90 days were randomly assigned (2:1) to oral upadacitinib 45 mg once daily or placebo for 8 weeks (induction studies). Patients who achieved clinical response following 8-week upadacitinib induction were re-randomly assigned (1:1:1) to upadacitinib 15 mg, upadacitinib 30 mg, or placebo for 52 weeks (maintenance study). All patients were randomly assigned using web-based interactive response technology. The primary endpoints were clinical remission per Adapted Mayo score at week 8 (induction) and week 52 (maintenance). The efficacy analyses in the two induction studies were based on the intent-to-treat population, which included all randomised patients who received at least one dose of treatment. In the maintenance study, the primary efficacy analyses reported in this manuscript were based on the first 450 (planned) clinical responders to 8-week induction therapy with upadacitinib 45 mg once daily. The safety analysis population in the induction studies consisted of all randomised patients who received at least one dose of treatment; in the maintenance study, this population included all patients who received at least one dose of treatment as part of the primary analysis population. These studies are registered at ClinicalTrials.gov, NCT02819635 (U-ACHIEVE) and NCT03653026 (U-ACCOMPLISH).
Between Oct 23, 2018, and Sept 7, 2020, 474 patients were randomly assigned to upadacitinib 45 mg once daily (n=319) or placebo (n=155) in UC1. Between Dec 6, 2018, and Jan 14, 2021, 522 patients were randomly assigned to upadacitinib 45 mg once daily (n=345) or placebo (n=177) in UC2. In UC3, a total of 451 patients (21 from the phase 2b study, 278 from UC1, and 152 from UC2) who achieved a clinical response after 8 weeks of upadacitinib induction treatment were randomly assigned again to upadacitinib 15 mg (n=148), upadacitinib 30 mg (n=154), and placebo (n=149) in the primary analysis population. Statistically significantly more patients achieved clinical remission with upadacitinib 45 mg (83 26% of 319 patients in UC1 and 114 34% of 341 patients in UC2) than in the placebo group (seven 5% of 154 patients in UC1 and seven 4% of 174 patients; p<0·0001; adjusted treatment difference 21·6% 95% CI 15·8–27·4 for UC1 and 29·0% 23·2–34·7 for UC2). In the maintenance study, clinical remission was achieved by statistically significantly more patients receiving upadacitinib (15 mg 63 42% of 148; 30 mg 80 52% of 154) than those receiving placebo (18 12% of 149; p<0·0001; adjusted treatment difference 30·7% 21·7–39·8 for upadacitinib 15 mg vs placebo and 39·0% 29·7–48·2 for upadacitinib 30 mg vs placebo). The most commonly reported adverse events in UC1 were nasopharyngitis (15 5% of 319 in the upadacitinib 45 mg group vs six 4% of 155 in the placebo group), creatine phosphokinase elevation (15 4% vs three 2%), and acne (15 5% vs one 1%). In UC2, the most frequently reported adverse event was acne (24 7% of 344 in the upadacitinib 45 mg group vs three 2% of 177 in the placebo group). In both induction studies, serious adverse events and adverse events leading to discontinuation of treatment were less frequent in the upadacitinib 45 mg group than in the placebo group (serious adverse events eight 3% vs nine (6%) in UC1 and 11 3% vs eight 5% in UC2; adverse events leading to discontinuation six 2% vs 14 9% in UC1 and six 2% vs nine 5% in UC2). In UC3, the most frequently reported adverse events (≥5%) were worsening of ulcerative colitis (19 13% of 148 in the upadacitinib 15 mg group vs 11 7% of 154 in the upadacitinib 30 mg group vs 45 30% of 149 in the placebo group), nasopharyngitis (18 12% vs 22 14% vs 15 10%), creatine phosphokinase elevation (nine 6% vs 13 8% vs three 2%), arthralgia (nine 6% vs five 3% vs 15 10%), and upper respiratory tract infection (seven 5% vs nine 6% vs six 4%). The proportion of serious adverse events (ten 7% vs nine 6% vs 19 13%) and adverse events leading to discontinuation (six 4% vs ten 6% vs 17 11%) was lower in both upadacitinib groups than in the placebo group. Events of cancer, adjudicated major adverse cardiac events, or venous thromboembolism were reported infrequently. There were no treatment-related deaths.
Upadacitinib demonstrated a positive efficacy and safety profile and could be an effective treatment option for patients with moderately to severely active ulcerative colitis.
AbbVie.
Correctly staging lung cancer is important because the treatment options and prognosis differ significantly by stage. Several noninvasive imaging studies and invasive tests are available. ...Understanding the accuracy, advantages, and disadvantages of the available methods for staging non-small cell lung cancer is critical to decision-making.
Test accuracies for the available staging studies were updated from the second iteration of the American College of Chest Physicians Lung Cancer Guidelines. Systematic searches of the MEDLINE database were performed up to June 2012 with the inclusion of selected meta-analyses, practice guidelines, and reviews. Study designs and results are summarized in evidence tables.
The sensitivity and specificity of CT scanning for identifying mediastinal lymph node metastasis were approximately 55% and 81%, respectively, confirming that CT scanning has limited ability either to rule in or exclude mediastinal metastasis. For PET scanning, estimates of sensitivity and specificity for identifying mediastinal metastasis were approximately 77% and 86%, respectively. These findings demonstrate that PET scanning is more accurate than CT scanning, but tissue biopsy is still required to confirm PET scan findings. The needle techniques endobronchial ultrasound-needle aspiration, endoscopic ultrasound-needle aspiration, and combined endobronchial ultrasound/endoscopic ultrasound-needle aspiration have sensitivities of approximately 89%, 89%, and 91%, respectively. In direct comparison with surgical staging, needle techniques have emerged as the best first diagnostic tools to obtain tissue. Based on randomized controlled trials, PET or PET-CT scanning is recommended for staging and to detect unsuspected metastatic disease and avoid noncurative resections.
Since the last iteration of the staging guidelines, PET scanning has assumed a more prominent role both in its use prior to surgery and when evaluating for metastatic disease. Minimally invasive needle techniques to stage the mediastinum have become increasingly accepted and are the tests of first choice to confirm mediastinal disease in accessible lymph node stations. If negative, these needle techniques should be followed by surgical biopsy. All abnormal scans should be confirmed by tissue biopsy (by whatever method is available) to ensure accurate staging. Evidence suggests that more complete staging improves patient outcomes.
With a political debate about the potential risks and benefits of cannabis use as a backdrop, the wave of legalization and liberalization initiatives continues to spread. Four states (Colorado, ...Washington, Oregon, and Alaska) and the District of Columbia have passed laws that legalized cannabis for recreational use by adults, and 23 others plus the District of Columbia now regulate cannabis use for medical purposes. These policy changes could trigger a broad range of unintended consequences, with profound and lasting implications for the health and social systems in our country. Cannabis use is emerging as one among many interacting factors that can affect brain development and mental function. To inform the political discourse with scientific evidence, the literature was reviewed to identify what is known and not known about the effects of cannabis use on human behavior, including cognition, motivation, and psychosis.
Many types of slippery liquid‐infused porous surfaces (‘SLIPS’) can resist adhesion and colonization by microorganisms. These ‘slippery’ materials thus offer approaches to prevent fouling on ...commercial and industrial surfaces. However, while SLIPS can prevent fouling on surfaces to which they are applied, they can currently do little to prevent the proliferation of non‐adherent organisms. Here, multi‐functional SLIPS are reported that address this issue and expand the potential utility of these materials. The approach is based on the release of antimicrobial agents from the porous matrices used to host the infused oil phases. It is demonstrated that SLIPS fabricated from nanoporous polymer multilayers can prevent colonization and biofilm formation by four common fungal and bacterial pathogens, and that the polymer and oil phases comprising these materials can be used to sustain the release of triclosan, a model antimicrobial agent, into surrounding media. This approach improves the inherent anti‐fouling properties of these materials and endows them with the ability to kill non‐adherent pathogens. This strategy has the potential to be general; the strategies and concepts reported here will enable the design of SLIPS with improved anti‐fouling properties and open the door to new applications of slippery liquid‐infused materials that host or release other active agents.
Slippery, liquid‐infused porous surfaces (SLIPS) that prevent colonization by microbial pathogens and also kill non‐adherent organisms in surrounding media are reported. The approach exploits the polymer and liquid phases in these materials to sustain the release of an antimicrobial agent. This approach improves the inherent anti‐fouling properties of SLIPS, is general in scope, and expands the potential utility of SLIPS in fundamental and applied contexts.
The Myogenic Regulatory Factors (MRFs) Myf5, MyoD, myogenin and MRF4 are members of the basic helix-loop-helix family of transcription factors that control the determination and differentiation of ...skeletal muscle cells during embryogenesis and postnatal myogenesis. The dynamics of their temporal and spatial expression as well as their biochemical properties have allowed the identification of a precise and hierarchical relationship between the four MRFs. This relationship establishes the myogenic lineage as well as the maintenance of the terminal myogenic phenotype. The application of genome-wide technologies has provided important new information as to how the MRFs function to activate muscle gene expression. Application of combined functional genomics technologies along with single cell lineage tracing strategies will allow a deeper understanding of the mechanisms mediating myogenic determination, cell differentiation and muscle regeneration.
Hematopoietic stem cells (HSCs) mediate regeneration of the hematopoietic system following injury, such as following infection or inflammation. These challenges impair HSC function, but whether this ...functional impairment extends beyond the duration of inflammatory exposure is unknown. Unexpectedly, we observed an irreversible depletion of functional HSCs following challenge with inflammation or bacterial infection, with no evidence of any recovery up to 1 year afterward. HSCs from challenged mice demonstrated multiple cellular and molecular features of accelerated aging and developed clinically relevant blood and bone marrow phenotypes not normally observed in aged laboratory mice but commonly seen in elderly humans. In vivo HSC self-renewal divisions were absent or extremely rare during both challenge and recovery periods. The progressive, irreversible attrition of HSC function demonstrates that temporally discrete inflammatory events elicit a cumulative inhibitory effect on HSCs. This work positions early/mid-life inflammation as a mediator of lifelong defects in tissue maintenance and regeneration.
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•HSCs fail to recover functional potency after inflammatory/infection challenge•Discrete challenges have a cumulative effect, even if separated by weeks or months•Inflammation in early life accelerates the cellular and molecular aging of HSCs•Mice exposed to inflammation develop features of aged human hematopoiesis
Inflammation and infection acutely suppress HSC function. However, the long-term ramifications of such challenges are unclear. This study demonstrates that murine HSCs fail to recover functional potency up to 1 year post-inflammatory/infection challenge, meaning that such events can have accumulative effects over a lifetime; this promotes acquisition of the aged state.
Spastic paraplegia 46 refers to a locus mapped to chromosome 9 that accounts for a complicated autosomal-recessive form of hereditary spastic paraplegia (HSP). With next-generation sequencing in ...three independent families, we identified four different mutations in GBA2 (three truncating variants and one missense variant), which were found to cosegregate with the disease and were absent in controls. GBA2 encodes a microsomal nonlysosomal glucosylceramidase that catalyzes the conversion of glucosylceramide to free glucose and ceramide and the hydrolysis of bile acid 3-O-glucosides. The missense variant was also found at the homozygous state in a simplex subject in whom no residual glucocerebrosidase activity of GBA2 could be evidenced in blood cells, opening the way to a possible measurement of this enzyme activity in clinical practice. The overall phenotype was a complex HSP with mental impairment, cataract, and hypogonadism in males associated with various degrees of corpus callosum and cerebellar atrophy on brain imaging. Antisense morpholino oligonucleotides targeting the zebrafish GBA2 orthologous gene led to abnormal motor behavior and axonal shortening/branching of motoneurons that were rescued by the human wild-type mRNA but not by applying the same mRNA containing the missense mutation. This study highlights the role of ceramide metabolism in HSP pathology.
The sulfate radical pathway of the room-temperature degradation of two phenolic compounds in water is reported in this study. The sulfate radicals were produced by the cobalt-mediated decomposition ...of peroxymonosulfate (Oxone) in an aqueous homogeneous system. The major intermediates formed from the transformation of 2,4-dichlorophenol were 2,4,6-trichlorophenol, 2,3,5,6-tetrachloro-1,4-benzenediol, 1,1,3,3-tetrachloroacetone, pentachloroacetone, and carbon tetrachloride. Those resulting from the transformation of phenol in the presence of chloride ion were 2-chlorophenol, 4-chlorophenol, 2,4-dichlorophenol, 2,6-dichlorophenol, 1,1,3,3-tetrachloroacetone, and pentachloroacetone. In the absence of chloride ion, phenol transformed into 2,5-cyclohexadiene-1,4-dione (quinone), 1,2-benzenediol (catechol), and 1,4-benzenediol (hydroquinone). Several parameters were varied, and their impact on the transformation of the organic compounds is also discussed. The parameters varied were the initial concentration of the organic substrate, the dose of Oxone used, the cobalt counteranion, and in particular the impact of chloride ions and the quenching agent utilized for terminating the reaction. This is one of the very few studies dealing with intermediates formed via sulfate radical attack on phenolic compounds. It is also the first study that explores the sulfate radical mechanism of oxidation, when sulfate radicals are generated via the Co/Oxone reagent. Furthermore, it provides strong evidence on the interaction of chloride ions with sulfate radicals leading to halogenation of organics in water.
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