Objective This guideline provides evidence-based recommendations on treating patients who present with dysphonia, which is characterized by altered vocal quality, pitch, loudness, or vocal effort ...that impairs communication and/or quality of life. Dysphonia affects nearly one-third of the population at some point in its life. This guideline applies to all age groups evaluated in a setting where dysphonia would be identified or managed. It is intended for all clinicians who are likely to diagnose and treat patients with dysphonia. Purpose The primary purpose of this guideline is to improve the quality of care for patients with dysphonia, based on current best evidence. Expert consensus to fill evidence gaps, when used, is explicitly stated and supported with a detailed evidence profile for transparency. Specific objectives of the guideline are to reduce inappropriate variations in care, produce optimal health outcomes, and minimize harm. For this guideline update, the American Academy of Otolaryngology-Head and Neck Surgery Foundation selected a panel representing the fields of advanced practice nursing, bronchoesophagology, consumer advocacy, family medicine, geriatric medicine, internal medicine, laryngology, neurology, otolaryngology-head and neck surgery, pediatrics, professional voice, pulmonology, and speech-language pathology. Action Statements The guideline update group made strong recommendations for the following key action statements (KASs): (1) Clinicians should assess the patient with dysphonia by history and physical examination to identify factors where expedited laryngeal evaluation is indicated. These include, but are not limited to, recent surgical procedures involving the head, neck, or chest; recent endotracheal intubation; presence of concomitant neck mass; respiratory distress or stridor; history of tobacco abuse; and whether the patient is a professional voice user. (2) Clinicians should advocate voice therapy for patients with dysphonia from a cause amenable to voice therapy. The guideline update group made recommendations for the following KASs: (1) Clinicians should identify dysphonia in a patient with altered voice quality, pitch, loudness, or vocal effort that impairs communication or reduces quality of life (QOL). (2) Clinicians should assess the patient with dysphonia by history and physical examination for underlying causes of dysphonia and factors that modify management. (3) Clinicians should perform laryngoscopy, or refer to a clinician who can perform laryngoscopy, when dysphonia fails to resolve or improve within 4 weeks or irrespective of duration if a serious underlying cause is suspected. (4) Clinicians should perform diagnostic laryngoscopy, or refer to a clinician who can perform diagnostic laryngoscopy, before prescribing voice therapy and document/communicate the results to the speech-language pathologist (SLP). (5) Clinicians should advocate for surgery as a therapeutic option for patients with dysphonia with conditions amenable to surgical intervention, such as suspected malignancy, symptomatic benign vocal fold lesions that do not respond to conservative management, or glottic insufficiency. (6) Clinicians should offer, or refer to a clinician who can offer, botulinum toxin injections for the treatment of dysphonia caused by spasmodic dysphonia and other types of laryngeal dystonia. (7) Clinicians should inform patients with dysphonia about control/preventive measures. (8) Clinicians should document resolution, improvement or worsened symptoms of dysphonia, or change in QOL of patients with dysphonia after treatment or observation. The guideline update group made a strong recommendation against 1 action: (1) Clinicians should not routinely prescribe antibiotics to treat dysphonia. The guideline update group made recommendations against other actions: (1) Clinicians should not obtain computed tomography (CT) or magnetic resonance imaging (MRI) for patients with a primary voice complaint prior to visualization of the larynx. (2) Clinicians should not prescribe antireflux medications to treat isolated dysphonia, based on symptoms alone attributed to suspected gastroesophageal reflux disease (GERD) or laryngopharyngeal reflux (LPR), without visualization of the larynx. (3) Clinicians should not routinely prescribe corticosteroids for patients with dysphonia prior to visualization of the larynx. The policy level for the following recommendation about laryngoscopy at any time was an option: (1) Clinicians may perform diagnostic laryngoscopy at any time in a patient with dysphonia. Disclaimer This clinical practice guideline is not intended as an exhaustive source of guidance for managing dysphonia (hoarseness). Rather, it is designed to assist clinicians by providing an evidence-based framework for decision-making strategies. The guideline is not intended to replace clinical judgment or establish a protocol for all individuals with this condition, and it may not provide the only appropriate approach to diagnosing and managing this problem. Differences from Prior Guideline (1) Incorporation of new evidence profiles to include the role of patient preferences, confidence in the evidence, differences of opinion, quality improvement opportunities, and any exclusion to which the action statement does not apply (2) Inclusion of 3 new guidelines, 16 new systematic reviews, and 4 new randomized controlled trials (3) Inclusion of a consumer advocate on the guideline update group (4) Changes to 9 KASs from the original guideline (5) New KAS 3 (escalation of care) and KAS 13 (outcomes) (6) Addition of an algorithm outlining KASs for patients with dysphonia.
Recent studies of several multi-body D0 meson decays have revealed that the final states are dominantly CP-even. However, the small value of the width difference between the two physical eigenstates ...of the D0–D‾0 system indicates that the total widths of decays to CP-even and CP-odd final states should be the same to within about a percent. The known contributions to the width difference from hadronic D0 decays are discussed, and it is shown that an apparent excess of quasi-CP-even modes is balanced, within current uncertainty, by interference effects in quasi-flavour-specific decays. Decay modes which may significantly affect the picture with improved measurements are considered.
Host inflammation alters the availability of nutrients such as iron to limit microbial growth. However, Salmonella enterica serovar Typhimurium thrives in the inflamed gut by scavenging for iron with ...siderophores. By administering Escherichia coli strain Nissle 1917, which assimilates iron by similar mechanisms, we show that this nonpathogenic bacterium can outcompete and reduce S. Typhimurium colonization in mouse models of acute colitis and chronic persistent infection. This probiotic activity depends on E. coli Nissle iron acquisition, given that mutants deficient in iron uptake colonize the intestine but do not reduce S. Typhimurium colonization. Additionally, the ability of E. coli Nissle to overcome iron restriction by the host protein lipocalin 2, which counteracts some siderophores, is essential, given that S. Typhimurium is unaffected by E. coli Nissle in lipocalin 2-deficient mice. Thus, iron availability impacts S. Typhimurium growth, and E. coli Nissle reduces S. Typhimurium intestinal colonization by competing for this limiting nutrient.
Display omitted
•Probiotic E. coli Nissle reduces Salmonella intestinal colonization and persistence•E. coli Nissle outcompetes Salmonella for iron in the inflamed gut•Specialized iron transporters are essential for E. coli Nissle probiotic activity•E. coli Nissle overcomes lipocalin 2-mediated iron sequestration
We present a measurement of R_{K^{*}}, the branching fraction ratio B(B→K^{*}μ^{+}μ^{-})/B(B→K^{*}e^{+}e^{-}), for both charged and neutral B mesons. The ratio for the charged case R_{K^{*+}} is the ...first measurement ever performed. In addition, we report absolute branching fractions for the individual modes in bins of the squared dilepton invariant mass q^{2}. The analysis is based on a data sample of 711 fb^{-1}, containing 772×10^{6} BBover ¯ events, recorded at the ϒ(4S) resonance with the Belle detector at the KEKB asymmetric-energy e^{+}e^{-} collider. The obtained results are consistent with standard model expectations.
Exposure of lysine-containing peptide-based gelators to the cross-linking agent glutaraldehyde allows tuning of gel mechanical properties. The effect of cross-linking depends on the position of the ...lysine residue in the peptide chain, the concentration of gelator and the conditions under which cross-linking takes place. Through control of these factors, cross-linking leads to increased gel strength.
Cross-linking lysine-containing peptide-based gelators with glutaraldehyde allows tuning of the final gel mechanical properties.
The experimental results on the ratios of branching fractions R(D)=B(Bover ¯→Dτ^{-}νover ¯_{τ})/B(Bover ¯→Dℓ^{-}νover ¯_{ℓ}) and R(D^{*})=B(Bover ¯→D^{*}τ^{-}νover ¯_{τ})/B(Bover ¯→D^{*}ℓ^{-}νover ...¯_{ℓ}), where ℓ denotes an electron or a muon, show a long-standing discrepancy with the standard model predictions, and might hint at a violation of lepton flavor universality. We report a new simultaneous measurement of R(D) and R(D^{*}), based on a data sample containing 772×10^{6} BBover ¯ events recorded at the ϒ(4S) resonance with the Belle detector at the KEKB e^{+}e^{-} collider. In this analysis the tag-side B meson is reconstructed in a semileptonic decay mode and the signal-side τ is reconstructed in a purely leptonic decay. The measured values are R(D)=0.307±0.037±0.016 and R(D^{*})=0.283±0.018±0.014, where the first uncertainties are statistical and the second are systematic. These results are in agreement with the standard model predictions within 0.2, 1.1, and 0.8 standard deviations for R(D), R(D^{*}), and their combination, respectively. This work constitutes the most precise measurements of R(D) and R(D^{*}) performed to date as well as the first result for R(D) based on a semileptonic tagging method.
There is clear research evidence that physical work environments (i.e., material spaces and objects) influence employee performance and wellbeing. As a result, these environments have received ...significant attention from both practitioners and researchers. However, the outcomes of these applied initiatives and research studies are difficult to compare because they often lack a common framework or are focused exclusively on the objective qualities of the workspace (e.g., lighting, acoustics) without considering the human element. In this article, we outline a series of studies conducted to examine employees’ psychological reactions to the physical work environment. A three-part framework for these reactions is proposed, and a supporting measure is developed and validated. This new measure, the Reactions to the Physical Work Environment Scale (RPWES), assesses key cognitive, emotional, and relational responses of employees to their physical work environment. The RPWES provides the foundation for a broader understanding of the impact of the physical work environment on employees. Implications for theory and practice are discussed.
•Focus, sense of beauty and connectedness key features of physical work environment.•New framework measures cognitive, emotional and relational reactions to key features.•Reactions related to important organizational outcomes, e.g. collaboration.•Important to develop physical work environments catering to individual differences.
Most supramolecular gels are stable or assumed to be stable over time, and aging effects are often not studied. However, some gels do show clear changes on aging, and a small number of systems ...exhibit gel-to-crystal transitions. In these cases, crystals form over time, typically at the expense of the network underpinning the gel; this leads to the gel falling apart. These systems are rare, and little is known about how these gel-to-crystal transitions occur. Here, we use a range of techniques to understand in detail a gel-to-crystal transition for a specific functionalised dipeptide based gelator. We show that the gel-to-crystal transition depends on the final pH of the medium which we control by varying the amount of glucon-δ-lactone (GdL) added. In the gel phase, at low concentrations of GdL, and at early time points with high concentrations of GdL, we are able to show the nanometre scale dimensions of the self-assembled fibre using SAXS; however there is no evidence of molecular ordering of the gel fibres in the WAXS. At low concentrations of GdL, these self-assembled fibres stiffen with time but do not crystallise over the timescale of the SAXS experiment. At high concentrations of GdL, the fibres are already stiffened, and then, as the pH drops further, give way to the presence of crystals which appear to grow preferentially along the direction of the fibre axis. We definitively show therefore that the gel and crystal phase are not the same. Our work shows that many assumptions in the literature are incorrect. Finally, we also show that the sample holder geometry is an important parameter for these experiments, with the rate of crystallisation depending on the holder in which the experiment is carried out.
Most supramolecular gels are stable or assumed to be stable over time, and aging effects are often not studied.
Multicomponent supramolecular systems can be used to achieve different properties and new behaviors compared to their corresponding single component systems. Here, a two‐component system is used, ...showing that a non‐gelling component modifies the assembly of the gelling component, allowing access to co‐assembled structures that cannot be formed from the gelling component alone. The systems are characterized across multiple length scales, from the molecular level by NMR and CD spectroscopy to the microstructure level by SANS and finally to the material level using nanoindentation and rheology. By exploiting the enhanced mechanical properties achieved through addition of the second component, multicomponent noodles are formed with superior mechanical properties to those formed by the single‐component system. Furthermore, the non‐gelling component can be triggered to crystallize within the multicomponent noodles, allowing the preparation of new types of hierarchical composite noodles.
Multicomponent assembly of 2NapFF with the structurally similar functionalized dipeptide 2NapLG causes changes to the formed first‐order supramolecular structures. These changes to assembly allow access to new properties and behaviors. This multicomponent system can be used to form mechanically robust supramolecular noodles. Through a change in external conditions (a reduction in pH), crystals can be formed within these noodles.
Binding of transcription factor (TF) proteins to regulatory DNA sites is key to accurate control of gene expression in response to environmental stimuli. Theoretical modeling of transcription ...regulation is often focused on a limited set of genes of interest, while binding of the TF to other genomic sites is seldom considered. The total number of TF binding sites (TFBSs) affects the availability of TF protein molecules and sequestration of a TF by TFBSs can promote bistability. For many signaling systems where a graded response is desirable for continuous control over the input range, biochemical parameters of the regulatory proteins need be tuned to avoid bistability. Here we analyze the mono-/bistable parameter range for positively autoregulated two-component systems (TCSs) in the presence of different numbers of competing TFBSs. TCS signaling, one of the major bacterial signaling strategies, couples signal perception with output responses via protein phosphorylation. For bistability, competition for TF proteins by TFBSs lowers the requirement for high fold change of the autoregulated transcription but demands high phosphorylation activities of TCS proteins. We show that bistability can be avoided with a low phosphorylation capacity of TCSs, a high TF affinity for the autoregulated promoter or a low fold change in signaling protein levels upon induction. These may represent general design rules for TCSs to ensure uniform graded responses. Examining the mono-/bistability parameter range allows qualitative prediction of steady-state responses, which are experimentally validated in the E. coli CusRS system.
PDF
