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The European Union Biodiversity Strategy 2030 (EUBDS) aims to regain biodiversity through enhanced forest conservation and protection, which may lead to increased timber harvest in non-EU countries. We aimed to identify the potential leakage of biodiversity risks as induced by the EUBDS. We created an indicator framework that allows one to quantify vulnerability of forest biodiversity. The framework is based on 26 biodiversity indicators for which indicator values were publicly available. We weighted single indicator values with countrywise modeled data on changed timber production under EUBDS implementation. Nearly 80% of the indicators pointed to higher vulnerability in the affected non-EU countries. Roundwood production was transferred to countries with, on average, lower governance quality (p = 0.0001), political awareness (p = 0.548), forest coverage (p = 0.034), and biomass (p = 0.272) and with less sustainable forest management (p = 0.044 and p = 0.028). These countries had more natural habitats (p = 0.039) and intact forest landscapes (p = 0.0001) but higher risk of species extinction (p = 0.006) and less protected area (p = 0.0001) than the EU countries. Only a few indicators pointed to lower vulnerability and biodiversity risks outside the EU. Safeguards are needed to ensure that implementation of EUBDS does not cause harm to ecosystems elsewhere. The EU regulation on deforestation-free supply chains might have limited effects because the sustainable management of existing and even expanding forests is not well considered. Sustained roundwood production in the EU is needed to avoid placing more pressure on more vulnerable ecosystems elsewhere. Decreasing species and habitat indicator values nevertheless call for global conservation and protection schemes. The EUBDS helped pave the way to the Kunming-Montreal Biodiversity Framework. Yet, lower values for the indicators mean governance and biodiversity engagement in non-EU countries suggest that this global framework might not sufficiently prevent leakage of risks to biodiversity. Effective land-use planning is necessary to balance conservation schemes with roundwood production., (© 2024 The Authors. Conservation Biology published by Wiley Periodicals LLC on behalf of Society for Conservation Biology.)

Objective: To examine the efficacy and safety of two doses of long-acting acetaminophen in patients with osteoarthritis (OA) of the hip or knee., Methods: This multicenter, randomized, double-blind, parallel-group, placebo-controlled study evaluated the efficacy and safety of acetaminophen extended-release (ER) 650 mg and 1300 mg given three times daily for the treatment of moderate to moderately severe OA of the hip or knee. Primary efficacy end points were mean change from baseline through 12 weeks in the Western Ontario and McMaster Universities Osteoarthritis Index pain and physical function subscale scores and mean patient global assessment of response to therapy at week 12. Safety assessments included monitoring vital signs, adverse events, study joint assessments, and clinical laboratory results at each study visit., Results: Four hundred eighty-three patients were randomized to treatment and included in the intent-to-treat analysis. All groups were similar with respect to baseline demographics except for gender, weight, and body mass index. Acetaminophen ER 3900 mg was significantly superior to placebo for all three primary end points; acetaminophen ER 1950 mg was significantly superior to placebo only with respect to patient assessment of response to therapy. Study treatments were generally well tolerated, and there was no significant difference among the groups in the overall number of adverse events., Conclusions: Acetaminophen ER 3900 mg/d administered for up to 12 weeks was effective in treating moderate to moderately severe chronic OA pain of the hip or knee and was generally well tolerated.

Background: New antiviral drugs are available for the treatment of influenza type A and type B infections. In clinical practice, antiviral use has rarely been guided by antecedent laboratory diagnosis. Defined clinical predictors of an influenza infection can help guide timely therapy and avoid unnecessary antibiotic use., Objective: To examine which clinical signs and symptoms are most predictive of influenza infection in patients with influenza-like illness using a large data set derived from clinical trials of zanamivir., Methods: This analysis is a retrospective, pooled analysis of baseline signs and symptoms from phase 2 and 3 clinical trial participants. It was conducted in mainly unvaccinated (mean age, 35 years) adults and adolescents who had influenza-like illness, defined as having fever or feverishness plus at least 2 of the following influenza-like symptoms: headache, myalgia, cough, or sore throat who underwent laboratory testing for influenza. Clinical signs and symptoms were evaluated in statistical models to identify those best predicting laboratory confirmation of influenza., Results: Of 3744 subjects enrolled with baseline influenza-like symptoms, and included in this analysis, 2470 (66%) were confirmed to have influenza. Individuals with influenza were more likely to have cough (93% vs 80%), fever (68% vs 40%), cough and fever together (64% vs 33%), and/or nasal congestion (91% vs 81%) than those without influenza. The best multivariate predictors of influenza infections were cough and fever with a positive predictive value of 79% (P<. 001). The positive predictive value rose with the increase in the temperature at the time of recruitment., Conclusion: When influenza is circulating within the community, patients with an influenza-like illness who have both cough and fever within 48 hours of symptom onset are likely to have influenza and the administration of influenza antiviral therapy may be appropriate to consider. Arch Intern Med. 2000;160:3243-3247.

Objective: The purpose of this study was to assess the costs and treatments associated with influenza patients with and without secondary viral or bacterial infections in a managed care setting., Methods: Patients with influenza diagnoses (ICD-9 = 487) were identified in the PharMetrics database between January 1, 1997 and June 30, 1998. Patients were placed into 3 cohorts: influenza only (INF), influenza plus a secondary bacterial respiratory infection (BRI), and influenza plus a secondary viral respiratory infection (VRI). The index date was defined as the date of the first occurrence of an influenza diagnosis during the study period. Medical claims were assessed from the index date to the end of the influenza episode, which was defined as the date of the last claim for influenza followed by a 90-day "clean period" during which no influenza-related charges occurred., Results: A total of 18,000 patients met the inclusion criteria. The mean age was 29 years, and 54% were female. Approximately 93% of patients were placed in the INF cohort, and 3% each in the BRI and VRI groups. The BRI cohort had the highest mean total cost ($5593* SD = 10,939), compared with the VRI cohort ($847 SD = 1782) and INF cohort ($602 SD = 2813) (P less than.0001 vs INF; P less than.0001 vs VRI). This total cost disparity was primarily driven by differences in inpatient costs: BRI ($3509, SD = 9474); VRI ($208, SD = 1327); INF ($138, SD = 2145). Patients in the BRI cohort averaged 0.5 hospitalizations per patient vs 0.06 in the VRI cohort and 0.03 in the INF cohort., Conclusions: Subjects in the BRI cohort were significantly more costly and had an increased risk of hospitalization as compared with subjects in the VRI or INF cohorts. Early intervention with antiviral agents and/or antibiotics, where appropriate, could result in significant cost savings for managed care organizations.

Human serum (MBP) and human recombinant (rMBP) mannose-binding protein bind to mannose-rich, serum-resistant Salmonella montevideo (SH5770), enhance C3 deposition, and render the organisms serum-sensitive. We investigated structural features of MBP necessary for this effect. MBP has a cysteine-rich amino-terminal region, a collagen-like region, and a carboxyl-terminal carbohydrate-recognition domain. We prepared carbohydrate-recognition domains lacking the other two domains either by deletion mutagenesis (delta MBP, 16 kDa) or by collagenase digestion of whole rMBP (cdMBP, 16-18 kDa). Whole and truncated MBP were detected on immunoblot by specific monoclonal antibodies that recognize both bound and free MBP. rMBP enhanced C3 deposition on SH5770 8-fold, while cdMBP and delta MBP did not increase C3 deposition over control levels. All forms of MBP bound to SH5770 by enzyme-linked immunosorbent assay and by measuring binding of radiolabeled whole and truncated MBP. Binding by 125I-delta MBP was inhibited by mannan and by MBP. Thus failure of truncated MBPs to enhance C3 deposition was not due to failure to specifically bind carbohydrate residues. To determine the molecular form of truncated MBP in nondenaturing conditions, 125I-delta MBP was centrifuged through a 5-20% sucrose-density gradient. The peak of 125I-delta MBP sedimented to estimated S20,w 2.01, but larger multimers also were present. Multimers bound SH5770 with higher affinity than monomers. We conclude that carbohydrate-recognition regions of MBP produced by collagenase digestion or by deletion mutagenesis are sufficient for ligand binding. However, the collagen-like region is necessary for MBP enhancement of C3 deposition on SH5770.

Mannose-binding protein was purified from human serum to apparent homogeneity by affinity chromatography on mannose-Sepharose, followed by affinity chromatography on underivatized Sepharose. Approximately 0.4 mg protein was obtained from 1 liter serum. The glycosphingolipid-binding specificity of the purified protein was examined by chromatogram overlay and solid phase assays. It binds with high affinity to Lc-3Cer (GlcNAc beta 1-3Gal beta 1-4Glc beta 1-1ceramide) and n-Lc5Cer (GlcNAc beta 1-3Gal beta 1-4GlcNAc beta 1-3Gal beta 1-4Glc beta 1-1ceramide). It does not bind to many other glycosphingolipids without terminal N-acetylglucosamine residues that were tested. Thus, these data suggest that N-acetylglucosamine-terminated glycosphingolipids may serve as cell-surface attachment sites for mannose-binding protein in vivo. In addition, the binding specificity of the protein can be used as a sensitive probe for determining the levels of Lc3Cer and nLc5Cer in tissues, as it exhibits half-maximal binding to about 10 pmol of these lipids in solid phase assays, and detects less than 20 pmol of Lc3Cer in chromatogram overlay assays. This technique was utilized to demonstrate that one sample of chronic myeloid leukemia cells contains both Lc3Cer and nLc5Cer.

To better define relationships among pneumococcal anticapsular antibodies, opsonophagocytosis, and in vivo mouse protection, we measured these functions in sera from healthy individuals who had not received pneumococcal vaccine. For serotype 1 pneumococci, the level of antibody measured by radioimmunoassay did not predict mouse protection, as has been noted by others. For some sera, opsonic requirements for antibody and complement could be clearly demonstrated and a strong correlation obtained between concentration of antibody and degree of phagocytic killing. However, for most sera, antibody concentration did not correlate with opsonic activity, as measured by phagocytic bactericidal assay or uptake of radiolabeled bacteria. Sera with high concentrations of anticapsular antibody did not always support in vitro bacterial killing by leukocytes. Conversely, highly opsonic sera did not necessarily have substantial levels of measurable antibody. Moreover, in vitro opsonophagocytic activity failed to predict in vivo protection; sera could be opsonic in vitro but not protective in vivo and vice versa. For serotype 3 pneumococci, antibody concentrations correlated strongly with mouse protective titers, as has been noted by others for type 3. Opsonophagocytosis, as measured by leukocyte bactericidal activity, required both complement and heat-stable substance(s) present in high-antibody sera, presumably antibody. Furthermore, increasing concentrations of serum enhanced phagocytic killing in a fashion that could be correlated with anticapsular antibody content. However, correlation with opsonophagocytosis was not so strong as with mouse protection, and there was no correlation between antibody concentration and opsonization as measured by uptake of radiolabeled bacteria. These observations suggest that opsonophagocytosis (with the definitive end point of bacterial killing) cannot be the standard against which to measure antibody concentrations. Furthermore, host protective mechanisms against pneumococci remain to be clearly defined. Even if opsonization by anticapsular antibody is the primary mechanism, there is need for development of improved functional assays of protection.