Browse Articles

Discover research articles across all indexed journals

Improving restoration heuristics to support anadromous fish passage

PLoS ONE Sunny L. Jardine, Logan Blair, Catalina Burch et al. Jun 03, 2026 DOI: 10.1371/journal.pone.0348150

Investments in restoring river connectivity are growing worldwide to support freshwater biodiversity. Although optimization methods exist for selecting cost-effective restoration portfolios, decisions are often guided by simple heuristic rules. For example, managers may prioritize restoring barriers blocking the largest amounts of high-quality upstream habitat, ignoring the position of other barriers in the system. These heuristics often rely on proxies for watershed connectivity and habitat quality. Using anadromous fish passage restoration in western Washington, USA, as a case study, we show that redesigning these heuristics can yield substantial performance gains. Benchmarking common heuristics against optimization outcomes reveals that connectivity proxies based on total upstream habitat can achieve 93% of optimal gains when increasing habitat quantity is the sole objective, but adding widely used proxies for habitat quality (e.g., percent of upstream natural land cover) can cut performance nearly in half. These findings underscore the importance of designing heuristics that more directly target high-quality habitat gains to improve investment efficiency and help close the science–practice gap between optimization research and on-the-ground restoration decisions.

Dimerization-Dependent Trans-Domain Coupling Enables Intermediate Transfer in Fungal Haloacid Dehalogenase-Like Terpene Cyclases

Journal of the American Chemical Society Tzu-Ho Chen, Kai-Fa Huang, Ting-Hung Chou et al. Jun 03, 2026 DOI: 10.1021/jacs.6c04151

Detection of culprit presence in multiple-culprit crimes: A comparison of combined and separate lineup-presentation formats

PLoS ONE Ulla Lichtenhagen, Nicola Marie Menne, Raoul Bell et al. Jun 03, 2026 DOI: 10.1371/journal.pone.0336456

Although crimes involving multiple culprits are widespread, there is still a lack of understanding of how the police should construct lineups for multiple suspects in these cases. In most of the few guidelines that exist it is recommended to present multiple lineups separately in succession, with each lineup including one suspect. This replicates, for each suspect in a multiple-culprit case, the procedure used for a single suspect in a single-culprit case. However, this recommendation could be reconsidered if it turned out that, if multiple culprits are present in the lineups, the face of one culprit serves as a contextual facial cue that enhances the eyewitness’s ability to detect another culprit within the same display—an effect that could only occur if all lineups are presented together in a combined lineup-presentation format, allowing them to be visible concurrently. Two experiments using a staged-crime video with four culprits were conducted to test whether presenting simultaneous lineups combined as opposed to separately affects culprit-presence detection. In Experiment 1, it was tested whether culprit-presence detection differs between combined and separate lineup-presentation formats. No significant difference was found, indicating comparable performance between the two lineup-presentation formats. In Experiment 2, we compared a condition in which three culprit-present lineups were combined—allowing for multiple potential contextual facial cues—with conditions involving separate lineups and combined lineups with only one culprit-present lineup, where contextual facial cueing was theoretically not possible. Culprit-presence detection did not differ between the combined format with three culprit-present lineups and the other conditions. Given the absence of clear benefits of the combined-lineup-presentation format, a cautious, pragmatic conclusion is to continue presenting each suspect in a separate lineup, consistent with most current recommendations.

Predicting habitat suitability of Korean Lindera as Tertiary relict plants under climate change scenarios

PLoS ONE Jaewon Seol, Hye-jin Kwon, Songhie Jung et al. Jun 03, 2026 DOI: 10.1371/journal.pone.0350199

Climate change profoundly affects plant habitats and ecological niches, particularly among Tertiary relict flora—remnants of warm and humid climatic conditions that prevailed during the Tertiary period—which are recognized as highly climate-sensitive lineages. The genus Lindera (Lauraceae), a representative group of deciduous broad-leaved trees in East Asian temperate forests, provides an ideal model for examining shifts in habitat suitability and changes in predicted suitable environments under future climate change scenarios. In this study, we developed ensemble species distribution models (SDMs) using six algorithms to predict the distributions of four Lindera species— L. obtusiloba, L. glauca, L. erythrocarpa , and L. sericea —under three Shared Socioeconomic Pathway (SSP) scenarios (SSP1–2.6, SSP3–7.0, SSP5–8.5). Among the three categories of environmental variables, climatic factors exerted the greatest influence on habitat suitability, with temperature seasonality (bio4) and growing-season precipitation (gsp) identified as the primary determinants. With intensifying climate change, suitable habitats shifted northward and upward, accompanied by pronounced habitat losses across southern and central Korea. Despite its broad geographic range, L. obtusiloba exhibited an 81% reduction in suitable habitat, whereas L. sericea , due to its localized distribution, showed a 91% decrease and was identified as the most climate-vulnerable species. Ecological niche overlap (Schoener’s D ) declined across all scenarios, indicating increasing ecological differentiation among species. Although the four Lindera species exhibited distinct spatial responses, all consistently experienced range contractions and reduced overlap in predicted suitable environments, indicating high vulnerability to climate change. These results suggest that intrinsic ecological traits, climatic sensitivity, and niche stability—rather than current geographic range extent—are key determinants of species persistence. Accordingly, Lindera species in southern Korea should be considered climate-vulnerable taxa, and conservation strategies should integrate the protection of climatically stable refugia with complementary conservation measures beyond natural habitats to ensure long-term persistence under future climate change.

Cationic Diradicals Derived from Non-Aufbau Radicals toward Magnetoluminescence and Qubit Applications

Journal of the American Chemical Society Qi Sun, Jean-Luc Bredas, Veaceslav Coropceanu Jun 03, 2026 DOI: 10.1021/jacs.6c04678

The routine use of nasopharyngeal airway in the setting of monitored anesthesia care during gastrointestinal endoscopy: A multi-center single blinded randomized controlled trial

PLoS ONE Christian Raphael, Nancy Abou Nafeh, Marc Moukarzel et al. Jun 03, 2026 DOI: 10.1371/journal.pone.0349946

Background and Aims Monitored anesthesia care (MAC) is commonly used for gastrointestinal (GI) endoscopy, allowing patients to breathe spontaneously while sedated. Despite its benefits, MAC is associated with respiratory adverse events, such as desaturation or the need for interventions. Limited studies have examined the effectiveness of nasopharyngeal airways (NPA) in reducing airway maneuvers and improving respiratory stability during MAC. The study evaluates the efficacy and safety of NPA in reducing the occurrence of at least one airway intervention/desaturation in patients undergoing GI endoscopy under MAC. Methods This multi-center, single-blinded randomized controlled trial involved patients undergoing GI endoscopy under MAC. A total of 329 patients were randomly assigned to either the NPA or control group. Primary outcomes included a composite primary outcome: occurrence of at least one airway intervention/desaturation. Secondary outcomes included adverse events, satisfaction scores of patients and healthcare providers, and the joint effects of NPA use and OSA risk on the occurrence of at least one airway intervention or desaturation. Results The NPA group showed significantly lower incidence of occurrence of at least one airway intervention/desaturation compared to controls (18.5% vs. 40.1%, P  < 0.001). NPA significantly reduced the occurrence of at least one airway intervention/desaturation in both low and intermediate/high risk OSA groups. The reduction was stronger in low OSA risk group (OR=0.23, 95%CI [0.11–0.49]) versus intermediate/high OSA risk group (OR=0.45, 95%CI [0.21–0.95]. Health care provider satisfaction was significantly higher in the NPA group (p < 0.001). Mild, self-resolving epistaxis occurred in 3.1% of NPA patients. Conclusions NPA use reduces airway interventions and enhances satisfaction among anesthesiologists and gastroenterologists during GI endoscopy under MAC. Routine utilization of NPAs in this context may be considered.

Prevalence of multiple morbidities and cancers in individuals with Down syndrome: A matched descriptive study using linked electronic health record data

PLoS ONE Caoimhe McKenna, Kabir Yoshinori Khanna, Meghan A. Cupp et al. Jun 03, 2026 DOI: 10.1371/journal.pone.0349794

Background Down syndrome is associated with the development of multiple morbidities throughout the life course, yet comprehensive data on its relative burden remains limited. This descriptive, matched, retrospective cohort study aimed to assess the 20-year period prevalence of morbidities and cancers in adults and children with Down syndrome. Methods We analysed electronic health record data from January 1998 to December 2017, matching individuals with Down syndrome to up to five matched controls. Period prevalence and odds ratios (OR) were calculated for 30 morbidities and 24 cancers. Results This study included 4,648 individuals with Down syndrome (32,920 person-years) and 23,238 matched controls (236,883 person-years). Most morbidities had a significantly higher period prevalence in individuals with Down syndrome, including hypothyroidism (30.4%), congenital cardiac disease (27.8%), and epilepsy (21.9%). We found an increased comparative risk of autism (OR 7.5, 95% CI 6.4–8.0), chronic kidney disease (OR 2.4, 95% CI 2.1–2.8) and inflammatory bowel disease (OR 2.5, 95% CI 2.2–2.8). Individuals with Down syndrome also had a significantly higher period prevalence of leukaemia and testicular cancer. Conversely, most solid tumours were less prevalent in individuals with Down syndrome. Conclusions This study presents findings from one of the largest described cohorts of individuals with Down syndrome, contributing to an understanding of the comparative prevalence of multiple comorbidities and cancers among both adults and children with Down syndrome. These findings support prioritising surveillance for a range of conditions such as hypothyroidism and childhood leukaemia and may justify de-emphasising routine screening for several solid tumours in Down syndrome.

Neuroticism, extraversion, and emotion sensitivity in a nonclinical young adult sample

PLoS ONE Lauren A. Rutter, Prabhvir Lakhan, Laura Germine Jun 03, 2026 DOI: 10.1371/journal.pone.0349027

Introduction Accurate recognition of others’ emotional facial expressions, referred to as emotion sensitivity (ES), is a central component of nonverbal communication. Previous research suggests that personality traits such as neuroticism and extraversion may shape nonverbal emotion decoding but findings have been mixed. The present study examined whether these traits predict performance on the Belmont Emotion Sensitivity Test (BEST), a task designed to measure subtle discrimination of anger, fear, and happiness while minimizing response bias. Method A sample of 289 college students completed self-report measures of neuroticism and extraversion, as well as the Belmont Emotion Sensitivity Test (BEST), which assesses the ability to discriminate subtle differences in facial expressions of fear, anger, and happiness. Depression, anxiety, and stress levels were also measured. Results Female participants reported higher levels of neuroticism ( t  = 4.39, p  < .001; d  = .59) and extraversion ( t  = 2.33, p  = .02; d  = .33) t han male participants. Neuroticism severity was positively correlated with depression, anxiety, and stress. Extraversion was negatively correlated with depression, anxiety, and stress (range of r s = .55−.68, p  < .001). Multiple regressions showed that neither neuroticism nor extraversion significantly predicted ES scores for any emotion category. Discussion Although women reported higher levels of neuroticism and extraversion, these traits did not predict performance on a validated emotion sensitivity task. These findings suggest that, in this nonclinical young adult sample, neuroticism and extraversion were not robust predictors of performance on this measure of emotion sensitivity. Implications are discussed for theories linking personality, psychopathology, and nonverbal emotion perception.

Benzo-Fused Medium-Sized Heterocycles with a Chiral C–N Axis from Asymmetric Cycloaddition and Skeletal Rearrangement

Journal of the American Chemical Society Luo-Yu Wang, Jiaoting Pan, Mingjin Liu et al. Jun 03, 2026 DOI: 10.1021/jacs.6c06686

Salivary osmolality measured by MX3 hydration testing system demonstrates high reliability but limited validity in elite athlete hydration assessment

PLoS ONE Stefan Pettersson, Lykke Tamm, Stig Mattsson et al. Jun 03, 2026 DOI: 10.1371/journal.pone.0349955

Accurate assessment of hydration is essential for both athletic performance and health, yet remains challenging outside controlled settings. This study evaluated the validity and reliability of salivary osmolality (SOSM), measured using a handheld osmometer (MX3 Hydration Testing System), as a marker of morning hydration status in elite athletes. A total of 230 paired fasted-morning saliva and urine sample sets from 118 Olympic-level athletes (57% female; age 27 ± 5 years; BMI 24 ± 2) were included in the analyses. Urine specific gravity (USG) served as the reference. Validity was examined using ICC(3,1), ROC analysis, and Cohen’s κ, and test–retest reliability was assessed from three repeated SOSM readings from the same saliva sample. SOSM showed no meaningful correspondence with USG (ICC = 0.00; 95% CI [−0.13, 0.13]) and no meaningful classification agreement (κ = −0.02; 95% CI [−0.15, 0.10]). Diagnostic accuracy was poor across all examined threshold comparisons, with AUCs of 0.40–0.49, indicating chance-level to worse-than-chance discrimination, sensitivity 40–69%, and specificity 23–65%. By contrast, within-sample repeated SOSM measurements were highly consistent (ICC = 0.93; 95% CI [0.91, 0.94]), with a standard error of measurement of 7.9 mOsm and a minimal detectable change (MDC 90 ) of 18.4 mOsm. These findings indicate that the MX3 device is repeatable when reading the same saliva sample, but SOSM lacks validity as a stand-alone marker of first-morning hydration status in elite athletes under free-living conditions.

Ligand-Orchestrated Burst Nucleation Enables Ultrasmall Phase-Pure High-Entropy Nanoalloys with Active-Armor Interfaces

Journal of the American Chemical Society Rui Ma, Chongyuan Zhai, Ru-Yu Zhou et al. Jun 03, 2026 DOI: 10.1021/jacs.6c05904

Staphylococcus aureus agr-type vs genetic background: molecular signatures determining differential metabolism and virulence potential

PLoS ONE Mariane Pivard, Julian Bär, Tomas Demeter et al. Jun 03, 2026 DOI: 10.1371/journal.pone.0350108

In Staphylococcus aureus , the quorum‑sensing accessory gene regulator ( agr ) system is the major virulence regulator. The four agr ‑types (I-IV) have been associated with distinct infection outcomes, but their direct contribution to virulence regulation and metabolism has remained unresolved due to tight linkage between agr ‑type and genetic background. To disentangle agr ‑type‑specific effects, we used congenic Newman strains in which the native agr -locus has been replaced with each of the four agr -types, alongside a Δ agr mutant. We performed RNA‑sequencing during early exponential (1h30), late exponential (6h), and stationary (12h) growth phases. Despite similar growth kinetics, agr ‑types displayed distinct activation profiles based on agrA and RNAIII expressions. Agr -I and agr -IV showed early, strong expressions, agr -II displayed intermediate expressions and agr -III initiated weak expressions only in stationary phase. This agr ‑type‑dependent activation timing was the dominant driver of global transcriptional changes. Early activation in agr ‑I and agr ‑IV induced robust expression of phenol‑soluble modulins, capsule biosynthesis genes, and pore‑forming toxins, whereas agr ‑II and agr ‑III expressed delayed or alternative virulence pathways, including upregulation of superantigen‑like genes. Among all types, agr ‑IV exhibited the broadest transcriptional response, encompassing both virulence and metabolic pathways, including differential regulation of nucleotide and fructose metabolisms. Pairwise differential expression, over‑representation analysis, and gene‑set enrichment consistently revealed agr ‑type‑specific virulence and metabolic programs. Agr ‑III, which activated latest and weakest, showed limited transcriptional change until stationary phase, whereas agr ‑I, agr ‑II, and agr ‑IV displayed progressively broader virulence and metabolic remodeling. Together, these findings demonstrate that agr ‑type determines virulence and metabolic gene expression profiles primarily by dictating the timing and magnitude of agr -activation, even within an identical genetic background and growth environment. This work provides a systematic framework for understanding agr ‑type‑specific regulatory strategies and their potential roles in S. aureus pathogenesis.

Light-Programmable Morphology in Photothermal Polyurethanes Based on Stenhouse Salt as Photothermal Agent

Journal of the American Chemical Society Livius F. Muff, Melissa H. M. M. Hanegraaf, Yuncong Hu et al. Jun 03, 2026 DOI: 10.1021/jacs.6c04477

Analysis of rational use and misuse of antibiotics in emergency departments: A cross-sectional study

PLoS ONE Huseyin Gurbuz, Selda Aslan, Muhammet Emin Doğan et al. Jun 03, 2026 DOI: 10.1371/journal.pone.0350138

Objective To assess antibiotic prescribing frequency and the appropriateness of prescriptions based on established rational antibiotic use principles among adult patients evaluated in the emergency department. Methods This retrospective, cross-sectional study was conducted in the emergency department of a tertiary university hospital between 1 January and 30 June 2022. Adult patients (≥18 years) who received or were prescribed antibiotics were included. Demographic, clinical, and microbiological data were retrieved from the hospital information management system. Prescriptions were evaluated against rational antibiotic use criteria defined by the World Health Organization (WHO) and the Turkish Medicines and Medical Devices Agency (TİTCK). Results A total of 595 patients were analyzed (62.4% female; mean age, 31.1 ± 14.2 years). Antibiotics were prescribed in 95.8% of encounters. Amoxicillin–clavulanic acid was the most commonly used agent (58.7%), followed by amoxicillin (8.7%) and metronidazole (5.6%). Microbiological culture sampling was conducted in only 0.8% of cases. Among patients who received antibiotic therapy (n = 570), 87.2% of prescriptions were classified as appropriate and 12.8% were classified as inappropriate according to guideline-based evaluation. In the overall cohort, 4.2% of patients did not receive antibiotic therapy. Most treated patients received a single antibiotic (95.8%), whereas dual antibiotic therapy was infrequently used (4.0%). Conclusion Antibiotic prescribing in the emergency department was notably high, accompanied by critically low rates of microbiological investigation. The findings demonstrate a persistent reliance on empirical therapy. Enhancing diagnostic support, promoting culture-guided treatment, and incorporating routine antimicrobial de-escalation strategies may help strengthen rational antibiotic use and warrant further evaluation.

State-Specific Nonresonant and Resonant Plasmon-Driven Electron Transfer into Single Molecules

Journal of the American Chemical Society Zhiwei Liu, Jiayu Xu, Xiang Zhu et al. Jun 03, 2026 DOI: 10.1021/jacs.5c21031

Integrating satellite data and field surveys to predict bird communities in the Peruvian Amazon

PLoS ONE Andrew Christopher Slater, Chris A. Kirkby, Chris Ketola et al. Jun 03, 2026 DOI: 10.1371/journal.pone.0329343

Tropical forests harbour some of the highest biodiversity on Earth but are undergoing rapid loss and degradation. In the Amazon more than one-third of forests have been altered through human activities, with major implications for wildlife communities. While Earth observation satellites effectively monitor forest cover at scale, it remains unclear how well satellite-derived variables capture variation in bird communities. We tested whether Landsat reflectance and vegetation indices can predict bird species occurrence and community composition in the Peruvian Amazon. We analysed 3,129 point counts and mist-net bird surveys conducted over 16 years in the Tambopata Forest, south-eastern Peru. As predictors we compared the effectiveness of remote sensing derived surface reflectance and vegetation indices (e.g., NDVI and tasselled cap), with traditional land-type and forest cover descriptors. Species occurrence probabilities and community composition of 135 frequently recorded bird species were estimated using multi-species occupancy models that account for imperfect detection. Models using Landsat reflectance and vegetation indices outperformed those based on habitat categories in predicting species occupancy (mean AUC = 0.68 vs 0.58). They also achieved high predictive accuracy (AUC > 0.7) for more species (49 compared with 20). However, low detection rates across surveys limited all models’ ability to accurately estimate full community composition and to detect change over time. Our results demonstrate that satellite-derived variables can improve predictions of bird occurrence compared with habitat categories, but their effectiveness depends strongly on survey design and species detectability. Integrating remote sensing with well-structured field surveys provides a scalable approach to monitoring biodiversity trends in tropical forests.

Modular Assembly of Higher-Order DNA Nanotube Tile Nanostructures Using DNA Annular Scaffolds

Journal of the American Chemical Society Sheng Zhi, Junke Wang, Shaokang Ren et al. Jun 03, 2026 DOI: 10.1021/jacs.6c04434

Infertility treatment and the growth of children from birth to 12 years of age: A national cohort study

PLoS ONE Yu-Shan Chang, Tsung Yu, Tzu-Jung Wong et al. Jun 03, 2026 DOI: 10.1371/journal.pone.0348091

Background Children conceived through infertility treatments may have altered birth outcomes and growth patterns compared to those conceived naturally. However, evidence on long-term growth trajectories, particularly distinguishing singletons and multiples, remains inconsistent. This study aimed to compare childhood growth trajectories from birth to 12 years of age between children conceived via infertility treatments and those conceived naturally, using a large national birth cohort. Methods We analyzed the follow-up data (6 months to 12 years of age) from the Taiwan Birth Cohort Study, an ongoing, nationwide, longitudinal study of children. Our final sample included 20,507 singletons (20,306 naturally conceived [NC], 104 via intrauterine insemination [IUI], 97 via in vitro fertilization [IVF]) and 950 multiples (670 NC, 68 IUI, 212 IVF). We used linear mixed models with random coefficient cubic splines for age to assess the growth trajectories for weight, height, and body mass index (BMI) by infertility treatment status and logistic regression to analyze risk of rapid weight gain, overweight, obesity, and underweight. Results Children conceived via IUI or IVF showed lower weight, height, and BMI in pooled analyses; however, these differences were largely attributable to the higher proportion of multiple births in the infertility treatment groups. After stratification by plurality, most differences were attenuated and not statistically significant, with the exception of slightly lower weight (−0.353 kg; p = 0.039) among IUI-conceived multiples. The risk of rapid weight gain (6 months–2 years) and underweight, overweight, or obesity (5.5–12 years) did not differ significantly by the conception mode after plurality was controlled. Conclusions After accounting for plurality, children conceived through infertility treatments showed similar growth trajectories to those conceived naturally. These findings are reassuring for families using infertility treatments and highlight the importance of minimizing multiple births in assisted reproduction to support optimal child growth and health outcomes.

Task demands and visual context naturalness modulate gravitational expectation during ocular tracking of temporarily occluded ballistic trajectories

PLoS ONE Sergio Delle Monache, Pietro Nastasi, Gianluca Paolocci et al. Jun 03, 2026 DOI: 10.1371/journal.pone.0328432

When intercepting a moving object, ocular and hand movements are often associated. The neural control of both tasks is known to combine sensory information with predictive mechanisms. When interacting with free-falling targets, the brain may integrate visual signals with an internal representation of gravity, which can be recruited also in virtual settings, when contextual cues about the environment naturalness are available. This internal representation may be shared between oculomotor and manual control. At the same time, concurrent execution of hand and eye movements may alter the oculomotor performance. Here, we investigated how task demands and visual context naturalness affected the relative weighting of sensory feedback and predictive information for ocular tracking control. Participants tracked targets, either congruent with gravity or perturbed with altered gravity, which were projected on either pictorial or neutral background. To enforce prediction, targets were occluded for variable intervals. One group of participants performed only ocular tracking, while another group also intercepted the targets. In general, subjects’ ocular tracking depended on the target acceleration and the visual context. The effects of gravitational expectations were more evident for the time dependent oculomotor indexes (smooth pursuit and saccadic τ) and with the pictorial background, reinforcing the idea that recruitment of the gravity prior depends on the visual context. Instead, for post saccadic error and smooth pursuit gain no clear dissociation emerged between the effects of acceleration and velocity. Finally, participants who only tracked the target showed strong reliance on gravitational expectation early on, by displaying systematic oculomotor changes with the target acceleration since its perturbation. Instead, participants that also intercepted the target relied less on the gravity prior until the target occlusion, after which they showed oculomotor performance compatible with gravitational expectation. Thus, concurrence of ocular tracking and manual interception strongly influenced the temporal recruitment of the gravity prior.

Characterizing the in vitro and in vivo effect of bicarbonate on azithromycin activity against Acinetobacter baumannii

PLoS ONE Hadley Jaramillo, Matthew Slarve, Derek Long et al. Jun 03, 2026 DOI: 10.1371/journal.pone.0350230

Carbapenem-resistant Acinetobacter baumannii (CRAB), a Gram-negative bacterial pathogen, has been identified by Centers for Disease Control (CDC) as the top priority pathogen for which new antibiotics are needed. We found that the addition of bicarbonate at physiologically normal levels found in the blood (23.8 mM) increased susceptibility of A. baumannii clinical isolates (n = 63) to azithromycin and resulted in MIC50 shift from 64 mg/L in CAMHB to 1–2 mg/L in CAMHB + bicarbonate (23.8 mM) or RPMI-1640 respectively. To characterize in vivo efficacy in murine blood and lung infection models, mice were infected with A. baumannii and then mice were treated with a human equivalent dosing strategy of azithromycin. In vivo outcomes greatly depended on the infection model used. The bloodstream infection model showed a statistically significant increase in survival of the treatment group compared to the control group. However, that was not found with the oral aspiration infection model. We hypothesize that these in vivo results are due to the local differences of bicarbonate concentrations at the site of infection throughout the course of infection.