Seeing double with a multifunctional reservoir computer.

Multifunctional biological neural networks exploit multistability in order to perform multiple tasks without changing any network properties. Enabling artificial neural networks (ANNs) to obtain certain multistabilities in order to perform several tasks, where each task is related to a particular attractor in the network's state space, naturally has many benefits from a machine learning perspective. Given the association to multistability, in this paper, we explore how the relationship between different attractors influences the ability of a reservoir computer (RC), which is a dynamical system in the form of an ANN, to achieve multifunctionality. We construct the "seeing double" problem in order to systematically study how a RC reconstructs a coexistence of attractors when there is an overlap between them. As the amount of overlap increases, we discover that for multifunctionality to occur, there is a critical dependence on a suitable choice of the spectral radius for the RC's internal network connections. A bifurcation analysis reveals how multifunctionality emerges and is destroyed as the RC enters a chaotic regime that can lead to chaotic itinerancy.

Barriers to HIV care in Uganda and implications for universal test-and-treat: a qualitative study.

Achieving universal HIV test-and-treat will require targeted interventions for those with worse outcomes, including advanced HIV. We conducted qualitative, semi-structured interviews with healthcare workers (HCWs) and people living with HIV (PLWH) at 5 HIV clinics in Kampala, Uganda, to understand barriers to care. PLWH enrolled started/restarted on HIV treatment ≤3 months prior. PLWH were grouped as 1) "ART-experienced" or those restarted therapy after ≥12 months off, 2) ART naïve CD4 count <100 cells/uL "late presenters" or 3) ART naïve CD4 count >350 cells/uL "early presenters". In-depth interviews were conducted in Luganda, translated, and transcribed verbatim. Between May and August 2017, 58 PLWH and 20 HCWs were interviewed. High stigma and low social support emerged as themes among all as barriers to care. Alcohol abuse was a barrier for men. Fear of domestic violence and abandonment were barriers for women, limiting disclosure of their HIV status to their male partners. Clinic factors such as rapport with staff, distance, efficiency, and privacy impacted care. Future interventions to decrease delayed ART initiation should target stigma and social support. Assisted disclosure, contact tracing, and alcohol abuse treatment should be implemented. Strengthening client support, reducing wait times, and increasing privacy assurances would improve care-seeking behaviors.

Quantifying the effect of shade on cuticle morphology and carbon isotopes of sycamores: present and past.

PREMISE: Reconstructing the light environment and architecture of the plant canopy from the fossil record requires the use of proxies, such as those derived from cell wall undulation, cell size, and carbon isotopes. All approaches assume that plant taxa will respond predictably to changes in light environments. However, most species-level studies looking at cell wall undulation only consider "sun" or "shade" leaves; therefore, we need a fully quantitative taxon-specific method. METHODS: We quantified the response of cell wall undulation, cell size, and carbon isotopes of Platanus occidentalis using two experimental setups: (1) two growth chambers at low and high light and (2) a series of outdoor growth experiments using green and black shade cloth at different densities. We then developed and applied a proxy for daily light integral (DLI) to fossil Platanites leaves from two early Paleocene floras from the San Juan Basin in New Mexico. RESULTS: All traits responded to light environment. Cell wall undulation was the most useful trait for reconstructing DLI in the geological record. Median reconstructed DLI from early Paleocene leaves was ~44 mol m-2 d-1 , with values from 28 to 54 mol m-2 d-1 . CONCLUSIONS: Cell wall undulation of P. occidentalis is a robust, quantifiable measurement of light environment that can be used to reconstruct the paleo-light environment from fossil leaves. The distribution of high DLI values from fossil leaves may provide information on canopy architecture; indicating that either (1) most of the canopy mass is within the upper portion of the crown or (2) leaves exposed to more sunlight are preferentially preserved.

Multifunctionality in a reservoir computer.

Multifunctionality is a well observed phenomenological feature of biological neural networks and considered to be of fundamental importance to the survival of certain species over time. These multifunctional neural networks are capable of performing more than one task without changing any network connections. In this paper, we investigate how this neurological idiosyncrasy can be achieved in an artificial setting with a modern machine learning paradigm known as "reservoir computing." A training technique is designed to enable a reservoir computer to perform tasks of a multifunctional nature. We explore the critical effects that changes in certain parameters can have on the reservoir computers' ability to express multifunctionality. We also expose the existence of several "untrained attractors"; attractors that dwell within the prediction state space of the reservoir computer were not part of the training. We conduct a bifurcation analysis of these untrained attractors and discuss the implications of our results.

Symmetry kills the square in a multifunctional reservoir computer.

The learning capabilities of a reservoir computer (RC) can be stifled due to symmetry in its design. Including quadratic terms in the training of a RC produces a "square readout matrix" that breaks the symmetry to quell the influence of "mirror-attractors," which are inverted copies of the RC's solutions in state space. In this paper, we prove analytically that certain symmetries in the training data forbid the square readout matrix to exist. These analytical results are explored numerically from the perspective of "multifunctionality," by training the RC to specifically reconstruct a coexistence of the Lorenz attractor and its mirror-attractor. We demonstrate that the square readout matrix emerges when the position of one attractor is slightly altered, even if there are overlapping regions between the attractors or if there is a second pair of attractors. We also find that at large spectral radius values of the RC's internal connections, the square readout matrix reappears prior to the RC crossing the edge of chaos.

Clinical Characteristics of Active Tuberculosis Diagnosed After Starting Treatment for Latent Tuberculosis Infection.

Although rare, subclinical tuberculosis disease can be missed during evaluations for latent tuberculosis infection, and can manifest with symptoms during latent tuberculosis treatment. Among over 8000 patients treated for latent tuberculosis we found no evidence of acquired drug resistance, underscoring the safety of rifampin monotherapy for latent tuberculosis.

Structure-function relationships in histidine-rich antimicrobial peptides from Atlantic cod.

Gad-1 and Gad-2 are antimicrobial peptide (AMP) sequences encoded by paralogous genes. They are rich in histidine, which suggests that their activity might be pH-dependent. We examined their structure-function relationships with a view to learning how to improve AMP therapeutic ratios. Activity assays with Gram-negative bacteria and cancer cell lines demonstrate that Gad-2 is substantially more active at slightly acidic pH than it is at neutral pH. By contrast, the activity of Gad-1 at lower pH is similar to its activity at pH7. Circular dichroism spectra indicate that the greater functional plasticity of Gad-2 correlates with a greater structural plasticity; Gad-2's percent helicity varies dramatically with altered pH and lipid environment. Interestingly, Gad-2's highest levels of helicity do not correspond to the conditions where it is most active. High resolution solution NMR structures were determined in SDS micelles at pH5, conditions that induce an intermediate level of helicity in the peptides. Gad-1 is more helical than Gad-2, with both peptides exhibiting the greatest helical tendencies in their central region and lowest helicity in their N-termini. The high resolution structures suggest that maximum activity relies on the appropriate balance between an N-terminal region with mixed hydrophobic/hydrophilic structure features and an amphipathic central and C-terminal region. Taken together with previous studies, our results suggest that to improve the therapeutic ratio of AMPs, consideration should be given to including sequential histidine-pairs, keeping the overall charge of the peptide modest, and retaining a degree of structural plasticity and imperfect amphipathicity.

Exploring the origins of switching dynamics in a multifunctional reservoir computer.

The concept of multifunctionality has enabled reservoir computers (RCs), a type of dynamical system that is typically realized as an artificial neural network, to reconstruct multiple attractors simultaneously using the same set of trained weights. However, there are many additional phenomena that arise when training a RC to reconstruct more than one attractor. Previous studies have found that in certain cases, if the RC fails to reconstruct a coexistence of attractors, then it exhibits a form of metastability, whereby, without any external input, the state of the RC switches between different modes of behavior that resemble the properties of the attractors it failed to reconstruct. In this paper, we explore the origins of these switching dynamics in a paradigmatic setting via the "seeing double" problem.

Sarcopenia Is an Independent Risk Factor for Proximal Junctional Disease Following Adult Spinal Deformity Surgery.

STUDY DESIGN: Retrospective cohort study. OBJECTIVES: Sarcopenia is a risk factor for medical complications following spine surgery. However, the role of sarcopenia as a risk factor for proximal junctional disease (PJD) remains undefined. This study evaluates whether sarcopenia is an independent predictor of proximal junctional kyphosis (PJK) and proximal junctional failure (PJF) following adult spinal deformity (ASD) surgery. METHODS: ASD patients who underwent thoracic spine to pelvis fusion with 2-year clinical and radiographic follow-up were reviewed for development of PJK and PJD. Average psoas cross-sectional area on preoperative axial computed tomography or magnetic resonance imaging at L4 was recorded. Previously described PJD risk factors were assessed for each patient, and multivariate linear regression was performed to identify independent risk factors for PJK and PJF. Disease-specific thresholds were calculated for sarcopenia based on psoas cross-sectional area. RESULTS: Of 32 patients, PJK and PJF occurred in 20 (62.5%) and 12 (37.5%), respectively. Multivariate analysis demonstrated psoas cross-sectional area to be the most powerful independent predictor of PJK (P = .02) and PJF (P = .009). Setting ASD disease-specific psoas cross-sectional area thresholds of <12 cm2 in men and <8 cm2 in women resulted in a PJF rate of 69.2% for patients below these thresholds, relative to 15.8% for those above the thresholds. CONCLUSIONS: Sarcopenia is an independent, modifiable predictor of PJK and PJF, and is easily assessed on standard preoperative computed tomography or magnetic resonance imaging. Surgeons should include sarcopenia in preoperative risk assessment and consider added measures to avoid PJF in sarcopenic patients.

Apoptosis-inducing factor contributes to epithelial cell apoptosis induced by enteropathogenic Escherichia coli.

The mechanisms by which enteropathogenic Escherichia coli (EPEC) causes intestinal epithelial cell apoptosis remain unclear. We tested the hypothesis that apoptosis-inducing factor (AIF) is involved in apoptosis induced by EPEC. Infection of intestinal epithelial cells in vitro with EPEC led to the mitochondrial and cytosolic accumulation of AIF. This effect was partially dependent on caspase activity. Knockdown of AIF with siRNA blocked cellular apoptosis in response to EPEC infection, as assessed by poly(ADP-ribose) polymerase cleavage and oligonucleosome formation. Taken together, these data suggest that caspase-dependent mobilization of AIF contributes to EPEC-induced epithelial cell apoptosis.

Povidone-iodine irrigation combined with Vancomycin powder lowers infection rates in pediatric deformity surgery.

BACKGROUND: Surgical site infection is a morbid, devastating complication after spinal procedures. Studies have investigated the effect of wound lavage with 3.5% Povidone-iodine solution or the use of intrawound Vancomycin powder. We examined the effect of Povidone-iodine irrigation, intrawound Vancomycin powder, or a combination of both agents in a tertiary care Pediatric Hospital. METHODS: We queried our health system database for patients undergoing spinal surgery over an eight-year span between January 2008 and June 2016 and identified patient cohorts who received no intervention, intrawound Vancomycin alone, Povidone-iodine irrigation alone, or a combination of both agents. Infection rates were determined. The effect of treatment on outcome was analyzed using a logistic regression model. RESULTS: 475 patients were identified who met study inclusion criteria. 88 non-neuromuscular patients received no intra-operative agent. The surgical site infection (SSI) rate in this group of patients was 10%. For the 194 non-neuromuscular scoliosis patients who received Povidone-iodine and Vancomycin powder, the infection rate was reduced to 0.7%. The SSI rate in the 180 non-neuromuscular patients who were treated with Vancomycin powder alone was 1.4%. 13 patients were treated with Povidone-iodine lavage only, with a small sample size precluding statistical comparison. Infection rate in the 132 neuromuscular disease patients decreased from 14 to 7% overall during this time span: while the odds ratio of infection was reduced in all neuromuscular treatment groups receiving intra-operative measures, statistical significance was not reached in any neuromuscular group studied. CONCLUSIONS: A protocol using combined 3.5% weight/volume Povidone-iodine and Vancomycin powder was associated with the lowest infection rate in our non-neuromuscular patient population and should be considered as a low cost intervention in pediatric patients undergoing spinal deformity procedures. LEVEL OF EVIDENCE: Level II.

Relationship between socioeconomic status and risk of sexually transmitted infections in Uganda: Multilevel analysis of a nationally representative survey.

Socioeconomic status (SES) appears to have positive and negative associations with sexually transmitted infection (STI) risk in resource-limited settings, but few studies have evaluated nationally representative data. We assessed multiple SES measures and their effect on STI risk. We conducted a secondary analysis of data from the Uganda Demographic and Health Survey (UDHS 2011). The primary outcome (STI risk) was self-reported STIs and/or symptoms in the prior 12 months. We examined associations between multiple SES measures and STI risk using a mixed-effects Poisson regression model. The results showed that of the 9256 sexually active individuals, 7428 women and 1828 men were included in the analysis. At an individual level, middle wealth quintile and disposable income were associated with STI risk, whereas being in the richest wealth quintile was protective. Residence in wealthier regions (adjusted incidence rate ratio [aIRR] 3.92, 3.62, and 2.75, for Central, Western, and Eastern regions; p < 0.01) was associated with increased STI risk. Regional level analysis revealed stochastic variability of STI risk across geographical region (variance 0.03; p = 0.01). The bilateral association between SES and STI risk underscores the need for multi-sectoral interventions to address the upstream effects of poverty on STI risk and downstream effects of STIs on health and economic productivity.

Seizures in Human Immunodeficiency Virus-Associated Cryptococcal Meningitis: Predictors and Outcomes.

BACKGROUND: Seizures commonly occur in patients with cryptococcal meningitis, yet risk factors and outcomes related to seizures are not well described. METHODS: We performed post hoc analyses on participants prospectively enrolled in 3 separate human immunodeficiency virus (HIV)-associated cryptococcal meningitis clinical trials during 2010-2017. Documentation of seizures at presentation or during hospitalization and antiseizure medication receipt identified participants with seizures. We summarized participant characteristics by seizure status via Kruskal-Wallis and χ 2 tests. Cox proportional hazards models analyzed the relationship between seizures and mortality. We compared mean quantitative neurocognitive performance Z (QNPZ-8) scores, and individual domain z-scores, at 3-months using independent t tests. RESULTS: Among 821 HIV-infected cryptococcal meningitis participants, 28% (231 of 821) experienced seizures: 15.5% (127 of 821) experienced seizures at presentation, and 12.7% (104 of 821) experienced incident seizures. Participants with seizures at presentation had a significantly lower Glasgow coma scale ([GCS] <15; P < .001), CD4 count (<50 cells/mcL; P = .02), and higher cerebrospinal fluid (CSF) opening pressure (>25 cm H2O; P = .004) when compared with participants who never experienced seizures. Cerebrospinal fluid fungal burden was higher among those with seizures at presentation (125 000 Cryptococcus colony-forming units [CFU]/mL CSF) and with seizures during follow-up (92 000 CFU/mL) compared with those who never experienced seizures (36 000 CFU/mL, P < .001). Seizures were associated with increased 10-week mortality (adjusted hazard ratio = 1.45; 95% confidence interval, 1.11-1.89). Participants with seizures had lower neurocognitive function at 3 months (QNPZ-8 = -1.87) compared with those without seizures (QNPZ-8 = -1.36; P < .001). CONCLUSIONS: Seizures were common in this HIV-associated cryptococcal meningitis cohort and were associated with decreased survival and neurocognitive function.

Utilization of Osseous Landmarks for Anatomic Anterior Cruciate Ligament Femoral Tunnel Placement.

Accurate placement of the femoral tunnel is critical for long-term clinical success following anterior cruciate ligament (ACL) reconstruction. The purpose of the present study is to evaluate the accuracy of femoral tunnel placement when referencing osseous landmarks during ACL reconstruction. We hypothesize that referencing osseous landmarks during ACL reconstruction consistently results in anatomic placement of the ACL femoral tunnel. This study was a retrospective case series. We reviewed 83 consecutive ACL reconstructions performed by a single surgeon. The lateral intercondylar ridge and lateral bifurcate ridge were referenced intraoperatively for anatomic placement of the ACL femoral tunnel during single-bundle reconstruction. Using these landmarks, the femoral tunnel was placed in the center of the anteromedial bundle footprint on the lateral wall of the intercondylar notch. We reviewed all operative notes and intraoperative arthroscopic images to assess tunnel placement. Postoperative anteroposterior and lateral radiographs were obtained in all patients. Anatomic placement was confirmed by review of lateral radiographs utilizing both the quadrant method (QM) and Blumensaat-ridge ratio (BRR). We used a total of 80 patients for our study. Review of arthroscopic images confirmed anatomic placement of the ACL femoral tunnel in all patients. All patients demonstrated that the femoral tunnel was placed anatomically according to the BRR method. Using the QM, all femoral tunnels were placed anatomically except for one tunnel that was placed slightly anteriorly. There was excellent agreement between the two radiographic measurement techniques. The principal finding of this study indicates that the lateral intercondylar ridge and the lateral bifurcate ridge are reliable landmarks for anatomic placement of the ACL femoral tunnel. Referencing osseous landmarks during surgery can help surgeons avoid nonanatomic placement of the ACL femoral tunnel, especially in cases where the soft-tissue footprint is no longer present. Furthermore, both the radiographic QM and the BRR are valid techniques to assess for anatomic ACL femoral tunnel placement both intraoperatively and postoperatively.

Socioeconomic position and ten-year survival and virologic outcomes in a Ugandan HIV cohort receiving antiretroviral therapy.

Lifelong ART is essential to reducing HIV mortality and ending the epidemic, however the interplay between socioeconomic position and long-term outcomes of HIV-infected persons receiving antiretroviral therapy (ART) in sub-Saharan Africa is unknown. Furthering the understanding of factors related to long-term ART outcomes in this important region will aid the successful scale-up of ART programs. We enrolled 559 HIV-infected Ugandan adults starting ART in 2004-2005 at the Infectious Diseases Institute in Kampala, Uganda and followed them for 10 years. We documented baseline employment status, regular household income, education level, housing description, physical ability, and CD4 count. Viral load was measured every six months. Proportional hazard regression tested for associations between baseline characteristics and 1) mortality, 2) virologic failure, and 3) mortality or virologic failure as a composite outcome. Over ten years 23% (n = 127) of participants died, 6% (n = 31) were lost-to-follow-up and 23% (107/472) experienced virologic treatment failure. In Kaplan-Meier analysis we observed an association between employment and mortality, with the highest cumulative probability of death occurring in unemployed individuals. In univariate analysis unemployment and disease severity were associated with mortality, but in multivariable analysis the only association with mortality was disease severity. We observed an association between higher household income and an increased incidence of both virologic failure and the combined outcome, and an association between self-employment and lower incidence of virologic failure and the combined outcome when compared to unemployment. Formal education level and housing status were unrelated to outcomes. It is feasible to achieve good ten-year survival, retention-in-care, and viral suppression in a socioeconomically diverse population in a resource-limited setting. Unemployment appears to be related to adverse 10-year ART outcomes. A low level of formal education does not appear to be a barrier to successful long-term ART.

Evolving Failures in the Delivery of Human Immunodeficiency Virus Care: Lessons From a Ugandan Meningitis Cohort 2006-2016.

BACKGROUND: Because of investments in human immunodeficiency virus (HIV) care in sub-Saharan Africa, the number of people aware of their status and receiving antiretroviral therapy (ART) has increased; however, HIV/acquired immune deficiency syndrome (AIDS) mortality still remains high. METHODS: We performed retrospective analysis of 3 sequential prospective cohorts of HIV-infected Ugandan adults presenting with AIDS and meningitis from 2006 to 2009, 2010 to 2012, and 2013 to 2016. Participants were categorized as follows: (1) unknown HIV status; (2) known HIV+ without ART; (3) known HIV+ with previous ART. We further categorized 2006 and 2013 cohort participants by duration of HIV-status knowledge and of ART receipt. RESULTS: We screened 1353 persons with suspected meningitis. Cryptococcus was the most common pathogen (63%). Over the decade, we observed an absolute increase of 37% in HIV status knowledge and 59% in antecedent ART receipt at screening. The 2006 cohort participants were new/recent HIV diagnoses (65%) or known HIV+ but not receiving ART (35%). Many 2013 cohort participants were new/recent HIV diagnoses (34%) and known HIV+ with <1 month ART (20%), but a significant proportion were receiving ART 1-4 months (11%) and >4 months (30%). Four percent of participants discontinued ART. From 2010 to 2016, meningitis cases per month increased by 33%. CONCLUSIONS: Although improved HIV screening and ART access remain much-needed interventions in resource-limited settings, greater investment in viral suppression and opportunistic infection care among the growing HIV-infected population receiving ART is essential to reducing ongoing AIDS mortality.

SGLT-1-mediated glucose uptake protects intestinal epithelial cells against LPS-induced apoptosis and barrier defects: a novel cellular rescue mechanism?

Excessive apoptosis induced by enteric microbes leads to epithelial barrier defects. This mechanism has been implicated in the pathogenesis of inflammatory bowel diseases (IBD) and bacterial enteritis. The sodium-dependent glucose cotransporter (SGLT-1) is responsible for active glucose uptake in enterocytes. The aim was to investigate the effects of SGLT-1 glucose uptake on enterocyte apoptosis and barrier defects induced by bacterial lipopolysaccharide (LPS). SGLT-1-transfected Caco-2 cells were treated with LPS (50 mug/mL) in low (5 mM) or high (25 mM) glucose media. LPS in low glucose induced caspase-3 cleavage, DNA fragmentation, and increased paracellular permeability to dextran in epithelial cells. These phenomena were significantly attenuated in high glucose. LPS increased SGLT-1 activity in high, but not low glucose media. Addition of phloridzin, which competitively binds to SGLT-1, inhibited the cytoprotection mediated by high glucose. Western blot showed that LPS in high glucose increased the levels of anti-apoptotic Bcl-2 and Bcl-X(L,) and did not change proapoptotic Bax. Differential extraction of membranous vs. cytosolic cell components demonstrated that high glucose inhibits mitochondrial cytochrome c translocation to cytosol. Collectively, SGLT-1-mediated glucose uptake increases anti-apoptotic proteins, and protects enterocytes from LPS-induced apoptosis and barrier defects. The understanding of this novel glucose-mediated rescue mechanism may lead to therapeutic interventions for various enteric diseases.

Consequences of elevated temperature and pCO2 on insect folivory at the ecosystem level: perspectives from the fossil record.

Paleoecological studies document the net effects of atmospheric and climate change in a natural laboratory over timescales not accessible to laboratory or ecological studies. Insect feeding damage is visible on well-preserved fossil leaves, and changes in leaf damage through time can be compared to environmental changes. We measured percent leaf area damaged on four fossil leaf assemblages from the Bighorn Basin, Wyoming, that range in age from 56.1 to 52.65 million years (Ma). We also include similar published data from three US sites 49.4 to ~45 Ma in our analyses. Regional climate was subtropical or warmer throughout this period, and the second oldest assemblage (56 Ma) was deposited during the Paleocene-Eocene Thermal Maximum (PETM), a geologically abrupt global warming event caused by massive release of carbon into the atmosphere. Total and leaf-chewing damage are highest during the PETM, whether considering percent area damaged on the bulk flora, the average of individual host plants, or a single plant host that occurs at multiple sites. Another fossil assemblage in our study, the 52.65 Ma Fifteenmile Creek paleoflora, also lived during a period of globally high temperature and pCO 2, but does not have elevated herbivory. Comparison of these two sites, as well as regression analyses conducted on the entire dataset, demonstrates that, over long timescales, temperature and pCO 2 are uncorrelated with total insect consumption at the ecosystem level. Rather, the most important factor affecting herbivory is the relative abundance of plants with nitrogen-fixing symbionts. Legumes dominate the PETM site; their prevalence would have decreased nitrogen limitation across the ecosystem, buffering generalist herbivore populations against decreased leaf nutritional quality that commonly occurs at high pCO 2. We hypothesize that nitrogen concentration regulates the opposing effects of elevated temperature and CO 2 on insect abundance and thereby total insect consumption, which has important implications for agricultural practices in today's world of steadily increasing pCO 2.

Host epithelial interactions with Helicobacter pylori: a role for disrupted gastric barrier function in the clinical outcome of infection?

Infection of the human stomach with Helicobacter pylori may develop into gastritis, ulceration, adenocarcinoma and mucosal lymphomas. The pathogenic mechanisms that determine the clinical outcome from this microbial-epithelial interaction remain poorly understood. An increasing number of reports suggests that disruptions of epithelial barrier function may contribute to pathology and postinfectious complications in a variety of gastrointestinal infections. The aim of this review is to critically discuss the implications of H pylori persistence on gastric disease, with emphasis on the role of myosin light chain kinase, claudins and matrix metalloproteinases in gastric permeability defects, and their contribution to the development of cancer. These mechanisms and the associated signalling events may represent novel therapeutic targets to control disease processes induced by H pylori, a microbial pathogen that colonizes the stomach of over 50% of the human population.