You are well aware of the fact that ideas, thoughts, and resolutions, have the tendency to materialize. Some people speak of thought forms that will eventually become reality.
If you use the first training formula, i.e., 'my right arm is very heavy, certain changes will take place in that arm that last as long as you are in the Autogenic state. The formulas that follow induce other changes.
At the same time you can stretch and bend your arms vigorously, then breathe deeply and open your eyes. Canceling will not work as well if you open your eyes before you relax your arm muscles again. If you open your eyes prior to canceling, some feeling of heaviness or some other sensation may persist in your arms for some time. If you do not cancel correctly some heaviness may last for several hours, in rare cases even days.
The more determinedly and conscientiously you cancel, the more effective the whole practice of Autogenic Training will be. Should you fall asleep while practicing, you need not cancel, of course. The same holds if you are suddenly interrupted during your practice, by the telephone or the doorbell, for example. In such a case you will suffer a brief shock that makes it unnecessary to cancel.
All practice of Autogenic Training is simple. You sit or lie comfortably, preferably in a relaxed state. The Chi Generator® points at you from the side, about the middle of your body or, better, you carry a transfer disk of a Power Booster on you. A good setting for the Chi Generator® is 7.83Hz.
My left arm is very heavy.
Keep repeating this formula mentally. When you are repeating the formula in your mind, you should do so as intensely as you can. You may imagine it written before you or you may hear someone speak the formula, or both. You may even imagine yourself writing the formula onto a poster board.
It is important that you concentrate on the training formula. Your imagination helps this concentration. Should sudden ideas, thoughts, memories and the like appear, it is important that you do not attach yourself to them and that you pay them very little or no attention. Simply disregard them and keep focusing on the training formula that you keep repeating. Concentration will come with practice.
Should any unpleasant feeling occur during the practice, you should stop it with the proper canceling technique.
Repeat the heaviness practice five to six times when you practice for the first time. You may also practice until you actually feel the heaviness.
Usually the feeling of heaviness will come with the first practice. In some cases several practice sessions are necessary to induce this feeling.
Do not continue unless you have mastered the heaviness practice.
The induction of a feeling of warmth is aimed at relaxing the blood vessels. You should practice it after you have attained the feeling of heaviness. If you could not attain the feeling of heaviness after two weeks of practice, you can also proceed with the warmth formula.
A feeling of warmth indicates that the blood vessels have relaxed and dilated. The warmth practice will have results that are superior to the results of the progressive relaxation technique. Progressive relaxation techniques are very much the practice of choice in guided meditation practices as well as in some methods to induce hypnosis. States of relaxation that you can achieve with Autogenic Training are considerably deeper and much more thorough than what you can achieve with progressive relaxation and related methods. The warmth practice of Autogenic Training will prove this point to you beyond the shadow of any doubt. Especially the practices that follow will show you the tremendous control and power that you can achieve with the practice of Autogenic Training.
My right arm is very warm (six times) . . . . . . . .
Arms firm - Breathe deeply - Open eyes.
The feeling of heaviness indicates that the muscles are relaxed. If your practice regularly, the feeling of heaviness will appear rather quickly and noticeably, as soon as you think of heaviness.
The sensation of warmth is caused by the relaxation (dilation) of the blood vessel walls. It has been demonstrated that the feelings of warmth and heaviness are accompanied by actual physical changes. In other words, we are not dealing here with either a figment of the imagination of with a self deception. In fact, the arms will actually be slightly heavier as a result of increased blood supply into the relaxed, therefore, wider, blood vessels of the arms. For the same reason the temperature of the arms increases slightly. Special thermometers have shown that the increase in the arm's temperature can be more than 3.6 degrees F, and even more, in the hand, especially when the initial temperature was on the low side. Later you can learn powerful techniques to supply an increased amount of blood to any part of the body.
The autonomic nervous system is such that the state of tension in one group of muscles communicates itself automatically to the adjacent group. The tension spreads and increases as a consequence. On the other hand, when the muscles of the arm are relaxed, this relaxation too influences other groups of muscles until relaxation spreads ultimately over the whole body. This desired extension of heaviness and warmth (relaxation of muscles and blood vessels) over the whole body is called "generalization."
The more advanced the practitioner of Autogenic Training is the more heaviness and warmth appear as simple reflexes. At a later point of your training the feelings of warmth and heaviness may appear upon your intention to practice, even before you lie down and before you begin with the training.
With advancement you can also insert resolution formulae into your training while you are practicing.
The two basic exercises of heaviness and warmth result in a definite shifting of your body experience. Calmness is induced, the blood pressure may be normalized, pains reduced, spasms of asthma alleviated, indigestion, constipation, etc., can be dealt with, chronic spasms may begin to dissolve. According to Dr. Schultz, improvement and even cure of some dysfunctions followed the practice of Autogenic Training. The experience of warmth influences the entire circulatory system, because the relaxation of the blood vessels tends to spread from the left arm to the coronary vessels. Consequently more blood and oxygen go through the heart and heart pains often disappear.
It is possible to exchange practices three, i.e., the heart practice, and four, the breathing practice that you will find in the next section.
My heart beats calmly and regularly.
It is dangerous to use the formula 'my heart beats very calmly and slowly.' The heart reacts very strongly to that and serious disturbances may result.
When practicing the heart formula, you will likely discover your heart, i.e., you will learn to feel your heart.
The abdominal muscles react very sensitively to the psyche to an extent that in moments of extreme fear some people can actually soil themselves. Consequently, people who are very tense suffer from constipation, indigestion, and similar disturbances. Even the digestive glands are sensitive to our emotional conditions. Often they fail so that we cannot digest our food. Then they simply demand that we relax first and then eat.
The person who has frequent mood changes, whether he or she is aware of them or not, or who assumes faulty emotional postures, can easily make his or her body a whipping boy. This leads to a determined attempt to gain control of the autonomous nervous system with the help of Autogenic Training.
The solar plexus is part of the autonomous nervous system. It is the largest nervous network. It is located behind the stomach, in back of and to both sides of the mid spine. Being midway between the breastbone and the navel, the solar plexus regulates the function of the abdominal organs and transfers our moods to them.
Subjectively you will feel a pleasant warmth in the upper abdomen while you practice Autogenic training. Sometimes the entire body becomes warm. Occasionally you may first experience the feeling of warmth in the kidney area.
Formulaized resolutions, ten to thirty times repeated.
Calm - Heavy - Warm - Heart and breathing completely calm - Abdomen flowingly warm - Forehead pleasantly cool.
It is also very useful to keep records of your experiences in Autogenic Training. This is especially important if you combine your practice of Autogenic Training with a program of intuitive development, self help, and practices of neuro-cosmic programming.
If you are working toward self help and effective life force techniques, you will custom tailor your formulaized resolutions to your training.
Formulaized resolutions are also very helpful in dissolving the chronic spasms of your emotional armor. I suggest that you read the works of Wilhelm Reich.
The effects of Autogenic Training are enhanced significantly if you point a chi generator® towards yourself during practice, still more if you help it with an orgone radionics device or the manifestation program together with a Chi generator®.


text:
Guillain-Barré Syndrome Outbreak in Peru 2019 Associated With Campylobacter jejuni Infection
View ORCID ProfileAna P. Ramos, Sonja E. Leonhard, Susan K. Halstead, Mireya A. Cuba, Carlos C. Castañeda, View ORCID ProfileJose A. Dioses, Martin A. Tipismana, View ORCID ProfileJesus T. Abanto, Alejandro Llanos, Dawn Gourlay, Max Grogl, Mariana Ramos, View ORCID ProfileJesus D. Rojas, Rina Meza, Daniela Puiu, View ORCID ProfileRachel M. Sherman, View ORCID ProfileSteven L. Salzberg, View ORCID ProfilePatricia J. Simner, Hugh J. Willison, Bart C. Jacobs, David R. Cornblath, Hugo F. Umeres, Carlos A. Pardo
First published February 5, 2021, DOI: https://doi.org/10.1212/NXI.0000000000000952
Ana P. Ramos
From the Departamento de Medicina (A.P.R., M.A.C., C.C.C., J.A.D., M.A.T., J.T.A., H.F.U.), Servicio de Neurología y Neuropsiquiatría, Hospital Cayetano Heredia, Lima, Perú; Department of Neurology (S.E.L.) and Department of Neurology and Department of Immunology (B.C.J.), Erasmus MC, University Medical Center Rotterdam, Netherlands; Institute of Infection, Immunity and Inflammation (S.K.H., D.G., H.J.W.), University of Glasgow, United Kingdom; Departamento de Enfermedades Infecciosas Tropicales y Dermatológicas (A.L.), Hospital Cayetano Heredia, Lima, Perú; U.S. Naval Medical Research Unit-6 (M.G., M.R., J.D.R., R.M.), Lima, Peru; Center for Computational Biology (D.P., R.M.S., S.L.S.), Department of Computer Science, Whiting School of Engineering, Johns Hopkins University, Baltimore, MD; and Department of Pathology (P.J.S.), Department of Neurology (D.R.C.), and Department of Neurology and Department of Pathology (C.A.P.), Johns Hopkins University School of Medicine, Baltimore, MD.
ORCID record for Ana P. Ramos
Sonja E. Leonhard
For correspondence: s.leonhard@erasmusmc.nl
Susan K. Halstead
For correspondence: susan.halstead@glasgow.ac.uk
Mireya A. Cuba
For correspondence: mireya.cuba@upch.pe
Carlos C. Castañeda
For correspondence: ccastanedab@yahoo.com
Jose A. Dioses
ORCID record for Jose A. Dioses
For correspondence: jose.dioses.f@upch.pe
Martin A. Tipismana
For correspondence: martin.tipismana.b@upch.pe
Jesus T. Abanto
ORCID record for Jesus T. Abanto
For correspondence: jesus.abanto@upch.pe
Alejandro Llanos
For correspondence: alejandro.llanos.c@upch.pe
Dawn Gourlay
For correspondence: dawn.gourlay@glasgow.ac.uk
Max Grogl
For correspondence: max.grogl@gmail.com
Mariana Ramos
For correspondence: mariana.i.ramos.ln@mail.mil
Jesus D. Rojas
ORCID record for Jesus D. Rojas
For correspondence: jesus.d.rojas.ctr@mail.mil
Rina Meza
For correspondence: rina.a.meza2.ln@mail.mil
Daniela Puiu
For correspondence: dpuiu@jhu.edu
Rachel M. Sherman
ORCID record for Rachel M. Sherman
Steven L. Salzberg
ORCID record for Steven L. Salzberg
For correspondence: salzberg@jhu.edu
Patricia J. Simner
ORCID record for Patricia J. Simner
For correspondence: psimner1@jhmi.edu
Hugh J. Willison
For correspondence: hugh.willison@glasgow.ac.uk
Bart C. Jacobs
For correspondence: b.jacobs@erasmusmc.nl
David R. Cornblath
For correspondence: dcornbl@jhmi.edu
Hugo F. Umeres
For correspondence: hugo.umeres@upch.pe
Carlos A. Pardo
For correspondence: cpardov1@jhmi.edu
Ana P. Ramos, Sonja E. Leonhard, Susan K. Halstead, Mireya A. Cuba, Carlos C. Castañeda, Jose A. Dioses, Martin A. Tipismana, Jesus T. Abanto, Alejandro Llanos, Dawn Gourlay, Max Grogl, Mariana Ramos, Jesus D. Rojas, Rina Meza, Daniela Puiu, Rachel M. Sherman, Steven L. Salzberg, Patricia J. Simner, Hugh J. Willison, Bart C. Jacobs, David R. Cornblath, Hugo F. Umeres, Carlos A. Pardo
Objective To identify the clinical phenotypes and infectious triggers in the 2019 Peruvian Guillain-Barré syndrome (GBS) outbreak.
Methods We prospectively collected clinical and neurophysiologic data of patients with GBS admitted to a tertiary hospital in Lima, Peru, between May and August 2019. Molecular, immunologic, and microbiological methods were used to identify causative infectious agents. Sera from 41 controls were compared with cases for antibodies to Campylobacter jejuni and gangliosides. Genomic analysis was performed on 4 C jejuni isolates.
Results The 49 included patients had a median age of 44 years (interquartile range [IQR] 30–54 years), and 28 (57%) were male. Thirty-two (65%) had symptoms of a preceding infection: 24 (49%) diarrhea and 13 (27%) upper respiratory tract infection. The median time between infectious to neurologic symptoms was 3 days (IQR 2–9 days). Eighty percent had a pure motor form of GBS, 21 (43%) had the axonal electrophysiologic subtype, and 18% the demyelinating subtype. Evidence of recent C jejuni infection was found in 28/43 (65%). No evidence of recent arbovirus infection was found. Twenty-three cases vs 11 controls (OR 3.3, confidence interval [CI] 95% 1.2–9.2, p < 0.01) had IgM and/or IgA antibodies against C jejuni. Anti-GM1:phosphatidylserine and/or anti-GT1a:GM1 heteromeric complex antibodies were strongly positive in cases (92.9% sensitivity and 68.3% specificity). Genomic analysis showed that the C jejuni strains were closely related and had the Asn51 polymorphism at cstII gene.
Conclusions Our study indicates that the 2019 Peruvian GBS outbreak was associated with C jejuni infection and that the C jejuni strains linked to GBS circulate widely in different parts of the world.
CHIKV=
chikungunya virus;
DENV=
dengue virus;
EGRIS=
Erasmus GBS Respiratory Insufficiency Score;
GBS=
Guillain-Barré syndrome;
GBSDS=
Guillain-Barré syndrome Disability Score;
HC=
healthy control;
HCH=
Hospital Cayetano Heredia;
LOS=
lipo-oligosaccharide;
mEGOS=
modified Erasmus GBS Outcome Score;
MRC=
Medical Research Council;
mRS=
modified Rankin Scale;
NCBI=
National Center for Biotechnology Information;
NCS=
nerve conduction study;
PS=
phosphatidylserine;
ROC=
receiver operating characteristic;
ST=
sequence type;
ZIKV=
Guillain-Barré syndrome (GBS) is an immune-mediated disorder frequently triggered by infections, characterized by an acute flaccid paralysis, accompanied by sensory symptoms and cranial nerve deficits.1 In recent years, several outbreaks of GBS have been observed globally, including the large outbreaks in Latin America during the Zika virus (ZIKV) epidemic,2,–,4 and the possibility of an association between severe acute respiratory syndrome coronavirus 2 infection and GBS has been raised.5 As the ZIKV epidemic transitioned to an endemic phase in the Americas in 2017, 2 major outbreaks of GBS occurred in Peru in 2018 and 2019. The number of reported GBS cases increased from 59 in 2017 (incidence: 0.19/100,000) to 262 in 2018 (incidence: 0.81/100,000) and 1,120 in 2019 (incidence: 3.44/100,000).6 During these outbreaks, the increases in GBS cases were also reported in areas where there is no potential arboviral transmission, such as the highlands of Peru. The outbreaks had a seasonal pattern with the major peaks occurring between April and July in both years (figure 1A).6,7 We investigated the causality of these outbreaks, by performing an observational clinical cohort study of adult patients with GBS evaluated at a tertiary university hospital in Lima during the 2019 outbreak.
Figure 1 Epidemiologic Profile of 2018–2019 Guillain-Barré Syndrome (GBS) Outbreaks in Peru
(A) Epidemiologic curves (2018–2019) of GBS cases in Peru based on Peruvian Ministry of Health data.6 (B) Map of Peru shows regions of origin of GBS cases included in the study. Cajamarca, Huaraz (Ancash), and Huancavelica are cities located in the highlands where no arbovirus transmission was reported.
Study Population and Design
We prospectively evaluated the clinical and laboratory features of patients suspected of GBS at the Hospital Cayetano Heredia (HCH), a university-based tertiary care hospital in Lima, Peru, during the 2019 GBS outbreak (May–August) in Peru. We included all patients who were evaluated by a neurologist and fulfilled the Brighton Collaboration Working Group criteria for diagnosis of GBS with a classification level 1, 2, or 3.8 Included patients underwent neurologic evaluation during the acute and convalescent phase of their illness and were followed up to 6 months after discharge. Patients with alternative diagnoses or insufficient data were excluded. Blood, CSF, respiratory, and stool samples were obtained during the acute phase as part of the standard of care to identify potential infectious etiologies. Nerve conduction studies (NCSs) and EMG were performed and classified according to the criteria of Hadden et al.9,10 The clinical and laboratory information was documented using standardized questionnaires of the Neuroviruses Emerging in the Americas Study forms adapted from the International GBS Outcome Study.3,11
The onset of GBS and disease nadir were defined as the first day of neurologic symptoms and the most severe clinical weakness, respectively. Pure motor GBS was defined as limb weakness in the absence of sensory deficits at neurologic examination, and sensorimotor GBS was defined as presence of both limb weakness and sensory deficits. Limb muscle strength was evaluated using the Medical Research Council (MRC) sum score.12 Severity was assessed according to the modified Rankin Scale (mRS),13 the GBS Disability Score (GBSDS),14 the modified Erasmus GBS Outcome Score (mEGOS),15 and the Erasmus GBS Respiratory Insufficiency Score at admission (EGRIS).16
Hematologic and comprehensive metabolic assessments, including among others sodium and potassium levels, liver and kidney function tests, and HIV serology, were performed in all patients at admission. For the investigation of infectious agents, blood, CSF, oropharyngeal swabs, and stool samples were tested at the Naval Medical Research Unit 6 in Lima, Peru. Blood samples were assessed for arboviral infections including ZIKV, dengue virus (DENV), and chikungunya virus (CHIKV) using quantitative real time-PCR.17 Oropharyngeal swabs were tested for 20 respiratory pathogens using a multiplexed PCR assay (BioFire Diagnostics, Salt Lake City, UT). Stool swabs in Cary Blair medium were analyzed using a multiplexed PCR assay for gastrointestinal pathogens (BioFire Diagnostics), which included 22 pathogens associated with gastroenteritis, such as Campylobacter species (jejuni, coli, and upsaliensis), and Escherichia coli. Stool samples were cultured for identification and characterization of E coli and C jejuni.18 Positive culture samples were further characterized using multiplexed PCR assays for identification of C jejuni19 and Penner types.19,20 C jejuni isolates from stool cultures were sequenced using next-generation sequencing techniques, and the genomic assemblies underwent genomic and phylogenetic analysis based on the hypervariable lipo-oligosaccharide (LOS) region. Phylogenetic analysis was based on 83 C jejuni genome assemblies from the National Center for Biotechnology Information (NCBI), which included all 16 genomes reported to be associated with GBS in the NCBI metadata and 67 additional genomes selected to represent a wide range of the collection locations, dates, and studies available (appendix e-1, links.lww.com/NXI/A403). These 83 genomes, the C jejuni reference genome (NCTC11168),21,22 and the 4 genomes of 4 C jejuni isolates assembled from the present study were used to construct a phylogenic tree from the sequence of the hypervariable LOS biosynthesis gene locus using the Nextstrain-Augur pipeline.23
To evaluate the association between C jejuni infection and GBS, serum samples from 42 GBS cases were compared with serum samples of 41 controls for the presence of anti–C jejuni IgA, IgM, and IgG antibodies by ELISA following a case-control methodology.24 Control samples were obtained from subjects from the same or neighboring households of the patients with GBS. The controls were evaluated by a neurologist to exclude a history of weakness within the previous year and to document normal neurologic status. The presence of anti–C jejuni antibodies was expressed as a ratio of optical density between a test sample and the cutoff serum sample. A ratio > 1.0 for IgM or IgA was considered evidence of a recent C jejuni infection. Concomitant C jejuni infection was defined as a positive Campylobacter PCR in a stool sample or by stool culture.
Case-control methodology was also used to study antiganglioside immunity using a multiplexed array panel to identify specific antiganglioside IgG antibodies. Patient and control sera were screened on microarrays.25 Glycolipid microarrays consisted of a panel of 16 single glycolipids, the majority of which are gangliosides (GM1, GM2, phosphatidylserine [PS], GM4, GA1, GD1a, GD1b, GT1a, GT1b, GQ1b, GD3, SGPG, LM1, GalNAc-GD1a, GalC, and sulfatide) and 120 heteromeric 1:1 (v:v) complexes printed in duplicate. The presence of antiglycolipid antibodies was determined using human IgG isotype-specific, fluorescent-conjugated secondary antibodies, and its intensity was measured on a scale of 0–65,535 using a Genepix 4300A (Molecular Devices, San Jose, CA) microarray scanner. Antibody intensity values were reported as the average of duplicate median fluorescent intensity values per sample. Results were graphically displayed as heat maps using Pearson correlation hierarchical clustering (MeV software). The optimal cutoff value for antiglycolipid IgG antibodies, above baseline levels, was calculated from receiver operating characteristic (ROC) curves using Youden index.
The clinical and laboratory findings were described using absolute and relative frequencies. Median and interquartile ranges (IQRs) were reported for quantitative variables. The χ2 or Fisher exact test, OR, and 95% CIs were used to determine differences between the groups. A p value <0.05 was considered significant. Area under the curve was calculated for each antiglycolipid antibody combination in ROC analysis. Statistical analyses were performed using Stata software, V15.0 (College-Station, TX).
This study was reviewed and approved by the HCH Institutional Review Board. All patients (or relatives when patients were incapacitated) and healthy controls (HCs) provided written informed consent.
All data reported within the article are available anonymized on reasonable request by qualified investigators.
Fifty-nine patients suspected of GBS were seen between May and August 2019. Ten were excluded: 8 had insufficient data due to transfer to other hospitals during the outbreak, 1 patient had a recent infection with HIV, syphilis and tuberculosis, and 1 patient had only cranial nerve involvement. Of the 49 included patients, 43 were from Lima city and 6 from Northern area and highlands of Peru (figure 1B). The demographic and clinical characteristics of the 49 patients are described in table 1. All patients fulfilled Brighton criteria level 1 (84%) or level 2 (16%). The median age was 44 years (IQR 30–54 years), and 28 (57%) were male. Thirty-two patients (65%) had symptoms of an infection 6 weeks preceding the onset of GBS: 24 (49%) diarrhea and 13 (27%) upper respiratory tract symptoms, and 2 patients (4%) received an influenza vaccine. The median time from onset of infectious to neurologic symptoms was 3 days (IQR 2–9 days), and the time from onset of neurologic symptoms to nadir was 6 days (IQR 3–7 days). At admission, all patients reported limb weakness. Quadriparesis evolving in less than 24 hours from neurologic symptom onset was observed in 5 patients (10%). The median GBSDS at admission was 4 (IQR 3–4), and EGRIS was 3 (IQR 2–4). Fifteen patients (31%) had cranial neuropathy, with the facial nerve most commonly involved. The median MRC sum score was 42 (IQR 26–50). Most patients (80%) were classified clinically as pure motor GBS. Neurologic examination, treatment, and outcome at nadir and at 6-month follow-up are detailed in table e-1 (links.lww.com/NXI/A406).
Demographic and Clinical Characteristics of Patients With GBS
NCSs/EMG studies were performed in all patients at a median of 16 days after onset of neurologic symptoms (IQR 10–23 days). Twenty-one patients (43%) had axonal neuropathy (acute motor axonal neuropathy), 9 (18%) demyelinating neuropathy (acute inflammatory demyelinating polyneuropathy), 8 (16%) equivocal, 5 (10%) inexcitable, and 6 (12%) had normal studies.
Forty-seven patients (96%) received treatment with IVIg (51%), plasmapheresis (18%), or both (27%). The standard treatment was 5 sessions of plasmapheresis or 0.4 mg/kg/d IVIg for 5 days. IVIg treatment was stopped in 1 patient who developed angioedema during their second session and who died before starting plasmapheresis. Two patients did not receive treatment, 1 because of lack of treatment availability on admission and 1 due to initial misdiagnosis. Both patients improved without treatment. Thirteen patients (27%) were admitted to the intensive care unit, 12 (24%) required ventilatory support, and 6 (12%) had cardiac dysautonomia. The median hospitalization time was 14 days (IQR 9–23 days).
One week after admission, the median mEGOS was 5 (IQR 2–9). Most patients improved as indicated by mRS score at 6-month follow-up (median 2, IQR 1–2) compared with nadir (median 4, IQR 4–5). Four patients (8%) died. The most common sequela after 6 months was neuropathic pain (69%) (table e-1, links.lww.com/NXI/A406).
Hematologic and biochemical testing at admission were normal in all cases. CSF examination was performed in 48/49 patients at a median of 5 days (IQR 4–7 days) after start of neurologic symptoms. All patients had normal cell counts (median 0, IQR 0–1), and 14 (29%) had an increased protein level (>52 mg/dL) (table 1).
Laboratory results for infectious agents and antiganglioside profiles are described in table 2. One patient with known HIV infection was HIV positive. Twenty (41%) patients underwent testing for ZIKV, 26 (53%) for DENV, and 22 (45%) for CHIKV, and all were negative. Nineteen patients (39%) underwent testing by Film Array respiratory panel, and 5 (26%) were positive for common respiratory viruses not known to be associated with GBS (table 2).
In 43 patients (88%), biosamples were available for C jejuni infection testing with either molecular or serologic assays or stool cultures (table e-2, links.lww.com/NXI/A407). In 23/42 (55%) patients, anti-C jejuni IgM and/or IgA antibodies were found, of whom 9 also tested positive for Campylobacter sp PCR in stool. In contrast, only 11/41 (27%) controls had evidence of anti-C jejuni IgM or IgA (OR: 3.3, CI 95% 1.2–9.2, p < 0.01) (table 2).
The PCR-based gastrointestinal panel showed that 14/37 (38%) patients had evidence of Campylobacter sp genome. Stool cultures from 4 of these patients grew bacteria, which were confirmed as C jejuni by immunologic and molecular assays (table 2, table e-2, links.lww.com/NXI/A407). Penner molecular typing indicated that these isolates were all HS41 capsule type. Genomic analysis showed that these strains were clonal, sequence type (ST) ST2993, with class A LOS biosynthesis locus, a pathogenicity island that contains genes with the potential to generate LOS that mimic human gangliosides. Phylogenetic analysis showed that of the 20 GBS-associated C jejuni genomes, 15, including the 4 isolates from this study, have LOS regions fairly closely related to one another and to other strains of C jejuni associated with GBS isolated in China and Africa (figures 2 and 3). Sample collection regions do not appear to define clades, with strains from countries with numerous samples spread throughout the tree. All 4 C jejuni isolates from our study had the Asn51 polymorphism at cstII gene (figure e-1, links.lww.com/NXI/A404) based on the alignments to ICDCCJ07001 indicating the capability to synthesize both alpha 2–3 and alpha 2–8 sialic acid linkages on their LOS core oligosaccharide.26,27 The genomes of these 4 C jejuni isolates were deposited at NCBI within BioProject PRJNA643291 (accession numbers SAMN15508151, SAMN15508152, SAMN15508153, and SAMN15508154, ncbi.nlm.nih.gov/bioproject/PRJNA643291).
Figure 2 Phylogenetic Tree of Campylobacter jejuni Isolates in GBS
Phylogenetic tree built from the lipo-oligosaccharide region of 88 C jejuni species using the Nextstrain pipeline, colored by region. The 4 Peruvian strain assemblies are indicated. The tree was built via alignment to the ICDCCJ07001 strain and then rooted by inferring ancestral states. GBS = Guillain-Barré syndrome.
Figure 3 Phylogenetic Map of Campylobacter jejuni Isolates in Guillain-Barré Syndrome (GBS)
Map distribution of strains depicted in the phylogenetic tree. Strains are colored by region of collection, which was available for all but 2 genomes, the C jejuni reference, NCTC11168, and 1 GBS-associated strain, G1, which had no listed collection location. The size of the circles within countries on the associated world map is proportional to how many samples are included from that country.
Combining serologic assay and stool PCR, 28/43 patients (65%) had evidence of recent C jejuni infection (table 2, table e-2, links.lww.com/NXI/A407). Of interest, these 28 patients did not significantly differ in the time to nadir, clinical variants, or electrophysiologic subtypes to the 15 patients without evidence of a recent C jejuni infection (table e-2). Patients with evidence of a recent C jejuni infection had a higher percentage of preceding gastrointestinal symptoms, although this was not significant (43% vs 27%, p = 0.69). Other preceding infectious symptoms were also not significantly different.
Antiganglioside IgG antibodies of differing specificities were detected in a high proportion of cases compared with HCs (figure e-2, links.lww.com/NXI/A405). Summarizing this overview heatmap, 2 broad populations of IgG antibodies were dominantly present in this cohort: those reactive with GM1 alone or in complexes and those reactive with GT1a, alone or in complexes (table 2, figure 4). A smaller number of samples contained antibodies to GalNAc-GD1a alone or in complexes. Antibodies to other gangliosides including GM2, GD1b, GD1a, and GT1b and to myelin glycolipids including SGPG, LM1 and GalC were either very infrequently or not observed. Ganglioside antigens were probed as single molecules and when in heteromeric complex (1:1 ratio) with one other ganglioside or lipid. This use of complexes is known to enhance antiganglioside antibody signals in a proportion of serum samples.28 To identify the enhanced binding intensities resulting from complexes, samples were probed against GM1 and GT1a in complex with other lipids (figure 4A). Results were then analyzed and displayed using ROC curve analysis in which the true and false-positive rates are calculated at various threshold settings to generate sensitivity and specificity data for the assay. ROC data for the major targets are shown in figure 4, B and C and figure e-2B and C. Using this approach, GM1 ganglioside in a 1:1 heteromeric complex ratio with PS or GT1a ganglioside proved to be the most significant diagnostic marker. When GM1 was in complex with PS, antibodies to the GM1:PS complex returned a sensitivity 78.6% and a specificity of 78.0% for GBS (figure e-2B). When GM1 was in complex with GT1a, antibodies to the GM1:GT1a complex returned a sensitivity of 81.0% and a specificity of 80.5% for GBS (figure 4B). The enhancing effect, as manifested by an increase in fluorescence intensity units, of GM1 in complex with GT1a vs either antigen alone is shown in figure 4C. In contrast, the GM1:GalNAc-GD1a complex did not enhance reactivity with either glycolipid alone (figure e-2C). When selecting the GM1:PS and GT1a:GM1 complex antigen targets as biomarkers of GBS, 92.9% of patients had IgG antibodies to one or both of these glycolipid complexes compared with 31.7% of HCs.
Figure 4 Antiganglioside Antibody Binding Profile in Peruvian GBS Cases
Graphical displays of GBS and healthy control (HC) serum IgG antiganglioside antibody binding. (A) Heat maps illustrating the IgG binding intensity to 3 single glycolipids and 4 heteromeric complex antigen targets in GBS cases (upper map, n = 42) and HC sera (lower map, n = 41). Each horizontal row refers to the IgG binding reactivity of an individual GBS or HC serum sample, and each vertical row refers to each of the 7 targets displayed. The rainbow bar denotes the intensity scale of IgG binding from low (blue) to high (red) intensity. Two patterns of reactivity are greatly amplified by presenting glycolipids/lipids targets as heteromeric complexes compared with binding to each target alone: GM1:GT1a complex (first column *) and GM1:PS complex (fourth column **). Note that these 2 patterns of heteromeric complex reactivity do not substantially overlap within any 1 patient, being mutually exclusive. (B) An illustrative receiver operating characteristic (ROC) curve comparing the sensitivity and specificity of GT1a and GM1 as single glycolipids with the GT1a:GM1 heteromeric complex. The highest sensitivity (81%) and specificity (80.5%) are seen with the GM1:GT1a complex. (C) IgG reactivity values of each individual patient are plotted for the same 3 antigen targets (GM1, GT1a, and GM1:GT1a complex) subjected to ROC analysis in panel B. Greatly enhanced binding intensity to the GT1a:GM1 heteromeric complex compared with the sum of the single glycolipid antigens is present in most samples. GBS = Guillain-Barré syndrome; PS = phosphatidylserine.
In the aftermath of the ZIKV epidemic in Latin America, that was associated with significant increases in the incidence of GBS, 2 large seasonal outbreaks of GBS occurred in Peru in 2018 and 2019.6,29 Our study, describing a large cohort of patients and controls during the 2019 GBS outbreak in Lima, Peru, demonstrates that this outbreak was associated with C jejuni infection, a diarrheal bacterium that is the most common trigger of GBS worldwide. As the outbreak of GBS in 2018 occurred in the same season and regions of the country (figure 1B), this outbreak was likely related to C jejuni as well. Because stricter public health measures were instituted in Peru, after the first COVID-19 case in March 2020, GBS incidence decreased to less than 0.27/100,000.6
We found evidence of recent C jejuni infection in 28/43 patients (65%), of whom 9 were positive for Campylobacter sp PCR in stool. Other preceding infections previously associated with GBS, including Mycoplasma pneumoniae, DENV, CHIKV, and ZIKV, were negative in all tested cases. Recent C jejuni infection was significantly more likely to occur in GBS cases (23/42, 55%) compared with controls (11/41, 27%, OR: 3.3, p < 0.01). Of interest, the proportion of controls with a recent C jejuni infection was high (27%), which may be indicative of an ongoing outbreak of C jejuni, although our study was not designed to investigate this. This high percentage may also be in part due to overmatching of cases and controls or a high prevalence of C jejuni in Peru, as has been indicated by previous serosurveillance studies.30,31 Notably, the vast majority of C jejuni infections, even when bearing ganglioside mimics in their LOS, manifest as uncomplicated enteritis and are not associated with the development of GBS. Genomic analysis of C jejuni isolates showed that they have closely related LOS regions to one another and to previously described GBS-associated C jejuni genomes from China and Africa reported in the past 2 decades, suggesting that these strains were introduced or reemergent infections from an endemic reservoir rather than being new emergent strains.32,–,34
Besides the laboratory evidence, the clinical and electrophysiologic profile is typical for C jejuni–associated GBS as described in previous studies.9,35,36 The majority of cases had a preceding diarrheal illness, followed by an early-onset, rapidly progressive pure motor axonal GBS. This profile is in contrast to the clinical profile that has been reported in association with ZIKV or COVID-19, where most patients have facial palsy, sensory and motor deficits, and a demyelinating electrophysiologic subtype.37,38
However, there was not a uniform relationship between C jejuni serotype and clinical, electrodiagnostic, and antiganglioside profile. This may be due to methodological factors that prevent unambiguous case definition and ascertainment. For example, CSF examination and electrodiagnostic studies are not always sensitive diagnostic tools in GBS, especially when done early in the disease course. This may have resulted in only 29% of patients having an increased protein level in CSF, or inaccurate classification of electrophysiologic studies as axonal or demyelinating.8,39 The time between onset of systemic and neurologic symptoms (median 3 days, IQR 2–9 days) was also shorter than expected based on previous studies, which may be due to the wide range of the incubation period of C jejuni (1–10 days); patients only reporting symptoms when they become severe; or the presence of a parainfectious rather than postinfectious mechanism, as previously reported in ZIKV-related GBS.3,40 Another surprising finding was the high percentage (27%) of cases with diarrhea in the group without evidence of a recent C jejuni infection. This may due to the presence of other infections able to trigger GBS that may lead to gastrointestinal symptoms or low sensitivity of the standard serologic testing method for recent C jejuni infection (presence of IgM antibody) in a population where the incidence of infection, as indicated by the universally positive IgG serology, is very high. Notwithstanding previous studies that show diarrhea has been associated with a poor prognosis, the percentage of our patients able to walk at 6 months was high (82%), although we did find that diarrhea was more frequent (67% vs 45%) in patients with worse outcome, as defined by mRS score ≥ 4 at 6 months.35,41
The antiganglioside antibody profile, with strong positivity for GM1 and anti-GT1a, as single antigens or in complex, is similar to what has previously been found in post–C jejuni GBS in other parts of the world and lends strong support that these patients represent the typical immune phenotype seen in C jejuni–associated GBS.42,–,44 The use of complexes of GM1 and GT1a with each other or other lipids (herein PS) greatly enhanced the sensitivity of antibody detection in this cohort. The significant presence and high frequency of antiganglioside antibodies lends strong evidence to the conclusion that molecular mimicry between Campylobacter LOS and gangliosides is the immunopathologic driver of this form of GBS in Peru. The high prevalence of anti-GT1a antibodies in this groups is consistent with the cstII polymorphism (Asn51) seen in this study and similar to that observed in a GBS outbreak in China.45
The main limitation of our study is that we were not able to perform complete laboratory studies in all patients and controls as the study was conducted in the context of an emerging outbreak. We were able to exclude other preceding infections, including arboviruses, in 53% of cases and completed the serologic case-control study in 86% of cases. It is unlikely that different results would have been obtained had all subjects been tested.
In conclusion, we showed that C jejuni, and not ZIKV as was initially thought, was the infectious driver of the 2019 GBS outbreak in Peru, and the clinical, electrophysiologic, and immunologic profile was consistent with C jejuni–related GBS. The C jejuni strains were likely introduced or reemergent infections from an endemic reservoir and not new emergent strains. This finding has global relevance as it indicates that the C jejuni strains linked to GBS circulate widely in different parts of the world. This shows that researchers should remain aware of C jejuni as a trigger for GBS when investigating the association between other infections, including COVID-19, and GBS. Reinforcing public health measures, including setting up campylobacteriosis and GBS surveillance, to rapidly identify new epidemics, pathologic strains, and sources of transmission should be encouraged to prevent future outbreaks.30,31,46
Laboratory and research studies were funded in part by Global Emerging Infections Surveillance (M. Grogl); ZikaPLAN, European Union's Horizon 2020 research and innovation programme under Grant Agreement No. 734584 (B.C. Jacobs, H.J. Willison), and the Wellcome Trust, Grants 092805 and 202789 (H.J. Willison) and NIH R01 NS110122 (C.A. Pardo). The funding resources did not have any role in the writing of the manuscript or the decision to submit for publication.
A.P. Ramos, S.E. Leonhard, S.K. Halstead, M.A. Cuba, C.C. Castañeda, J.A. Dioses, M.A. Tipismana, J.T. Abanto, A. Llanos, and D. Gourlay report no disclosure relevant to the manuscript. M. Grogl, M. Ramos, J.D. Rojas, and R. Meza are employees of the US Government. This work was prepared as part of our official duties. Title 17, U.S.C., §105 provides that copyright protection under this title is not available for any work of the US Government. Title 17, U.S.C., §101 defines a US Government work as a work prepared by a military service member or employee of the US Government as part of that persons official duties. The views expressed in this article reflect the results of research conducted by the authors and do not necessarily reflect the official policy or position of the Department of the Navy, Department of Defense, or the US Government. D. Puiu, R.M. Sherman, S.L. Salzberg, P.J. Simner, and H.J. Willison report no disclosure relevant to the manuscript. B.C. Jacobs receives unrestricted funding for research from Prinses Beatrix Spierfonds, GBS-CIDP Foundation International, CSL Behring, Grifols, Annexon, and Hansa Biopharma. D.R. Cornblath has received consultancy honoraria from Mitsubishi Tanabe Pharma Corporation, Alnylam Pharmaceuticals, Inc., Hansa Medical Ab, Pledpharma, Momenta Pharmaceuticals, Inc., CSL Behring, Sanofi Aventis Recherche & Developpement, Pfizer Inc., Seattle Genetics Inc., Octapharma Ag, Grifols, S.A., Cigna Corporation, Pharnext SA, Annexon Biosciences, UCB Pharma Inc., Boehringer Ingelheim, Biotest Pharmaceuticals, Inc., Argenx, Cytomx Therapeutics, Passage Bio Pharma, Seattle Genetics Inc., Astra Zeneca Pharmaceuticals Lp, Genentech Corp, Merrimack Pharmaceuticals, Disarm Therapeutics, Inc., Levicept Ltd., and Amgen Inc. Johns Hopkins University has the rights to The Total Neuropathy Score© for which D.R. Cornblath receives royalty payments. H.F. Umeres and C.A. Pardo report no disclosure relevant to the manuscript. Go to Neurology.org/NN for full disclosures.
The authors are grateful to Drs. Aida Palacios and Wilde Lavado for their continuous support during the Peruvian GBS outbreak in Hospital Cayetano Heredia; Maria Bernal and Enrique Canal for their technical assistance in laboratory; and Dr. Kiran Thakur for their support for the project.
↵* These authors contributed equally to this work and are co–senior authors.
The Article Processing Charge was funded by ZikaPLAN.
Accepted in final form November 23, 2020.
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redpajama_set_name: RedPajamaCommonCrawl


text:
Swap Execution Facility (SEF): Definition, Goal and How It Works
Reviewed by Andy Smith
What Is a Swap Execution Facility (SEF)?
A Swap Execution Facility (SEF) is an electronic platform provided by a corporate entity that allows participants to buy and sell swaps in a regulated and transparent manner. They are required by law as part of the sweeping Wall Street reforms stemming from the 2010 Dodd-Frank Act.
Swap execution facilities (SEFs) are trading platforms intended for swaps products.
They are mandated under the Dodd-Frank Wall Street Reform Act of 2010.
Because of the complex nature of swaps, these platforms are not exchanges per se but they do function as a counterparty matching service.
Swaps traded on SEFs fall under the oversight of both the SEC and CFTC.
Swaps volume has increased over the years and now dozens of entities provide SEF platforms.
Understanding Swap Execution Facility
A SEF is an electronic platform that matches counterparties in a swaps transaction. Through a mandate in the Dodd-Frank Wall Street Reform and Consumer Protection Act, SEFs changed the methods previously used to trade derivatives.
The Dodd-Frank Act defined a SEF as, "A facility, trading system or platform in which multiple participants have the ability to execute or trade swaps by accepting bids and offers made by other participants that are open to multiple participants in the facility or system, through any means of interstate commerce."
Before Dodd-Frank, swaps were traded exclusively in over-the-counter (OTC) markets with little transparency or oversight. The SEF allows for transparency and provides a complete record and audit trail of trades.
The Securities and Exchange Commission (SEC) and the Commodity Futures Trading Commission (CFTC) regulate SEFs.
An Exchange for Swaps
A SEF is similar to a formal exchange but is a distributed group of approved trading systems. The handling of trades is similar to other exchanges. Also, the Dodd-Frank Act states if no SEF system is available for specific swaps, then the previous, OTC trading method, is acceptable.
Proponents argue that a SEF is a swaps exchange, much like a stock or futures exchange, and they are correct, to a degree. Centralized clearing of swaps and other derivatives reduces counterparty risks and increases trust and integrity in the marketplace. Also, a facility that allows for multiple bids and offers provides liquidity to the swap marketplace. This liquidity enables traders to close positions ahead of contract maturity.
Becoming a Swap Execution Facility
Many entities may apply to become a SEF. To qualify, they must meet specific thresholds as defined by the SEC, CFTC, and the Dodd-Frank Act.
Applicants must register with the SEC and meet specific requirements. Requirements include the platform's ability to display all available bids and offers, send trade acknowledgments to all involved parties, maintain a record of transactions, and provide a request for quote (RFQ) system. In addition, they must meet certain margin and capital guidelines and the ability to segregate the swap exchange. Finally, the applicant must agree to abide by the 14 SEC core principles.
An SEF can become "dormant" if it has not carried out a swap execution in more than 12 months. A dormant SEF must re-register to become active again.
How does a swap execution facility work?
Swap execution facilities (SEFs) are electronic matching platforms that bring together buyers and sellers of swaps contracts, much like any other electronic exchange. These are regulated venues that rely on a request-for-quote mechanism.
Why were swap execution facilities created?
Swap execution facilities were created under the 2010 Dodd-Frank act to better regulate and increase transparency for swaps deals, both before and after the trade.
Who must register with an SEF?
According to the CFTC, "any person who offers a trading system or platform in which more than one market participant has the ability to execute or trade swaps with more than one other market participant on the system or platform must apply to the Commission to register as a SEF."
Are swaps required to be transacted through a swap execution facility?
While many swaps now must be traded on a SEF, financial institutions can still transact certain swaps over-the-counter (OTC) directly between one another. But, swap trades that are eligible to be cleared must use a SEF.
FIA. "Comparison Table." Accessed Jan. 12, 2022.
FIA. "Monthly Volume." Accessed Jan. 12, 2022.
CFTC. "Swaps Execution Facilities (SEFs)." Accessed Jan. 12, 2022.
Nasdaq. "SEFs Must Defend Against Market Abuse." Accessed Jan. 12, 2022.
Lynn Riggs, Esen Onur, David Reiffen, Haoxiang Zhu. "Swap Trading after Dodd-Frank: Evidence from Index CDS," Journal of Financial Economics Volume 137, Issue 3, September 2020, Pages 857-886. Accessed Jan. 12, 2022.
The Securities and Exchange Commission. "Derivatives." Accessed Jan. 12, 2022.
The Securities and Exchange Commission. "SEC Proposes Rules for Security-Based Swap Execution Facilities." Accessed Jan. 12, 2022.
Office of the Law Revision Counsel United States Code. "15 USC 78c-4: Security-Based Swap Execution Facilities." Accessed Jan. 12, 2022.
Federal Register. "Swap Execution Facility Requirements." Accessed Jan. 12, 2022.
The CFTC is an independent U.S. federal agency established by the Commodity Futures Trading Commission Act of 1974.
Commodity Futures Modernization Act (CFMA)
Commodity Futures Modernization Act (CFMA), passed in 2000, provided broad regulatory exemptions for over-the-counter derivatives.
Dodd-Frank Act: What It Does, Major Components, Criticisms
The Dodd-Frank Wall Street Reform and Consumer Protection Act is a series of federal regulations passed to prevent future financial crises.
National Futures Association (NFA): What It Is and Does
The National Futures Association (NFA) is an independent, self-regulatory organization for the U.S. derivatives industry. It identifies and mandates industry-best practices.
What Is an Amortizing Swap?
An amortizing swap is an interest rate swap where the notional principal amount is reduced at the underlying fixed and floating rates.
Swap Dealer
A swap dealer is an individual who acts as the counterparty in a swap agreement for a fee called a spread.
Rulemaking for Federal Agencies
Investing Regulations
Major Regulations Following the 2008 Financial Crisis
SEC Proposes Major Overhaul to Stock Trading Rules
Private Equity & VC
Private Equity Management Fees and Regulations
Introduction to Fiscal Policy
Sarbanes-Oxley vs. Dodd-Frank
Getting to Know the Stock Exchanges


text:
Composite Material can Cool itself Down Under Extreme Temperatures
Posted on November 5, 2018 0
A cutting-edge material, inspired by nature, that can regulate its own temperature and could equally be used to treat burns and help space capsules withstand atmospheric forces is under development at the University of Nottingham.
The research paper, Temperature – dependent polymer absorber as a switchable state NIR reactor, is published in the journal Scientific Reports today (Friday 26 October).
"A major challenge in material science is to work out how to regulate human-made material temperature as the human body can do in relationship to its environment," explains lead author Dr Mark Alston, Assistant Professor in Environmental Design, from the Faculty of Engineering.
The research used a network of multiple microchannels with active flowing fluids (fluidics) as a method and proof of concept to develop a thermally-functional material made of a synthetic polymer. The material is enhanced with precise control measures that can switch conductive states to manage its own temperature in relationship to its environment.
"This bio-inspired engineering approach advances the structural assembly of polymers for use in advanced materials. Nature uses fluidics to regulate and manage temperature in mammals and in plants to absorb solar radiation though photosynthesis and this research used a leaf-like model to mimic this function in the polymer."
Dr Alston adds: "This approach will result in an advanced material that can absorb high solar radiation, as the human body can do, to cool itself autonomously whatever the environment it is placed in. A thermally-functional material could be used as a heat regulation system for burn injuries to cool skin surface temperature and monitor and improve healing."
This kind of heat flow management could also prove invaluable in space flight where high solar loads can cause thermal stresses on the structural integrity of space capsules.
By regulation of the structural material temperature of the vehicle, this will not only advance structural properties but could also generate useful power. This thermal energy could be removed from the re-circulated fluid system to be stored in a reservoir tank on board the capsule. Once captured, the energy could be converted into electrical energy or to heat water for use by the crew.
The experimental side of this research is laboratory-based and has been developed in collaboration with UK Government research institute: Scientific Research Facilities Council (SRFC). The next steps for the research are to secure funding for a demonstrator scale-up to present to aerospace manufacturing and to identify an industrial partner.
Composite Material,fluidics,NIR Reactor,polymer absorber,University of Nottingham Articles,Blogs,Research and Development,Thermal Materials


It is sometimes difficult to know exactly what to say.
With that in mind, we are looking to help with words of celebration, thanks, condolence… and more.
Words, quotes and phrases that may help you find the inspiration to write the perfect message inside your cards.