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Biomedical subjects

K Schmid

Publications and source records attributed to K Schmid.

At least 19 recordsLinked to original sources
PubMed2006

Needlestick injuries and other occupational exposures to body fluids amongst employees and medical students of a German university: incidence and follow-up.

The aim of this study was to obtain data concerning the incidence, reporting and follow-up of occupational exposure to blood or other body fluids (OEB). A questionnaire was distributed to employees and medical students (N=787) and official reports of OEB during the year 2003 (N=203) and their consequent follow-up (N=100) were evaluated. The percentages of needlestick injuries were 29.5% for students and 22.5% for employees. Incidence rates per 1000 employee days were 0.61 for needlestick injuries or sharp object injuries and 0.27 for mucocutaneous exposure to body fluids. The mean rate of underreporting was approximately 45%. Contrary to expectations, only 4.3% of nurses and 3.9% of doctors officially reported an OEB in 2003. The number of persons who did not attend for a serological test increased during the follow-up period. Considering all documented test results, 35 out of 100 affected persons were lost to follow-up due to default of appearance. As a consequence, the employer should provide safety devices and enforce didactical interventions with practical training and incident reporting. Periodical occupational health medicals, including serological testing, should be mandatory for all employees, including medical students and student nurses. To increase compliance after OEB, a short follow-up period using improved laboratory tests requires further discussion.

Follow-Up Studies↗
PubMed2006

Investigations on safety of hyperthermic intraoperative intraperitoneal chemotherapy (HIPEC) with Mitomycin C.

AIMS: Previous safety monitoring of hyperthermic intraoperative intraperitoneal chemotherapy (HIPEC) with Mitomycin C (MMC) did not demonstrate any detectable safety hazard to the personnel. Nevertheless, those results have been discussed controversially because of the methodological problems employed in the evaluation of potential exposure. We re-evaluated possible safety hazards of HIPEC by applying different monitoring strategies. METHODS: We monitored air samples in the operation room during HIPEC. In addition, we measured MMC in plasma of the surgeon with a newly developed analytical method. All samples were analysed by HPLC-UV at 360nm. The permeability of the gloves was tested using two in vitro techniques: diffusion cells and a glass cell chamber. In-use and worst-case exposure scenarios were imitated for in vitro experiments. RESULTS: The analysis of the air samples (n=3) could not detect any MMC. We found no drug above the limit of detection (1microg MMC/L) in the plasma samples of the surgeons (n=5). A breakthrough of latex glove material was detected in only one (worst-case exposure scenario) of 40 diffusion cell experiments. CONCLUSIONS: Established methods of safety monitoring could not reveal any detectable risk on in-use exposure conditions. The wearing of doubled latex gloves should prevent the surgeon from dermal exposure to MMC during HIPEC.

Air Pollutants, Occupational↗
PubMed2006

[A young patient with portal and mesenteric vein thrombosis and Proteus syndrome].

In the 26th year of life a young woman suffered a portal and mesenteric thrombosis followed by portal hypertension with splenomegaly, esophageal varices and pancytopenia. After splenorenal shunt surgery and splenectomy hematologic parameters resolved rapidly. Also, she was suffering of Proteus syndrome, which is an extremely rare and sporadic hamartomatous disorder characterized by a variety of cutaneous and subcutaneous tumors including vascular malformations, several types of nevi, partial gigantism of the hands and/or feet and cystic visceral affections. It has been demonstrated that concurrence of several prothrombotic risk factors occur relatively often in patients with portal vein thrombosis. An extensive investigation of thrombophilic factors revealed reproduced high anti-beta2-glycoprotein I antibody titers together with mildly increased homocysteine levels. Other coagulation parameters were normal or negative. The presence of myeloproliferative moglobinuria was ruled out. Together with the history of recurrent superficial thrombophlebitis and portal vein thrombosis in the absence of other underlying diseases allowed for diagnosis of primary antiphospholipid syndrome being aggravated by hyperhomocysteinemia and vascular malformations caused by Proteus syndrome. Because of combined risk factors for further thrombembolisms permanent oral anticoagulant therapy was initiated.

Adult↗
PubMed2006

Generation of quasimonoenergetic electron bunches with 80-fs laser pulses.

Highly collimated, quasimonoenergetic multi-MeV electron bunches were generated by the interaction of tightly focused, 80-fs laser pulses in a high-pressure gas jet. These monoenergetic bunches are characteristic of wakefield acceleration in the highly nonlinear wave breaking regime, which was previously thought to be accessible only by much shorter laser pulses in thinner plasmas. In our experiment, the initially long laser pulse was modified in underdense plasma to match the necessary conditions. This picture is confirmed by semianalytical scaling laws and 3D particle-in-cell simulations. Our results show that laser-plasma interaction can drive itself towards this type of laser wakefield acceleration even if the initial laser and plasma parameters are outside the required regime.

Journal Article↗
PubMed2006

Relationships of feedlot feed efficiency, performance, and feeding behavior with metabolic rate, methane production, and energy partitioning in beef cattle.

Residual feed intake (RFI) is the difference between the actual and expected feed intake of an animal based on its BW and growth rate over a specified period. The biological mechanisms underlying the variation in feed efficiency in animals with similar BW and growth rate are not well understood. This study determined the relationship of feedlot feed efficiency, performance, and feeding behavior with digestion and energy partitioning of 27 steers. The steers were selected from a total of 306 animals based on their RFI following feedlot tests at the University of Alberta Kinsella Research Station. Selected steers were ranked into high RFI (RFI > 0.5 SD above the mean, n = 11), medium RFI (RFI +/- 0.5 SD above and below the mean, n = 8), and low RFI (RFI < -0.5 SD below the mean, n = 8). The respective BW +/- SD for the RFI groups were 495.6 +/- 12.7, 529.1 +/- 18.6, and 501.2 +/- 15.5 kg. Digestibility and calorimetry trials were performed on a corn-or barley-based concentrate diet in yr 1 and 2, respectively, at 2.5 x maintenance requirements. Mean DMI (g/kg of BW(0.75)) during the measurements for high-, medium-, and low-RFI groups, respectively, were 82.7 +/- 2.0, 78.8 +/- 2.6, and 81.8 +/- 2.5 and did not differ (P > 0.10). Residual feed intake was correlated with daily methane production and energy lost as methane (r = 0.44; P < 0.05). Methane production was 28 and 24% less in low-RFI animals compared with high- and medium-RFI animals, respectively. Residual feed intake tended to be associated (P < 0.10) with apparent digestibilities of DM (r = -0.33) and CP (r = -0.34). The RFI of steers was correlated with DE (r = -0.41; P < 0.05), ME (r = -0.44; P < 0.05), heat production (HP; r = 0.68; P < 0.001), and retained energy (RE; r = -0.67; P < 0.001; energy values are expressed in kcal/kg of BW(0.75)). Feedlot partial efficiency of growth was correlated (P < 0.01) with methane production (r = -0.55), DE (r = 0.46), ME (r = 0.49), HP (r = -0.50), and RE (r = 0.62). With the exception of HP (r = 0.37; P < 0.05), feed conversion ratio was unrelated to the traits considered in the study. Feeding duration was correlated (P < 0.01) with apparent digestibility of DM (r = -0.55), CP (r = -0.47), methane production (r = 0.51), DE (r = -0.52), ME (r = -0.55), and RE (r = -0.60). These results have practical implications for the selection of animals that eat less at a similar BW and growth rate and for the environmental sustainability of beef production.

Animal Feed↗
PubMed2005

The nonreplicating smallpox candidate vaccines defective vaccinia Lister (dVV-L) and modified vaccinia Ankara (MVA) elicit robust long-term protection.

Current smallpox vaccines are live vaccinia viruses that replicate in the vaccinee inducing immunity against the deadly disease smallpox. Replication resulting in virus spread within the host, however, is the major cause of severe postvaccinal adverse events. Therefore, attenuated strains such as modified vaccinia Ankara (MVA) or LC16m8 are candidates as next generation vaccines. These strains are usually grown in primary cells in which mass production is difficult and have an unknown protective potential in humans. Proven vaccine strains of defined origin and modern production techniques are therefore desirable. In this study, defective vaccinia virus (dVV) lacking a gene essential for replication (derived from the Lister vaccine in a complementing cell line) was compared with the Wyeth smallpox vaccine strain and with MVA in mouse animal models using cowpox and ectromelia virus challenge. Similar to MVA, prime-boost immunizations with defective vaccinia induced robust long-term immunity, suggesting it as a promising next generation smallpox vaccine.

Animals↗
PubMed2005

Renal accumulation and clearance of advanced glycation end-products in type 2 diabetic nephropathy: effect of angiotensin-converting enzyme and vasopeptidase inhibition.

AIMS/HYPOTHESIS: Renal accumulation of AGEs may contribute to the progression of diabetic nephropathy. We evaluated the effect of ramipril (a pure ACE inhibitor) and AVE7688 (a dual inhibitor of ACE and neutral endopeptidase) on renal accumulation of the advanced glycation end-product (AGE) 3-deoxyglucosone-imidazolone, carboxymethyllysine (CML) and pentosidine, and on clearance of CML in type 2 diabetes. METHODS: Male Zucker diabetic fatty rats (ZDF, Gmi-fa/fa) rats were treated from age 10 to 37 weeks with ramipril (1 mg.kg(-1).day(-1)), AVE7688 (45 mg.kg(-1).day(-1)) or without drug. Ramipril and AVE7688 reduced albuminuria by 30 and 90%, respectively. RESULTS: ZDF rats showed increased renal accumulation of the AGE subtypes 3-deoxyglucosone-imidazolone, pentosidine and CML by about 40, 55 and 55%, respectively compared with heterozygous, non-diabetic control animals at the age of 37 weeks. AVE7688 but not ramipril attenuated the renal accumulation of 3-deoxyglucosone-imidazolone, pentosidine and CML and improved CML clearance in ZDF rats. During glycation reactions in vitro, AVE7688 also demonstrated potent chelating activity and inhibited metal-catalysed formation of pentosidine and CML. CONCLUSIONS/INTERPRETATION: Improved AGE clearance and direct inhibition of AGE formation by chelation may contribute to reduced accumulation of renal AGEs and to the nephroprotective effects of vasopeptidase inhibition in type 2 diabetes.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2005

[What do medical students know about their vaccination status and how effective is their vaccine protection?].

OBJECTIVE: Aim of this study was to inform medical students of existing deficits in their vaccination status and to raise their attention to the importance of vaccinations. METHODS: The status of vaccination was evaluated systematically in medical students (n = 1100, 686 (62.4 %) female). The students were asked to answer questions about their immunization history without consulting their vaccination certificates. Their answers were verified in their vaccination records. RESULTS: 86.2 % were in possession of their vaccination certificates. The ignorance about the vaccination status was smallest for mumps (9 %) and largest for pertussis (61 %). If data were given, these were frequently not confirmed. Immunization rates were 38.7 % (measles), 28.9 % (mumps), 29.6 % (German measles), 84.0 % (tetanus), 79.0 % (diphtheria) and 98.4 % (basic immunization against polio), 33.2 % (hepatitis A) and 63,7 % (hepatitis B). CONCLUSIONS: There is lacking awareness of vaccination in medical students. Memory data were not reliable. A preclinical occupational health medical examination with a strong focus on infectious diseases and vaccinations is important. Medical students would thus be able to appreciate the importance of immunizations. An increased awareness of vaccinations can improve the prevention of infectious diseases.

Adult↗
PubMed2005

Optical coherence tomography guided retreatment of photodynamic therapy.

AIM: To evaluate the results of a retreatment modality of photodynamic therapy (PDT) based on optical coherence tomography (OCT) and fluorescein angiography (FA). To quantify the effect of PDT with the help of measurement of the retinal thickness. METHODS: Eyes with predominantly classic subfoveal choroidal neovascularisation (CNV) due to age related macular degeneration were included. PDT was performed every three months, when needed. OCT, FA, and measures of distance acuity were performed at baseline, after 6 weeks, 3 months, and from then on every 3 months. A control group of a consecutive series of eyes that had been retreated based only on FA results was installed. RESULTS: Forty eyes of 38 patients were included. The average age was 73 years. The maximum retinal thickness decreased from 404 mum at baseline to 281.6 mum at month 12. Furthermore there was a significant decrease of retinal thickness in both subgroups. The number of retreatments was reduced, when activity was diagnosed using OCT and FA. (2.4 v 4.0). The distance acuity correlated significantly with the maximum retinal thickness (p=0.0042). CONCLUSION: Information about the activity of a neovascular lesion can be obtained with the help of OCT. The retreatment modalities can be optimised by using OCT and FA and the number of retreatments can be reduced.

Aged↗
PubMed2005

Beam mixing with a pinhole.

After a small aperture the spatial information of a complex optical wavefront is lost, but amplitude and phase information is mixed and transferred to the smoothed wave that emerges from the pinhole. This mixing effect is described in the case of a wavefront with a phase step, which is shifted over the input plane of an optical processor with a pinhole as spatial filter in the Fourier plane. We constructed a polarizing interferometer to demonstrate this continuous phase shift and show that it can be used as a variable retardation wave plate similar to a birefringent compensator, but without crystalline wedges.

Journal Article↗
PubMed2004

Early detection of diabetes retinopathy by new algorithms for automatic recognition of vascular changes.

Diabetes mellitus often results in diabetic retinopathy caused by pathological changes of the retinal vessel tree. Early detection of these changes can delay the disease. Image processing can reduce the workload of screeners and can play a central role in quality assurance tasks. Therefore we aimed at the refinement and development of image processing algorithms to improve the quality and cost effectiveness of screening and diagnosis of diabetic retinopathy. In order to support ophthalmologists in their routine and to enable the quantitative assessment of vascular changes in colour fundus photographs a multi-resolution approach was developed which segments the vessel tree efficiently and precisely into digital images of the retina. The vessel tracker aims at determining as correctly as possible the retinal vascular network captured on a digital image irrespective of its origin. In addition to the tracker, algorithms were developed to detect the optic disk, bright lesions such as cotton wools spots, and dark lesions such as haemorrhages. The following classification of veins and arteries identifies arteries in 78.4 % and veins in 66.5% correctly. This helps selecting conspicuous images from a great number of patients.

Algorithms↗
PubMed2004

The genes and enzymes for the catabolism of galactitol, D-tagatose, and related carbohydrates in Klebsiella oxytoca M5a1 and other enteric bacteria display convergent evolution.

Enteric bacteria (Enteriobacteriaceae) carry on their single chromosome about 4000 genes that all strains have in common (referred to here as "obligatory genes"), and up to 1300 "facultative" genes that vary from strain to strain and from species to species. In closely related species, obligatory and facultative genes are orthologous genes that are found at similar loci. We have analyzed a set of facultative genes involved in the degradation of the carbohydrates galactitol, D-tagatose, D-galactosamine and N-acetyl-galactosamine in various pathogenic and non-pathogenic strains of these bacteria. The four carbohydrates are transported into the cell by phosphotransferase (PTS) uptake systems, and are metabolized by closely related or even identical catabolic enzymes via pathways that share several intermediates. In about 60% of Escherichia coli strains the genes for galactitol degradation map to a gat operon at 46.8 min. In strains of Salmonella enterica, Klebsiella pneumoniae and K. oxytoca, the corresponding gat genes, although orthologous to their E. coli counterparts, are found at 70.7 min, clustered in a regulon together with three tag genes for the degradation of D-tagatose, an isomer of D-fructose. In contrast, in all the E. coli strains tested, this chromosomal site was found to be occupied by an aga/kba gene cluster for the degradation of D-galactosamine and N-acetyl-galactosamine. The aga/kba and the tag genes were paralogous either to the gat cluster or to the fru genes for degradation of D-fructose. Finally, in more then 90% of strains of both Klebsiella species, and in about 5% of the E. coli strains, two operons were found at 46.8 min that comprise paralogous genes for catabolism of the isomers D-arabinitol (genes atl or dal) and ribitol (genes rtl or rbt). In these strains gat genes were invariably absent from this location, and they were totally absent in S. enterica. These results strongly indicate that these various gene clusters and metabolic pathways have been subject to convergent evolution among the Enterobacteriaceae. This apparently involved recent horizontal gene transfer and recombination events, as indicated by major chromosomal rearrangements found in their immediate vicinity.

Acetylgalactosamine↗
PubMed2003

Irinotecan plus raltitrexed vs raltitrexed alone in patients with gemcitabine-pretreated advanced pancreatic adenocarcinoma.

There is no established second-line treatment for advanced pancreatic cancer after gemcitabine failure. In view of the urgent need for such therapy, and since preclinical and phase I clinical data suggest an encouraging, potentially synergistic activity between raltitrexed and irinotecan, the present randomised phase II study was initiated. A total of 38 patients with metastatic pancreatic adenocarcinoma, who progressed while receiving or within 6 months after discontinuation of palliative first-line chemotherapy with gemcitabine, were enrolled in this study. They were randomised to 3-weekly courses of raltitrexed 3 mg x m(-2) on day 1 (arm A) or irinotecan 200 mg x m(-2) on day 1 plus raltitrexed 3 mg x m(-2) on day 2 (arm B). The primary study end point was objective response, secondary end points included progression-free survival (PFS) and overall survival (OS), as well as clinical benefit response in symptomatic patients (n=28). In the combination arm, the IRC-confirmed objective response rate was 16% (three out of 19 patients had a partial remission; 95% CI, 3-40%), which was clearly superior to that in the comparator/control arm with raltitrexed alone, in which no response was obtained. Therefore, the trial was already stopped at the first stage of accrual. Also, the secondary study end points, median PFS (2.5 vs 4.0 months), OS (4.3 vs 6.5 months), and clinical benefit response (8 vs 29%) were superior in the combination arm. The objective and subjective benefits of raltitrexed+irinotecan were not negated by severe, clinically relevant treatment-related toxicities: gastrointestinal symptoms (42 vs 68%), partial alopecia (0 vs 42%), and cholinergic syndrome (0 vs 21%) were more commonly noted in arm B; however, grade 3 adverse events occurred in only three patients in both treatment groups. Our data indicate that combined raltitrexed+irinotecan seems to be an effective salvage regimen in patients with gemcitabine-pretreated pancreatic cancer. The superior response activity, PFS and OS (when compared to raltitrexed), as well as its tolerability and ease of administration suggest that future trials with this combination are warranted.

Adenocarcinoma↗
PubMed2003

[Occupationally acquired tuberculosis in an administrative assistant: aspects of an expert report].

HISTORY: Since the age of 48 years an administrative assistant had been treated with immunosuppressive drugs for a mixed connective tissue disease. She was in direct personal contact with newly arrived Africans while working at an admittance centre for refugees. At the age of 53 years the symptoms changed with increasing joint pains and loss of weight. The immunosuppressive therapy with corticoids was increased. A total hip arthroplasty followed. An infection of the wound occurred and many revisions of the scar tissue followed. After a total knee arthroplasty an epileptic seizure occurred. A tuberculous meningoencephalitis was diagnosed. Mycobacterium tuberculosis was detected in urine, sputum and in secretions of different joints. A detailed analysis revealed Mycobacterium tuberculosis var. africanum. At the age of 59 years the patient died during a period of rehabilitation, the clinical signs indicating pulmonary embolism. CONCLUSIONS: The haematogenous spread of Mycobacterium tuberculosis was undoubtedly exacerbated by the immunosuppressive therapy. As a preventive measure a competent occupational consultation could have stopped the occupational exposure to Mycobacteria by transferring the patient during immunosuppressive therapy. The change of symptoms had been misclassified as worsening of the mixed connective tissue disease. Considering legal aspects of the German social insurance system the criteria of an occupational disease would have been fulfilled.

Adrenal Cortex Hormones↗
PubMed2003

Biweekly high-dose gemcitabine alone or in combination with capecitabine in patients with metastatic pancreatic adenocarcinoma: a randomized phase II trial.

BACKGROUND: Gemcitabine is an active antitumor agent in the treatment of advanced pancreatic cancer, and has shown potential synergistic activity with the oral fluoropyrimidine capecitabine in previous phase I/II trials. Based on this background and in order to define the therapeutic potential and tolerance of this combination more precisely, the present randomized multicenter phase II trial was initiated. PATIENTS AND METHODS: We prospectively randomized 83 patients to treatment with biweekly gemcitabine 2,200 mg/m(2) given as a 30 min intravenous infusion on day 1, or the same treatment plus oral capecitabine 2,500 mg/m(2) given from days 1 to 7. In both arms, chemotherapy was administered for a duration of 6 months unless there was prior evidence of progressive disease. The efficacy of the two treatment arms was evaluated according to standard criteria, i.e. objective response, progression-free survival (PFS) and overall survival (OS), as well as by analysis of clinical benefit response. RESULTS: The overall objective response rate among the 42 patients treated with gemcitabine alone was 14% compared with 7/41 (17%) among those treated with the combination arm. Similar to response rates, there was no apparent difference between the two groups in terms of median PFS (4.0 versus 5.1 months) and median OS (8.2 versus 9.5 months) in the gemcitabine and combination arm, respectively. Of 61 patients with tumor-related symptoms, who were considered evaluable for clinical benefit response, 10/30 (33%) and 15/31 (48.4%) experienced significant palliation in the gemcitabine and combination arm, respectively. Chemotherapy was well tolerated in both arms with only four versus six patients experiencing WHO grade 3 symptoms. Apart from the occurrence of hand-foot syndrome in 10 patients, no major increase in incidence and/or degree of adverse reactions was noted in the combination arm. CONCLUSIONS: Results of this trial suggest a fairly good therapeutic index for the combination of biweekly high-dose gemcitabine and capecitabine for the treatment of advanced pancreatic cancer. Despite a somewhat superior clinical benefit response rate, no advantage over single-agent gemcitabine, however, was noted in terms of objective efficacy parameters.

Adenocarcinoma↗
PubMed2002

Site-directed mutagenesis within the central constriction site of ScrY (sucroseporin): effect on ion transport and comparison of maltooligosaccharide binding to LamB of Escherichia coli.

The 3-D structures of the maltooligosaccharide-specific LamB-channel of Escherichia coli (also called maltoporin) and sucrose-specific ScrY (sucroseporin) are known from X-ray crystallography. The central constriction of the channels formed by the external loop 3 is controlled by a number of different amino acids. The most prominent one of these, N192, D201 and F204, were replaced by site-directed mutagenesis into those of LamB, which, according to the 3-D model of both channels are localized at similar places. The ScrY single mutants ScrYN192R, ScrYD201Y and ScrYF204D and the ScrY triple mutant ScrY3113 (N192R + D201Y + F204D) were created together with the triple mutant ScrY3213, which lacks also amino acids 1 to 61 from the N-terminal end. The mutant proteins were purified to homogeneity and were reconstituted into lipid bilayer membranes. In these experiments, the single-channel conductance of the mutants in different salt solutions and the stability constants for binding of different maltooligosaccharides to the mutant channels was measured using titration experiments with carbohydrates. The carbohydrate-induced block of the channel function could also be used for the study of current noise through the different mutant ScrY-channels. The analysis of the power density spectra allowed the evaluation of the on- and off-rate constants (k1 and k-1) of carbohydrate-binding to the binding site inside the channels. The results suggest that both on- and off-rate constants were affected by the mutations. Most of them showed a substantial effect on carbohydrate binding kinetics. Nevertheless, single-channel conductance and carbohydrate binding of ScrY3113 mutant were still different from that of LamB, suggesting that not only the amino acids of the central constriction but also the general architecture of both channels have a substantial influence on channel properties.

Bacterial Outer Membrane Proteins↗
PubMed2002

A case of lung transplantation following Mycoplasma pneumoniae infection.

Reported here is a case of severe necrotizing pneumonia following Mycoplasma pneumoniae infection that occurred in a 55-year-old man. The histological changes of lung parenchyma included granulomas and bronchiolitis obliterans. Mycoplasma infection was diagnosed by repeated antibody determination (complement fixation test) and confirmed using the polymerase chain reaction to detect the pathogen from a tracheal aspirate. Prior to this episode of pneumonia, the patient had been healthy, except for Reiter's disease that had been diagnosed 18 years previously. In addition to severe pulmonary involvement, the patient developed rhabdomyolysis with subsequent acute renal failure, Stevens-Johnson syndrome, biochemical pancreatitis, severe anemia, and an effusion of the right knee. Contrary to the symptoms of pulmonary disease, all of the extrapulmonary manifestations except anemia were transient. Due to persistent respiratory insufficiency and long-term failure to wean the patient from a respirator, a lung transplantation was performed. Five weeks after transplantation the patient died as a result of intrapulmonary hemorrhage. To the best of our knowledge, this is the first report of pneumonia due to Mycoplasma pneumoniae leading to lung transplantation. Furthermore, the multiple extrapulmonary manifestations in this case make it exceptional.

Anti-Bacterial Agents↗