Environmental factors shaping the gut microbiome in a Dutch population.

The gut microbiome is associated with diverse diseases1-3, but a universal signature of a healthy or unhealthy microbiome has not been identified, and there is a need to understand how genetics, exposome, lifestyle and diet shape the microbiome in health and disease. Here we profiled bacterial composition, function, antibiotic resistance and virulence factors in the gut microbiomes of 8,208 Dutch individuals from a three-generational cohort comprising 2,756 families. We correlated these to 241 host and environmental factors, including physical and mental health, use of medication, diet, socioeconomic factors and childhood and current exposome. We identify that the microbiome is shaped primarily by the environment and cohabitation. Only around 6.6% of taxa are heritable, whereas the variance of around 48.6% of taxa is significantly explained by cohabitation. By identifying 2,856 associations between the microbiome and health, we find that seemingly unrelated diseases share a common microbiome signature that is independent of comorbidities. Furthermore, we identify 7,519 associations between microbiome features and diet, socioeconomics and early life and current exposome, with numerous early-life and current factors being significantly associated with microbiome function and composition. Overall, this study provides a comprehensive overview of gut microbiome and the underlying impact of heritability and exposures that will facilitate future development of microbiome-targeted therapies.

Enhanced photocatalytic activity, transport properties and electronic structure of Mn doped GdFeO3 synthesized using the sol-gel process.

In this work we have synthesized Mn doped GdFeO3 nano-particles using a green and facile sol gel method and studied their photocatalytic, optical, vibrational and electrical properties. The Rietveld refinement of the XRD profiles suggests that all the materials have an orthorhombic Pbnm crystal structure. The transmission electron microscope (TEM) images show the decrease of the average particle size from 140 to 80 nm with the Mn concentration. The high crystallinity of the synthesized particles is confirmed from the HR-TEM images. Raman spectrum is employed to investigate the phonon modes of the materials. The optical band gap of the materials is obtained from the UV-vis reflectance spectroscopy (DRS) using Tauc relation which indicates the reduction of the band gap from 2.18 to 1.72 eV with Mn-doping. The photocatalytic activity of the materials is studied by the photocatalytic degradation of rhodamine B (Rh-B) in aqueous solution under visible light illumination. The substitution of Mn at the Fe site introduces an extra electronic state between the conduction band and the valence band which reduces the electronic band gap and enhances the Rh-B degradation efficiency. A 30% Mn doping at the Fe site (GFMO3) provides an optimum space charge width which assists to attain the maximum rate of degradation of the Rh-B dye. The doping of Mn3+ reduces the photogenerated electron and hole recombination rate and hence more charge carriers take part in the redox reaction which facilitates the photo-catalytic efficiency in GFMO3. The degradation rate enhances by a factor of 2.5 for GFMO3 as compared to pure GdFeO3. The highest photocurrent density of 1.31 µA cm-2 of GFMO3 with respect to other materials promotes the separation and transfer of the photo generated charge carriers. The possible photocatalytic mechanism of the Mn doped GdFeO3 is also critically discussed. Alternating current impedance spectroscopy is used to study the electrical properties of the synthesized materials. The increase in the conductivity with the Mn concentration is explained on the basis of the band gap reduction and this is consistent with the Smit and Wijn theory. Magnetic measurement is performed to measure the magnetization strength which is useful to separate the photocatalyst by simply using a magnet. The temperature dependent magnetization measurement suggests the anti-ferromagnetic (AFM) behaviour of the studied materials with the decrease of Néel temperature (TN) with Mn concentration. The XPS study reveals the presence of multiple oxidation states of Fe(2+/3+) and Mn(4+/3+) in these materials which facilitates the conductivity as well as the oxidation/reduction efficiency at the surface of the catalyst. The band gap reduction and its effect on the enhancement of the photocatalytic degradation efficiency with Mn doping are also discussed from the density of states calculations. Thus, this study describes a promising approach for the organic pollutant degradation by designing an efficient and stable perovskite photocatalyst.

Gut feelings: the relations between depression, anxiety, psychotropic drugs and the gut microbiome.

The gut microbiome is involved in the bi-directional relationship of the gut - brain axis. As most studies of this relationship are small and do not account for use of psychotropic drugs (PTDs), we explored the relations of the gut microbiome with several internalizing disorders, while adjusting for PTDs and other relevant medications, in 7,656 Lifelines participants from the Northern Netherlands (5,522 controls and 491 participants with at least one internalizing disorder). Disorders included dysthymia, major depressive disorder (MDD), any depressive disorder (AnyDep: dysthymia or MDD), generalized anxiety disorder (GAD) and any anxiety disorder (AnyAnx: GAD, social phobia and panic disorder). Compared to controls, 17 species were associated with depressive disorders and 3 were associated with anxiety disorders. Around 90% of these associations remained significant (FDR <0.05) after adjustment for PTD use, suggesting that the disorders, not PTD use, drove these associations. Negative associations were observed for the butyrate-producing bacteria Ruminococcus bromii in participants with AnyDep and for Bifidobacterium bifidum in AnyAnx participants, along with many others. Tryptophan and glutamate synthesis modules and the 3,4-Dihydroxyphenylacetic acid synthesis module (related to dopamine metabolism) were negatively associated with MDD and/or dysthymia. After additional adjustment for functional gastrointestinal disorders and irritable bowel syndrome, these relations remained either statistically (FDR <0.05) or nominally (P < 0.05) significant. Overall, multiple bacterial species and functional modules were associated with internalizing disorders, including gut - brain relevant components, while associations to PTD use were moderate. These findings suggest that internalizing disorders rather than PTDs are associated with gut microbiome differences relative to controls.

Electron spin resonance for detecting polyadenylate tracts in RNA's.

Electron spin resonance is used to detect RNA's that contain polyadenylate tracts. The method depends on the ability of RNA's that contain polyadenylate sequences to associate with poly(2'-deoxy-2'-fluoro)uridylic acid, which has been spin-labeled with 4-(2-iodoacetamido)-2,2,6,6-tetramethylpiperidinooxyl. The formation of the hybridization product can be detected by monitoring the decrease in mobility of the spin probe.

Infrared tunable, two colour-band photodetectors on flexible platforms using 0D/2D PbS-MoS2 hybrids.

Two-dimensional (2D) MoS2 nanosheets have been integrated with zero-dimensional (0D) PbS quantum dots to achieve a superior optical response extending to the short-wavelength infrared region along with a broadband visible response for multispectral photodetection. The 0D/2D hybrid nanostructures have been synthesized by a one pot, stabilizer-free solvothermal growth process. Microscopic and spectroscopic studies confirmed the formation of PbS QD decorated semiconducting 2H-MoS2 layers. The size tunable absorption features with longer photo-generated carrier lifetime of synthesized hybrid nanostructures indicate that the integration of PbS QDs in MoS2 could be a viable approach for fabricating two-colour band photodetectors, viz. visible broadband and wavelength selective short-wave IR photodetectors. Devices have also been demonstrated on polyethylene terephthalate substrates using a solution-based synthesis technique for flexible and ultrathin optoelectronic device applications. The photodetection performance of fabricated devices suggests that the synergic 0D/2D hybrid nanostructures are significantly superior to solution processed hybrid devices operating in the infrared region. The successful integration of 0D QDs in 2D materials may pave the way for novel, high performance, next-generation CMOS compatible flexible photonic devices.

Development and clinical application of a new method for the radioimmunoassay of arginine vasopressin in human plasma.

A radioimmunoassay has been developed that permits reliable measurements of plasma arginine vasopressin (AVP) at concentrations as low as 0.5 pg/ml in sample volumes of 1 ml or less. Nonhormonal immunoreactivity associated with the plasma proteins is eliminated by acetone precipitation before assay, leaving unaltered a component that is immunologically and chromatographically indistinguishable from standard AVP. Storage of plasma results in a decline in AVP concentration and, thus, must be carefully regulated. The plasma AVP values obtained by our method approximate the anticipated levels and vary in accordance with physiologic expections. In recumbent normal subjects, plasma AVP ranged from (mean +/-SD) 5.4+/-3.4 pg/ml after fluid deprivation to 1.4+/-0.8 pg/ml after water loading, and correlated significantly with both plasma osmolality (r=0.52; P<0.001) and urine osmolality (r=0.77; P<0.001). After fluid restriction, plasma AVP was uniformly normal relative to plasma osmolality in patients with nephrogenic diabetes insipidus and primary polydipsia but was distinctly subnormal in all patients with pituitary diabetes insipidus. The infusion of physiologic amounts of posterior pituitary extract caused a dose-related rise in plasma vasopressin that afterwards declined at the expected rate (t(1/2)=22.5+/-4 min). We conclude that, when used appropriately, our radioimmunoassay method provides a useful way of assessing AVP function in man.

Evidence that increased circulating 1 alpha, 25-dihydroxyvitamin D is the probable cause for abnormal calcium metabolism in sarcoidosis.

Mean plasma 1(alpha),25-dihydroxyvitamin D[1(alpha),25(OH)(2)D] was significantly increased and serum parathyroid hormone was suppressed in three patients with sarcoidosis and hypercalcemia. Prednisone lowered the mean plasma 1(alpha),25(OH)(2)D to normal range and corrected the hypercalcemia. To elucidate the mechanism for the increased sensitivity to vitamin D in this disorder, the effects of orally-administered vitamin D(2) were determined in seven normal subjects, four patients with sarcoidosis and normal calcium metabolism and three patients with sarcoidosis and a history of hypercalcemia who were normocalcemic when studied. Serum and urinary calcium, serum 25-hydroxyvitamin D (25-OHD), plasma 1(alpha),25(OH)(2)D and, in some studies, calcium balance were measured. Vitamin D(2), 250 mug a day for 12 d, produced little, if any, change in mean plasma 1(alpha),25(OH)(2)D and in urinary calcium in the normals and in the patients with normal calcium metabolism. In contrast, vitamin D(2) produced increases in plasma 1(alpha),25(OH)(2)D from concentrations which were within the normal range (20-55 pg/ml) to abnormal values and increased urinary calcium in two patients with abnormal calcium metabolism. In an abbreviated study in the third patient, vitamin D(2), 250 mug a day for 4 d, also increased plasma 1(alpha),25(OH)(2)D abnormally from a normal value. There was a highly significant correlation between plasma 1(alpha),25(OH)(2)D and urinary calcium. Serum 25-OHD and serum calcium remained within the normal range in all subjects and patients. These findings provide evidence that the defect in calcium metabolism in sarcoidosis probably results from impaired regulation of the production and(or) degradation of 1(alpha),25(OH)(2)D. Prednisone may act to correct the abnormal calcium metabolism by reducing circulating 1(alpha),25(OH)(2)D.

Effects of dibutyryl cyclic adenosine 3',5'-monophosphate and parathyroid extract on calcium and phosphorus metabolism in hypoparathyroidism and pseudohypoparathyroidism.

It has been proposed previously that the metabolic defect in pseudohypoparathyroidism which accounts for parathyroid hormone unresponsiveness is an absence or abnormal form of the adenyl cyclase system in kidney and presumably in bone. To determine whether there is an associated defect in the response mechanism to cyclic adenosine 3',5'-monophosphate (cyclic AMP), the effects of parathyroid extract (PTE), and dibutyryl cyclic AMP were compared in patients with either surgical hypoparathyroidism or pseudohypoparathyroidism. PTE and dibutyryl cyclic AMP both increased serum and urinary calcium, lowered the serum phosphorus, and increased urinary phosphorus in patients with hypoparathyroidism. PTE also increased urinary cyclic AMP in these patients. PTE increased serum and urinary calcium and urinary phosphorus but did not alter serum phosphorus or urinary cyclic AMP in the patients with pseudohypoparathyroidism. Dibutyryl cyclic AMP increased the serum and urinary calcium, lowered the serum phosphorus, and increased urinary phosphorus in all the patients with pseudohypoparathyroidism. The results indicate that (a) dibutyryl cyclic AMP can reproduce the effects of parathyroid hormone on calcium and phosphorus metabolism in man, (b) the response mechanism to cyclic AMP appears to be intact in pseudohypoparathyroidism, and (c) PTE apparently produces some of its characteristic effects on calcium and phosphorus metabolism in pseudohypoparathyroidism in the absence of an increase in urinary cyclic AMP.

A prototype ultrasound-guided laparoscopic radiofrequency ablation system.

BACKGROUND: Advanced laparoscopic procedures, particularly laparoscopic liver resection and ablation, may benefit from image-guided surgery techniques that involve interactive three-dimensional imaging and instrument tracking. METHODS: A prototype system for laparoscopic ultrasound-guided radiofrequency ablation was designed and implemented. This system uses an infrared camera to track instruments and runs on a personal computer. Features of the system include spatially registered ultrasound visualization, volume reconstruction, and interactive targeting. Targeting of accuracy studies was performed by directing a tracked needle to a phantom target. RESULTS: Ultrasound data collection and volume reconstruction can be achieved within minutes and interactively reviewed by the surgeon. Early results with phantom experiments demonstrate a targeting accuracy of 5 to 10 mm. CONCLUSIONS: These results support the further development of this and similar image-guided surgery systems for specific laparoscopic procedures. Eventually, rigorous clinical evaluation will be necessary to prove their value.

Renal Transplantation - An Experience of 500 Patients.

BACKGROUND: Renal transplantation is the treatment modality of choice for patients with end stage kidney failure. We present our experience of graft and patient survival of initial 500 renal transplants performed between May 1991 and July 2006, at Army Hospital (R&R). MATERIAL AND METHODS: All patients received triple drug immunosuppression with cyclosporine/tacrolimus, azathioprine/ mycophenolate mofetil and steroids. Patients in high risk group received induction therapy with IL-2 receptor blockers/anti-thymocyte globulin. RESULTS: Majority of the recipients (79%) were males, whereas majority of the donors (59.4%) were females. In the donor profile, 385 (77%) transplants were live related, 108 (21.6 %) were spousal and 7 (1.4%) were cadaveric transplants. Mean age of the donors and recipients was 42.11 ± 11.53 years (range 19-72 years) and 33 ± 9.39 years (range 5-60 years) respectively. Eighty two patients (16.4%) were lost to follow up and the present data on rejections, patients and graft survival pertains to 418 patients. These patients have been followed up for a mean period of 2.63 years (SE, 0.122; median 1.8 years; range 0-13.36 years). Acute rejection episodes occurred in 115 (27.3%) patients and 95% of these could be reversed with steroids/ATG. Sixty eight patients (16%) have died on follow-up. Our one-year, 5 year and 10 year estimated graft survival is 95.4% (SE, 0.01), 80.5% (SE, 0.03) and 53.1% (SE, 0.09) respectively and patient survival at one year is 93.2% (SE, 0.01). The estimated graft and patient survival in our series is 9.83 (95% CI, 8.92-10.73) and 9.80 (8.93-10.67) years respectively. CONCLUSION: This centre's short-term graft survival of 95.4% is comparable to the best centres of the world.

Synergistic effect of polymer encapsulated silver nanoparticle doped WS2 sheets for plasmon enhanced 2D/3D heterojunction photodetectors.

Chemical doping and plasmonic enhanced photoresponsivity of two dimensional (2D) n-WS2/p-Si heterojunctions are demonstrated for the first time. Novel PVP coated Ag0 intercalation induced synthesis has led to the formation of impurity-free, chemically doped few-layer n-WS2 with reversed conductivity following the Maxwell-Wagner-Sillars interfacial effect. The resultant composite film exhibits excellent stability and tunable plasmonic absorption due to silver nanoparticles of different sizes. A sharp band-edge absorption of the hybrid material indicates the presence of spin-orbit coupled direct band gap transitions in WS2 layers, in addition to a broader plasmonic peak attributed to Ag nanoparticles. Stabilized Ag-nanoparticle (∼4-6 nm) embedded electron rich n-WS2 has been used to fabricate plasmon enhanced, silicon compatible heterojunction photodetectors. The detectors exhibited superior properties, possessing a photo-to-dark current ratio of ∼103, a very high responsivity (8.0 A W-1) and an EQE of 2000% under 10 V bias with a broad spectral photoresponse in the wavelength range of 400-1100 nm. The results provide a new paradigm for intercalant impurity-free metal nanoparticle assisted exfoliation of n-type few-layer WS2, with the nanoparticles playing a dual role towards the realization of 2D materials based broadband heterojunction optoelectronic devices by inducing chemical doping as well as tunable plasmon enhanced absorption.

A Comparative Study of Laparoscopic with Conventional Open Donor Nephrectomy in Renal Transplantation.

BACKGROUND: Laparoscopic donor nephrectomy (LDN) has been gaining popularity among kidney donors. There have been concerns about the safety and efficacy of the procedure as compared to open donor nephrectomy (ODN). We compare our results on LDN with ODN. METHODS: We retrospectively analysed our data of LDN and ODN. Duration of surgery, blood loss, period of hospitalisation, per oral intake and analgesic requirements. RESULT: 22 LDNs were done, the operation time ranged from 220-300 minutes, and blood loss from 100-150ml. In the first 10 laparoscopic operations four cases required conversion to open surgical dissection. Only one case was converted to open surgery in the subsequent 12 laparoscopic cases. Oral intake was started on the first postoperative day. Analgesic requirement in laparoscopy cases was less. Patients were mobilised on the first day after surgery. Patients were discharged by seventh day. There was no significant difference in the functioning of the graft after revascularisation in the recipient. CONCLUSION: Laparoscopic donor nephrectomy is a safe and effective technique of donor nephrectomy.

Nucleic acid interaction with VERO cells. A temperature barrier in the interaction pattern.

The interaction of VERO cell monolayers with spin (nitroxide)-(labeled polynucleotides (1(N)n) was examined by electron spin resonance (ESR) spectroscopy at various temperatures. Nitroxide labels covalently linked to (A)n, (dUfl)n, (U)n and (A)n . (U)n were used to monitor the interaction. The VERO cells were grown on small quartz plates with a cell viability of 95% or better and then used directly for the ESR studies. The ESR results indicated that the interaction between VERO cells and spin-labeled nucleic acids is temperature dependent. No temperature dependence was found when VERO cells were in contact with nitroxide radicals which were free in solution or covalently bound to Sepharose 4B. The temperature dependence established with nitroxide-labeled nucleic acids indicates that a temperature barrier must exist between 20 and 26 degrees C for the interaction between nucleic acids and VERO cells; namely, at 26 degrees C or above spin-labeled nucleic acids interact significantly with a VERO cell surface; whereas, at 20 degrees C the ESR signal reports no interaction. It is concluded that a temperature-dependent phase transition of membrane components or cell surface products active at 26 degrees C or above play a key role in the nucleic acid cell surface interaction process.

Dielectric Relaxation of NiFe2O4/Gd2O3 Core-Shell Nanoparticles.

Gd2O3 encapsulated NiFe2O4 core-shell nano-particles (CSNPs) have been synthesized by chemical route. The phase formation of the materials is confirmed by X-ray diffraction analysis. The average particle size is found to be 60 nm by transmission electron microscope. The band gap of NiFe2O4/Gd2O3 CSNPs is obtained by UV-visible absorption spectroscopy. The observed band gap of 4.38 eV lies in between the individual band gap of Gd2O3 and NiFe2O4. The frequency-dependent dielectric relaxation of the material is investigated in the temperature range from 303 K to 543 K. The temperature dependent relaxation times are found to obey Arrhenius law having activation energy of 0.3 eV. The Nyquist plots of impedance data are analyzed by the RC equivalent circuit having a constant phase element. The dielectric relaxation is modelled by Havriliak-Negami technique in the electric modulus formalism. The frequency dependent conductivity spectra follow the double power law.

Demonstration of a diurnal variation in serum parathyroid hormone in primary and secondary hyperparathyroidism.

It had been reported previously that there is a diurnal variation in serum parathyroid hormone (PTH) in normal subjects but not in patients with primary hyperparathyroidism. Studies were performed to determine whether there is a diurnal variation in serum PTH in primary or secondary hyperparathyroidism and whether the nocturnal increase in serum PTH, if present, could be prevented by induced hypercalcemia. Serum PTH and calcium were measured in five normal subjects, two patients with pseudohypoparathyroidism, and fourteen patients with primary hyperparathyroidism, twelve of whom were subsequently found to have parathyroid adenomas. In the normals, there was a mean decline in serum PTH of 0.07 ng/ml before noon and a mean increase of 0.04 ng/ml after 8 PM. In primary hyperparathyroidism there was a mean decline in serum PTH before noon of 0.11 ng/ml and a mean increase of 0.11 ng/ml after 8 PM. In both groups, the lowest mean serum calcium values were noted between midnight and 6:00 AM. Patients with pseudohypoparathyroidism showed a nocturnal increase in serum PTH. In each of two normal subjects, two patients with primary hyperparathyroidism, and two patients with pseudohypoparathyroidism, calcium, 4 mg/kg body weight per hour for 4 hours (8:00 PM to 12 midnight), produced hypercalcemia and prevented the nocturnal increase in serum PTH. We have concluded that a diurnal variation in serum PTH often occurs in both normal subjects and in patients with primary or secondary hyperparathyroidism and that nocturnal increases in serum PTH can be prevented by induced hypercalcemia.

Relationship between latitude and melanoma incidence: international evidence.

We investigate the relationship between latitude and incidence of melanoma among Whites in different age groups using data from different continents. Relevant data for Whites were obtained for 59 regions around the world. A statistical analysis was carried out using regional dummy variables to eliminate spurious statistical correlation due to clustering. Simple correlation between latitude and incidence of melanoma is strongly negative for almost all age groups. However, once the regional dummies were introduced in the analysis, the relation between latitude and incidence rates disappeared for all age groups but the explanatory power of the regression equation increased substantially.

Cytologic screening for the detection of cancer in the uterine cervix--a survey in Patna (India).

Cytologic screening of the uterine cervix of 10,012 married women of Patna (India) was conducted to find out precancerous and cancerous lesions in different age and parity groups. Of the "pap" smears, 80.1% were normal, 11.1% were inflammatory, 5.8% showed dyskaryosis and 2.8% had cellular profiles suggestive of malignancy. In higher age groups i.e., in 40-49 and 50-59 years, the percentage of inflammatory smears were increased to 15 and 35.8; and invasive carcinoma to 8.28 and 14.19, respectively. Higher parity groups (four and above) had greater incidence of invasive carcinoma (6.7%) than those of lower parity groups (1.88%).

Biosoluble surgical material from 2,3-dialdehyde cellulose.

Dialdehyde cellulose (DAC) was prepared by periodate oxidation of various cellulosic materials in the form of sutures and bandages. The suitability of using DAC for making bioabsorbable sutures and antimicrobial wound dressing bandages was studied. The investigations indicated that DAC combines the requisite mechanical strength with an inherent antimicrobial nature. It was found that the oxidation of cellulose to yield DAC also rendered it bioabsorbable. The DAC was coated with different concentrations of urea formaldehyde in order to improve the mechanical properties for making sutures.

On the lipolytic action of parathyroid hormone in man.

An investigation was carried out to determine whether bovine PTH stimulates lipolysis in human fat tissue, whether this action is mediated by cyclic adenosine 3', 5'-monophosphate and whether the N-terminal 1-34 peptide of bovine PTH is responsible for the lipolytic effect. Studies were also performed to determine if parathyroid extract (PTE) produces lipolysis in normal subjects and in patients with pseudohypoparathyroidism in whom there is a defect in the adenylate system in response to PTH in the renal cortex and presumably in the skeletal system as well. It was found that highly purified bovine PTH in the concentration range between 10(-9) M and 10(-5) M stimulated lipolysis in vitro by human fat in a dose-dependent manner. Significant increases in glycerol production were observed at concentrations of PTH as low as 10(-9) M and maximal increases were seen at 10(-6) M. The hormone significantly increased the concentration of cyclic adenosine 3' ,5'-monophosphate in fat tissue. The synthetic N-terminal 1-34 peptide of bovine PTH was as effective as the native hormone in stimulating glycerol production at a concentration of 10(-9) M-10(-6) M. PTE, 100 mU per kg per min for 30 min given intravenously, produced transient increases in the concentration of plasma free fatty acid in each of eight normal subjects, three patients with hypoparathyroidism and eight patients with pseudohypoparathyroidism. Purified bovine PTH also increased plasma free fatty acid in each of two normal subjects. It is concluded that PTH stimulates lipolysis in human subcutaneous fat, that this action of the hormone is mediated through cyclic adenosine 3', 5'-monophosphate and that the N-terminal 1-34 peptide portion of the hormone is responsible for this lipolytic action. Further, PTE stimulates lipolysis in vivo in man. There appears to be no defect in the adenylate cyclase system in the fat cell in response to PTH in patients with pseudohypoparathyroidism.

The joint contributions of saccades and ocular drift to repeated ocular fixations.

We measured the joint contributions of different sized saccades and ocular drift to overall performance in an alternating fixation task. Subjects repeatedly shifted fixation between the centres of a pair of bars of width 2 degrees -2 arc min, either mentally selected or electronically cut from a stationary sine grating display. Eye movement patterns exhibited consistent features across all displays, and pairs of widely separated bars were studied most. Variability (S.D.) and relative accuracy (under/overshooting bias) were estimated from the concentration of eye positions over the two target bars. Overall variability, i.e. for eye movements as a whole, reached a minimum of 5 min for bar widths less than 20 min across subjects, displays and tasks. This was consistent, as were several other aspects of the study, with a constant 20-min diameter goal zone hypothesis. For wide bars, overall variability increased nearly as the square root of bar width, and for narrow bars, was independent of bar separation. A typical between-bar crossing saccade was tightly constrained in departure point but widely scattered in landing position, the associated variability increasing with bar separation. The final high overall precision was achieved largely by within-bar saccades of greater than 7.5 min effective amplitude that were present at a rate of 1 (range 0.3-3) per crossing saccade. This is consistent with views that very small saccades (the smaller microsaccades) make little obvious contribution to oculomotor performance.