Andrew J M Boulton

Central Manchester University Hospitals NHS Foundation Trust, Manchester, England, United Kingdom

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Publications (495)2334.44 Total impact

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    ABSTRACT: Objective: Muscle weakness and atrophy of the lower limbs may develop in patients with diabetes, increasing their risk of falls. The underlying basis of these abnormalities has not been fully explained. The aim of this study was to objectively quantify muscle strength and size in patients with type 2 diabetes mellitus (T2DM) in relation to the severity of neuropathy, intramuscular noncontractile tissue (IMNCT), and vitamin D deficiency. Research design and methods: Twenty patients with T2DM and 20 healthy control subjects were matched by age, sex, and BMI. Strength and size of knee extensor, flexor, and ankle plantar and dorsiflexor muscles were assessed in relation to the severity of diabetic sensorimotor polyneuropathy (DSPN), amount of IMNCT, and serum 25-hydroxy vitamin D (25OHD) levels. Results: Compared with control subjects, patients with T2DM had significantly reduced knee extensor strength (P = 0.003) and reduced muscle volume of both knee extensors (P = 0.045) and flexors (P = 0.019). Ankle plantar flexor strength was also significantly reduced (P = 0.001) but without a reduction in ankle plantar flexor (P = 0.23) and dorsiflexor (P = 0.45) muscle volumes. IMNCT was significantly increased in the ankle plantar (P = 0.006) and dorsiflexors (P = 0.005). Patients with DSPN had significantly less knee extensor strength than those without (P = 0.02) but showed no difference in knee extensor volume (P = 0.38) and ankle plantar flexor strength (P = 0.21) or volume (P = 0.96). In patients with <25 nmol/L versus >25 nmol/L 25OHD, no significant differences were found for knee extensor strength and volume (P = 0.32 vs. 0.18) and ankle plantar flexors (P = 0.58 vs. 0.12). Conclusions: Patients with T2DM have a significant reduction in proximal and distal leg muscle strength and a proximal but not distal reduction in muscle volume possibly due to greater intramuscular fat accumulation in distal muscles. Proximal but not distal muscle strength is related to the severity of peripheral neuropathy but not IMNCT or 25OHD level.
    Full-text · Article · Jan 2016 · Diabetes care
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    Preview · Article · Jan 2016 · Diabetes Care
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    Full-text · Article · Oct 2015 · Journal of diabetes science and technology
  • K Markakis · F L Bowling · A J M Boulton
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    ABSTRACT: In 2015, it can be said that the diabetic foot is no longer the Cinderella of diabetic complications. Thirty years ago there was little evidence-based research taking place on the diabetic foot, and there were no international meetings addressing this topic. Since then, the biennial Malvern Diabetic Foot meetings started in 1986, the American Diabetes Association founded their Foot Council in 1987, and the European Association for the Study of Diabetes established a Foot Study Group in 1998. The first International Symposium on the Diabetic Foot in the Netherlands was convened in 1991, and this was soon followed by the establishment of the International Working Group on the Diabetic Foot that has produced useful guidelines in several areas of investigation and the management of diabetic foot problems. There has been an exponential rise in publications on diabetic foot problems in high impact factor journals, and a comprehensive evidence-base now exists for many areas of treatment. Despite the extensive evidence available, it, unfortunately, remains difficult to demonstrate that most types of education are efficient in reducing the incidence of foot ulcers. However, there is evidence that education as part of a multi-disciplinary approach to diabetic foot ulceration plays a pivotal role in incidence reduction. With respect to treatment, strong evidence exists that offloading is the best modality for healing plantar neuropathic foot ulcers, and there is also evidence from 2 randomized controlled trials to support the use of negative-pressure wound therapy in complex post-surgical diabetic foot wounds. Hyperbaric oxygen therapy exhibits the same evidence level and strength of recommendation. International guidelines exist on the management of infection in the diabetic foot. Many randomized trials have been performed, and these have shown that the agents studied generally produced comparable results, with the exception of one study in which tigecycline was shown to be clinically inferior to ertapenem±vancomycin. Similarly, there are numerous types of wound dressings that might be used in treatment and which have shown efficacy, but no single type (or brand) has shown superiority over others. Peripheral arterial disease is another major contributory factor in the development of ulceration, and its presence is a strong predictor of non-healing and amputation. Despite the proliferation of endovascular procedures in addition to open revascularization, many patients continue to suffer from severely impaired perfusion and exhaust all treatment options. Finally, the question of the true aetiopathogenesis of Charcot neuroarthropathy remains enigmatic, although much work is currently being undertaken in this area. In this area, it is most important to remember that a clinically uninfected, warm, insensate foot in a diabetic patient should be considered as a Charcot foot until proven otherwise, and, as such, treated with offloading, preferably in a cast. This article is protected by copyright. All rights reserved.
    No preview · Article · Oct 2015 · Diabetes/Metabolism Research and Reviews
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    Full-text · Article · Oct 2015 · Diabetes Care

  • No preview · Article · Aug 2015 · Diabetes care
  • Frank L Bowling · S Tawqeer Rashid · Andrew J M Boulton
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    ABSTRACT: Diabetes mellitus is associated with a series of macrovascular and microvascular changes that can manifest as a wide range of complications. Foot ulcerations affect ∼2-4% of patients with diabetes mellitus. Risk factors for foot lesions include peripheral and autonomic neuropathy, vascular disease and previous foot ulceration, as well as other microvascular complications, such as retinopathy and end-stage renal disease. Ulceration is the result of a combination of components that together lead to tissue breakdown. The most frequently occurring causal pathways to the development of foot ulcers include peripheral neuropathy and vascular disease, foot deformity or trauma. Peripheral vascular disease is often not diagnosed in patients with diabetes mellitus until tissue loss is evident, usually in the form of a nonhealing ulcer. Identification of patients with diabetes mellitus who are at high risk of ulceration is important and can be achieved via annual foot screening with subsequent multidisciplinary foot-care interventions. Understanding the factors that place patients with diabetes mellitus at high risk of ulceration, together with an appreciation of the links between different aspects of the disease process, is essential to the prevention and management of diabetic foot complications.
    No preview · Article · Aug 2015 · Nature Reviews Endocrinology
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    ABSTRACT: To examine the stepping accuracy of people with diabetes and diabetic peripheral neuropathy. A total of 14 patients with diabetic peripheral neuropathy, 12 patients with diabetes but no neuropathy (diabetes-alone group) and 10 healthy control subjects took part in the study. Accuracy of stepping was measured whilst the participants walked along a walkway consisting of 18 stepping targets. Preliminary data on visual gaze characteristics were also captured in a subset of participants (diabetic peripheral neuropathy group: n = 4; diabetes-alone group: n = 4; and control group: n = 4) during the same task. Patients with diabetic peripheral neuropathy were significantly less accurate at stepping on targets than were control subjects (P<0.05). Preliminary visual gaze analysis identified that patients diabetic peripheral neuropathy were slower to look between targets, resulting in less time being spent looking at a target before foot-target contact. Impaired motor control is theorized to be a major factor underlying the changes in stepping accuracy, and potentially altered visual gaze behaviour may also play a role. Reduced stepping accuracy may indicate a decreased ability to control the placement of the lower limbs, leading to patients with neuropathy potentially being less able to avoid observed obstacles during walking. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    Full-text · Article · Jul 2015 · Diabetic Medicine
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    Full-text · Article · Jul 2015 · Diabetes care
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    ABSTRACT: To examine the effects of a 16-week resistance exercise training intervention on the speed of ankle and knee strength generation during stair ascent and descent, in people with neuropathy. A total of 43 people: nine with diabetic peripheral neuropathy, 13 with diabetes but no neuropathy and 21 healthy control subjects ascended and descended a custom-built staircase. The speed at which ankle and knee strength were generated, and muscle activation patterns of the ankle and knee extensor muscles were analysed before and after a 16-week intervention period. Ankle and knee strength generation during both stair ascent and descent were significantly higher after the intervention than before the intervention in the people with diabetes who undertook the resistance exercise intervention (P<0.05). Although muscle activations were altered by the intervention, there were no observable patterns that underpinned the observed changes. The increased speed of ankle and knee strength generation observed after the intervention would be expected to improve stability during the crucial weight acceptance phase of stair ascent and descent, and ultimately contribute towards reducing the risk of falling. Improvements in muscle strength as a result of the resistance exercise training intervention are likely to be the most influential factor for increasing the speed of strength generation. It is recommended that these exercises could be incorporated into a multi-faceted exercise programme to improve safety in people with diabetes and neuropathy. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    Full-text · Article · Jun 2015 · Diabetic Medicine
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    ABSTRACT: Unlabelled: Objective. A cross sectional study was developed to investigate ethnic differences in foot pressure and joint mobility in non-diabetic and diabetic subjects with and without neuropathy in a hospital-based diabetes clinic. Methods: The subject groups consisted of a volunteer sample of 10 Asians (AC), 11 Europid non-diabetic controls (C), a consecutive sample of 12 Asians (ADC) and 11 Europid (DC) non-neuropathic patients, and 12 Asian (ADN) and 13 Europid (DN) neuropathic diabetic patients. All subjects were matched with respect to age and gender. The main outcome measures were foot pressures and joint mobility. Results: Peak foot pressure was increased in DN (1150 ± 412 kPa, mean ± SD) compared to AC, ADC, ADN, C, and DC (510 ± 164 kPa, 673 ± 331 kPa, 623 ± 222 kPa, 707 ± 240 kPa, 793 ± 196 kPa, respectively; P < 0.05). Passive range of motion of the subtalar joint, ankle (AC only), first metatarsophalangeal and fifth metacarpophalangeal joints (MCJP) were reduced in DN compared to the Asian controls and diabetic patients (P < 0.05). Dynamic ankle and rearfoot (subtalar) joint angles were not different among groups. Only the fifth MCJP extension had an effect on peak plantar pressure while controlling for ethnicity (P < 0.05). Conclusion: Peak foot pressure was higher and joint mobility was lower in Europid compared to Asian diabetic neuropathic patients; however, no relationship was observed between reduced foot joint mobility and increased foot pressures. The association between fifth MCJP extension and peak pressure suggest that fifth MCJP extension may be used as a screening method for increased pressure. The low foot pressures exhibited by the Asian subjects are most likely caused by factors other than those investigated in this study.
    No preview · Article · Apr 2015 · Wounds: a compendium of clinical research and practice
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    ABSTRACT: Impaired glucose tolerance (IGT) through to type 2 diabetes is thought to confer a continuum of risk for neuropathy. Identification of subjects at high risk of developing type 2 diabetes and, hence, worsening neuropathy would allow identification and risk stratification for more aggressive management. 30 subjects with IGT and 17 age-matched control subjects underwent an oral glucose tolerance test, assessment of neuropathic symptoms and deficits, quantitative sensory testing, neurophysiology, skin biopsy, and corneal confocal microscopy (CCM) to quantify corneal nerve fiber density (CNFD), branch density (CNBD), and fiber length (CNFL) at baseline and annually for 3 years. Ten subjects who developed type 2 diabetes had a significantly lower CNFD (P = 0.003), CNBD (P = 0.04), and CNFL (P = 0.04) compared with control subjects at baseline and a further reduction in CNFL (P = 0.006), intraepidermal nerve fiber density (IENFD) (P = 0.02), and mean dendritic length (MDL) (P = 0.02) over 3 years. 15 subjects who remained IGT and 5 subjects who returned to normal glucose tolerance had no significant baseline abnormality on CCM or IENFD but had a lower MDL (P < 0.0001) compared with control subjects. The IGT subjects showed a significant decrease in IENFD (P = 0.02) but no change in MDL or CCM over 3 years. Those who returned to NGT showed an increase in CNFD (P = 0.05), CNBD (P = 0.04), and CNFL (P = 0.05), but a decrease in IENFD (P = 0.02), over 3 years. CCM and skin biopsy detect a small-fiber neuropathy in subjects with IGT who develop type 2 diabetes and also show a dynamic worsening or improvement in corneal and intraepidermal nerve morphology in relation to change in glucose tolerance status. © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.
    Full-text · Article · Apr 2015 · Diabetes care
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    ABSTRACT: Patients with diabetes with peripheral neuropathy have a well-recognized increased risk of falls that may result in hospitalization. Therefore this study aimed to assess balance during the dynamic daily activities of walking on level ground and stair negotiation, where falls are most likely to occur. Gait analysis during level walking and stair negotiation was performed in 22 patients with diabetic neuropathy (DPN), 39 patients with diabetes without neuropathy (D), and 28 nondiabetic control subjects (C) using a motion analysis system and embedded force plates in a staircase and level walkway. Balance was assessed by measuring the separation between the body center of mass and center of pressure during level walking, stair ascent, and stair descent. DPN patients demonstrated greater (P < 0.05) maximum and range of separations of their center of mass from their center of pressure in the medial-lateral plane during stair descent, stair ascent, and level walking compared with the C group, as well as increased (P < 0.05) mean separation during level walking and stair ascent. The same group also demonstrated greater (P < 0.05) maximum anterior separations (toward the staircase) during stair ascent. No differences were observed in D patients. Greater separations of the center of mass from the center of pressure present a greater challenge to balance. Therefore, the higher medial-lateral separations found in patients with DPN will require greater muscular demands to control upright posture. This may contribute to explaining why patients with DPN are more likely to fall, with the higher separations placing them at a higher risk of experiencing a sideways fall than nondiabetic control subjects. © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.
    Full-text · Article · Mar 2015 · Diabetes Care
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    ABSTRACT: Corneal confocal microscopy is a novel diagnostic technique for the detection of nerve damage and repair in a range of peripheral neuropathies, in particular diabetic neuropathy. Normative reference values are required to enable clinical translation and wider use of this technique. We have therefore undertaken a multicenter collaboration to provide worldwide age-adjusted normative values of corneal nerve fiber parameters. A total of 1,965 corneal nerve images from 343 healthy volunteers were pooled from six clinical academic centers. All subjects underwent examination with the Heidelberg Retina Tomograph corneal confocal microscope. Images of the central corneal subbasal nerve plexus were acquired by each center using a standard protocol and analyzed by three trained examiners using manual tracing and semiautomated software (CCMetrics). Age trends were established using simple linear regression, and normative corneal nerve fiber density (CNFD), corneal nerve fiber branch density (CNBD), corneal nerve fiber length (CNFL), and corneal nerve fiber tortuosity (CNFT) reference values were calculated using quantile regression analysis. There was a significant linear age-dependent decrease in CNFD (-0.164 no./mm(2) per year for men, P < 0.01, and -0.161 no./mm(2) per year for women, P < 0.01). There was no change with age in CNBD (0.192 no./mm(2) per year for men, P = 0.26, and -0.050 no./mm(2) per year for women; P = 0.78). CNFL decreased in men (-0.045 mm/mm(2) per year, P = 0.07) and women (-0.060 mm/mm(2) per year, P = 0.02). CNFT increased with age in men (0.044 per year, P < 0.01) and women (0.046 per year, P < 0.01). Height, weight, and BMI did not influence the 5th percentile normative values for any corneal nerve parameter. This study provides robust worldwide normative reference values for corneal nerve parameters to be used in research and clinical practice in the study of diabetic and other peripheral neuropathies. © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.
    Full-text · Article · Jan 2015 · Diabetes Care
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    Full-text · Article · Jan 2015 · Diabetes Care
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    Full-text · Article · Dec 2014 · Journal of Clinical Endocrinology & Metabolism
  • Andrew J M Boulton
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    ABSTRACT: Foot ulceration and Charcot neuroarthropathy (CN) are well recognized and documented late sequelae of diabetic peripheral, somatic, and sympathetic autonomic neuropathy. The neuropathic foot, however, does not ulcerate spontaneously: it is a combination of loss of sensation due to neuropathy together with other factors such as foot deformity and external trauma that results in ulceration and indeed CN. The commonest trauma leading to foot ulcers in the neuropathic foot in Western countries is from inappropriate footwear. Much of the management of the insensate foot in diabetes has been learned from leprosy which similarly gives rise to insensitive foot ulceration. No expensive equipment is required to identify the high risk foot and recently developed tests such as the Ipswich Touch Test and the Vibratip have been shown to be useful in identifying the high risk foot. A comprehensive screening program, together with education of high risk patients, should help to reduce the all too high incidence of ulceration in diabetes. More recently another very high risk group has been identified, namely patients on dialysis, who are at extremely high risk of developing foot ulceration; this should be preventable. The most important feature in management of neuropathic foot ulceration is offloading as patients can easily walk on active foot ulcers due to the loss of pain sensation. Infection should be treated aggressively and if there is any evidence of peripheral vascular disease, arteriography and appropriate surgical management is also indicated. CN often presents with a unilateral hot, swollen foot and any patient presenting with these features known to have neuropathy should be treated as a Charcot until this is proven otherwise. Most important in the management of acute CN is offloading, often in a total contact cast.
    No preview · Article · Nov 2014 · Handbook of Clinical Neurology
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    ABSTRACT: The Journal of family Prac Tice | n oV e mBe r 2 0 1 4 | V o l 6 3 , n o 1 1 The 3-minute diabetic foot exam Early detection of diabetes-related foot problems can be lifesaving. This brief exam will help you to quickly detect major risks and prompt you to refer patients to appropriate specialists. F oot ulcers and other lower-limb complications sec-ondary to diabetes are common, complex, costly, and associated with increased morbidity and mortality. 1-6 Unfortunately, patients often have difficulty recognizing the heightened risk status that accompanies the diagnosis of dia-betes, particularly the substantial risk for lower limb compli-cations. 7 In addition, loss of protective sensation (LOPS) can render patients unable to recognize damage to their lower extremities, thus creating a cycle of tissue damage and other foot complications. Strong evidence suggests that consistent provision of foot-care services and preventive care can re-duce amputations among patients with diabetes. 7-9 However, routine foot examination and rapid risk stratification is often difficult to incorporate into busy primary care settings. Data suggest that the diabetic foot is adequately evaluated only 12% to 20% of the time. 10 In response to the need for more consistent foot exams, an American Diabetes Association (ADA) task force lead by 2 of the authors of this article (AB and DA) created the Compre-hensive Foot Examination and Risk Assessment. 5 This set the standard for the detailed investigation of lower limb pathol-ogy by a specialist, but was not well suited for other practice settings, including primary care. One reason is that it would be difficult to complete the comprehensive examination dur-ing a typical 15-minute primary care office visit. In addition, certain examination parameters require the use of neurologic and vascular assessment equipment and training not avail-able in all health care settings. 11 With these thoughts in mind, we set out to develop an exam that could be done by a wide range of health care pro-viders—one that takes substantially less time to complete than a comprehensive exam and eliminates common barri-ers to frequent assessment. The exam, which we'll describe here, consists of 3 components: taking a patient history, performing a physical exam, and
    Full-text · Article · Nov 2014 · The Journal of family practice
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    ABSTRACT: This brief exam will help you to quickly detect major risks and prompt you to refer patients to appropriate specialists.
    Full-text · Article · Nov 2014 · The Journal of family practice
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    ABSTRACT: We, as representatives of scientific organizations devoted to improving health care and advancing research, reaffirm that it is the mission of our respective medical journals to report and disseminate data from scientific investigation, evolving medical care, and innovative treatments. We believe these reports serve to unite basic scientists, clinical investigators, and medical professionals regardless of their country of origin, ethnic group, or political leaning. We believe that these efforts achieve the common goal of advancing scientific discoveries that lead to improved health of people worldwide. On the basis of our goals and principles, our respective journals will refrain from publishing articles addressing political issues that are outside of either research funding or health care delivery.
    Preview · Article · Oct 2014 · Endocrine Practice

Publication Stats

24k Citations
2,334.44 Total Impact Points


  • 2009-2016
    • Central Manchester University Hospitals NHS Foundation Trust
      • • Manchester Diabetes Centre
      • • Diabetes Centre
      Manchester, England, United Kingdom
    • William Penn University
      Filadelfia, Pennsylvania, United States
  • 1994-2015
    • The University of Manchester
      • • Manchester Medical School
      • • School of Biomedicine
      Manchester, England, United Kingdom
    • University of Kent
      Cantorbery, England, United Kingdom
    • Pennsylvania State University
      • Center for Locomotion Studies
      University Park, MD, United States
    • Manchester Mental Health and Social Care Trust
      Manchester, England, United Kingdom
  • 2012
    • WWF United Kingdom
      Londinium, England, United Kingdom
  • 1985-2012
    • University of Miami Miller School of Medicine
      • • Endocrinology, Diabetes and Metabolism Division
      • • Division of Hospital Medicine
      • • Division of General Internal Medicine
      • • Department of Medicine
      Miami, Florida, United States
  • 1984-2011
    • University of Miami
      • • Department of Medicine
      • • Diabetes Research Institute
      كورال غيبلز، فلوريدا, Florida, United States
  • 1992-2009
    • Diabetes UK
      Londinium, England, United Kingdom
    • University of Aberdeen
      Aberdeen, Scotland, United Kingdom
  • 2006
    • Columbia University
      • Department of Surgery
      New York City, NY, United States
  • 2004-2006
    • Rosalind Franklin University of Medicine and Science
      • The Dr. William M. Scholl College of Podiatric Medicine
      North Chicago, Illinois, United States
    • Universities UK
      Londinium, England, United Kingdom
    • Albert Einstein College of Medicine
      New York, New York, United States
  • 2005
    • University of Amsterdam
      Amsterdamo, North Holland, Netherlands
    • University of Toronto
      Toronto, Ontario, Canada
  • 2003-2005
    • Johns Hopkins University
      • Department of Pediatrics
      Baltimore, Maryland, United States
    • Loyola University Chicago
      • Department of Orthopaedic Surgery and Rehabilitation
      Chicago, Illinois, United States
  • 2001-2003
    • The Bracton Centre, Oxleas NHS Trust
      Дартфорде, England, United Kingdom
    • Queens University of Charlotte
      New York, United States
  • 2002
    • University of Maryland, Baltimore
      Baltimore, Maryland, United States
  • 1996
    • Manchester Memorial Hospital
      Manchester, Connecticut, United States
  • 1995
    • Imperial College Healthcare NHS Trust
      Londinium, England, United Kingdom
  • 1991
    • University of Liverpool
      • School of Medicine
      Liverpool, England, United Kingdom
  • 1987
    • The Royal Society of Medicine
      Londinium, England, United Kingdom
  • 1986
    • Sheffield Teaching Hospitals NHS Foundation Trust
      Sheffield, England, United Kingdom
    • The University of Sheffield
      • Department of Psychology (Faculty of Science)
      Sheffield, England, United Kingdom