Pediatric preseptal and orbital cellulitis - a 6 year experience from a London tertiary centre.

PURPOSE: This study reports the experience of pediatric preseptal and orbital cellulitis at a London tertiary centre during a 6-year period and highlights the role of orbital surgeons in the management of subperiosteal abscess (SPA). METHODS: A retrospective review was conducted of all pediatric patients hospitalised for preseptal and orbital cellulitis. RESULTS: A total of 201 children including 152 cases of preseptal cellulitis and 49 cases of orbital cellulitis were admitted at a London tertiary centre over the study period. Patients with orbital cellulitis and especially those managed surgically had higher rates of fever, higher presenting white cell count and C-reactive protein level compared to cases of preseptal cellulitis. 77.6% of patients with orbital cellulitis had SPA. 81.6% of SPA had a medial component, while 28.9% had superior component. 61.2% of orbital cellulitis cases were managed surgically. Surgical intervention was carried out by otorhinolaryngologists (ENT) in 76.7% of cases, jointly between ENT and orbital surgeons in 16.7% of cases and by orbital surgeons alone in 6.7% of cases. Of the 11 SPA involving the orbital roof, all were surgically managed and orbital surgeons were involved in 54.5% of cases. When SPA involved the medial wall, orbital surgeons were only involved in 6.5% of cases. CONCLUSIONS: We recommend all patients with superior SPA be treated at a centre with both ENT and orbital surgeons as these may not be amenable to drainage by ENT alone.

Women with depression in pregnancy or a history of depression have decreased quality of mentalization in the speech to their infants.

BACKGROUND: Our study aims to understand whether depression, either in pregnancy or lifetime, affects cognitive biases (comprising the attentional focus and affective state) and mentalizing features (ability to understand children's internal mental states, thereby detecting and comprehending their behavior and intention), in maternal speech during mother-infant interaction in the first postnatal year. METHODS: We recruited 115 pregnant women (44 healthy, 46 with major depressive disorder [MDD] in pregnancy, and 25 with a history of MDD but healthy pregnancy) at 25 weeks' gestation. Three-minute videos were recorded at 8 weeks and 12 months postnatally for each dyad. Maternal speech was transcribed verbatim and coded for cognitive biases and mentalizing comments using the Parental Cognitive Attributions and Mentalization Scale (PCAMs). RESULTS: Women suffering from antenatal depression showed a decreased proportion of mentalizing comments compared with healthy women, at both 8 weeks (0.03 ± 0.01 vs. 0.07 ± 0.01, P = 0.002) and 12 months (0.02 ± 0.01 vs. 0.04 ± 0.01, P = 0.043). Moreover, compared with healthy women, both those with antenatal depression and those with a history of depression showed decreased positive affection in speech (0.13 ± 0.01 vs. 0.07 ± 0.01 and 0.08 ± 0.02, respectively P = 0.003 and P = 0.043), and made significantly fewer comments focused on their infants' experience at 8 weeks (0.67 ± 0.03 vs. 0.53 ± 0.04 and 0.49 ± 0.05, respectively P = 0.015 and P = 0.005). In linear regression models women's socioeconomic difficulties and anxiety in pregnancy contribute to these associations, while postnatal depression did not. CONCLUSIONS: Both antenatal depression and a lifetime history of depression are associated with a decreased quality of women's speech to their infants, as shown by less focus on their infant's experience, decreased positive affection, and less able to mentalize. Examining maternal speech to their infants in the early postnatal months may be particularly relevant to identify women who could benefit from strategies addressing these aspects of the interactive behavior and thus improve infant outcome in the context of depression.

Combined upper lid skin crease and endoscopic approach to frontal sinus mucocoeles.

PURPOSE: This case series describes the ophthalmic manifestations of frontal sinus mucoceles and reports the long-term surgical outcomes of a combined endoscopic and upper-lid skin crease drainage approach carried out jointly with otorhinolaryngology. METHODS: We present a retrospective case review of 18 orbits and 15 patients presenting with frontal sinus mucocoeles, all of whom underwent drainage via an adapted anterior orbitotomy approach between January 2015 and July 2023. Data collection included preoperative and postoperative examination findings (visual acuity, extraocular motility, lid retraction, and lagophthalmos), mucocoele recurrence, cosmetic satisfaction, and surgical complications. Patients were followed up for an average of 22 months. RESULTS: All patients underwent successful frontal mucocoele drainage via a modified anterior orbitotomy and simultaneous endonasal approach. At presentation, three (20%) had extraocular restriction leading to diplopia, and six (40%) had proptosis in the eye adjacent to the mucocoele. One patient presented acutely with no light perception in the affected eye due to compressive optic neuropathy. All patients who had reduced extraocular motility before surgery regained full motility post-operatively. Treatment was successful in all cases, and there was no documented mucocoele recurrence during follow-up. Satisfactory aesthetic outcomes were achieved in all cases. Reported complications included temporary forehead numbness and ptosis of the affected eyelid, which resolved without intervention. CONCLUSION: The modified anterior orbitotomy approach to frontal mucocoeles allows optimal frontal sinus access and mucocoele treatment while preserving cosmesis.

A multidisciplinary approach to frontal sinus mucocoeles using an upper lid skin crease incision combined with endoscopic drainage allows full access to the frontal sinus and treatment of the mucocoele while preserving cosmesis.

Increased maternal inflammation and poorer infant neurobehavioural competencies in women with a history of major depressive disorder from the psychiatry research and motherhood - Depression (PRAM-D) study.

INTRODUCTION: Stress in pregnancy is associated with adverse outcomes in offspring, and developmental programming is a potential mechanism. We have previously shown that depression in pregnancy is a valid and clearly defined stress paradigm, and both maternal antenatal and offspring stress-related biology is affected. This study aims to clarify whether maternal biology in pregnancy and offspring outcomes can also be influenced by a history of a prior depression, in the absence of depression in pregnancy. Our primary hypothesis is that, similarly to women with depression in pregnancy, women with a history of depression but who are not depressed in pregnancy will have increased cortisol secretion and markers of immune system function, and that their offspring will have poorer neuro-developmental competencies and increased cortisol stress response. METHODS: A prospective longitudinal design was used in 59 healthy controls and 25 women with a past history of depression who were not depressed in pregnancy, named as 'history-only', and their offspring. Maternal antenatal stress-related biology (cortisol and markers of immune system function) and offspring outcomes (gestational age at birth, neonatal neurobehaviour (Neonatal Behavioural Assessment Scale, NBAS), cortisol stress response and basal cortisol at 2 and 12 months) and cognitive, language and motor development (Bayley Scales of Infant and Toddler Development (BSID)) were measured. RESULTS: Compared with healthy pregnant women, those with a history of depression who remain free of depression in pregnancy exhibit increased markers of immune system function in pregnancy: IL-8 (d = 0.63, p = 0.030), VEGF (d = 0.40, p = 0.008) and MCP-1 (d = 0.61, p = 0.002) and have neonates with lower neurobehavioural scores in most areas, reaching statistical significance in thesocial-interactive (d = 1.26, p = 0.015) cluster. However, there were no differences in maternal or offspring HPA axis function or in infant development at 12 months. CONCLUSION: Our study indicates that pregnant women with a history of depression have increased markers of immune system function, and their offspring show behavioural alterations that may be the effects of in utero programming, epigenetic factors or genetic predisposition.

Elite UK winter wheat cultivars differ in their ability to support the colonization of beneficial root-infecting fungi.

In numerous countries, Gaeumannomyces species, within the Magnaporthaceae family, have previously been implicated in the suppression of take-all root disease in wheat. A UK arable isolate collection (n=47) was gathered and shown to contain Gaeumannomyces hyphopodioides and an unnamed Magnaporthaceae species. A novel seedling pot bioassay revealed that both species had a similar ability to colonize cereal roots; however, rye (Secale cereale) was only poorly colonized by the Magnaporthaceae species. To evaluate the ability of 40 elite UK winter wheat cultivars to support soil inoculum of beneficial soil-dwelling fungi, two field experiments were carried out using a naturally infested arable site in south-east England. The elite cultivars grown in the first wheat situation differed in their ability to support G. hyphopodioides inoculum, measured by colonization on Hereward as the subsequent wheat in a seedling soil core bioassay. In addition, the root colonization ability of G. hyphopodioides was influenced by the choice of the second wheat cultivar. Nine cultivars supported the colonization of the beneficial root fungus. Our findings provide evidence of complex host genotype-G. hyphopodioides interactions occurring under field conditions. This new knowledge could provide an additional soil-based crop genetic management strategy to help combat take-all root disease.

Frontal Sinus Mucocele Formation as a Late Complication of External Dacrocystorhinostomy.

Two cases of frontal sinus mucocele post external approach dacrocystorhinostomy (DCR) surgery are reported. The possible anatomical causes of this condition are discussed and in particular, attention is drawn to the consideration of frontal sinus mucocele in patients presenting with frontal sinus symptoms post-DCR surgery.

Long-term spatiotemporal stability and dynamic changes in helminth infracommunities of bank voles (Myodes glareolus) in NE Poland.

Parasites are considered to be an important selective force in host evolution but ecological studies of host-parasite systems are usually short-term providing only snap-shots of what may be dynamic systems. We have conducted four surveys of helminths of bank voles at three ecologically similar woodland sites in NE Poland, spaced over a period of 11 years, to assess the relative importance of temporal and spatial effects on helminth infracommunities. Some measures of infracommunity structure maintained relative stability: the rank order of prevalence and abundance of Heligmosomum mixtum, Heligmosomoides glareoli and Mastophorus muris changed little between the four surveys. Other measures changed markedly: dynamic changes were evident in Syphacia petrusewiczi which declined to local extinction, while the capillariid Aonchotheca annulosa first appeared in 2002 and then increased in prevalence and abundance over the remaining three surveys. Some species are therefore dynamic and both introductions and extinctions can be expected in ecological time. At higher taxonomic levels and for derived measures, year and host-age effects and their interactions with site are important. Our surveys emphasize that the site of capture is the major determinant of the species contributing to helminth community structure, providing some predictability in these systems.

Necrotizing Blepharoconjunctivitis and Keratitis in Human Monkeypox.

Importance: Ophthalmic manifestations occur in less than 5% of patients with human mpox (monkeypox), most commonly presenting with self-limiting conjunctivitis and keratitis. Cases with severe ophthalmic complication are uncommon. Objective: To present a case of human mpox with sight-threatening necrotizing blepharoconjunctivitis. Design, Setting, and Participants: This is a report of a patient who developed necrotizing conjunctivitis due to the monkepox virus at a large university hospital. Data were collected from July to October 2022. Main Outcomes and Measures: Description of the progression and clinical evaluation of the ocular condition and the management. Results: A 63-year-old HIV-positive man presented initially with conjunctivitis and eyelid swelling and developed skin lesions from monkeypox virus 2 days later. Despite remaining stable systemically, after 4 days, his ophthalmic condition evolved to necrotizing blepharoconjunctivitis for which systemic antiviral treatment with tecovirimat was given along with topical trifluoridine, 1%, eye drops. In addition, he required repeated tissue debridement with amniotic membrane grafting to preserve the eye integrity. Conclusions and Relevance: The severity of this observation was associated with a coexisting immunocompromised state and appeared similar to findings associated with other orthopoxviruses. Ophthalmic manifestations could be the initial presentation of human mpox and could also be severe. Early recognition and intervention may limit the likelihood of substantial ocular morbidity.

Corneal Neurotization Using the Great Auricular Nerve for Bilateral Congenital Trigeminal Anesthesia.

PURPOSE: The purpose of this study was to describe an indirect corneal neurotization (CN) technique for congenital bilateral trigeminal anesthesia using the greater auricular nerve (GAN) as a donor. METHOD: CN was performed to preserve the integrity of the only seeing eye in a 4-year-old boy with pontine tegmental cap dysplasia and bilateral trigeminal anesthesia. He had recurrent corneal ulceration and scarring despite full medical treatment. The GAN was used as a donor, and the sural nerve was harvested and used as a bridge which was tunneled to the sub-Tenon space in the inferior fornix. The fascicles were distributed into the 4 quadrants and sutured to the sclera near the limbus. RESULT: This technique resulted in providing corneal sensation and improving stability of the epithelium. Corneal opacity gradually decreased allowing significant visual improvement evidenced in the early postoperative months. CONCLUSIONS: Using the GAN technique for CN bypasses trigeminal innervation and has the potential to improve corneal sensation. The GAN is a large caliber nerve and provides a large amount of axons and robust neurotization. This technique would be desirable for cases with bilateral congenital trigeminal anesthesia, such as pontine tegmental cap dysplasia.

Frontal sinus mucocele with orbital extension drained via a combined upper lid skin crease and endoscopic approach.

This case report discusses the ophthalmic complications of frontal sinus mucoceles and describes the favorable long-term surgical outcomes of a combined endoscopic and upper-lid skin crease drainage approach carried out jointly with otorhinolaryngology. A 47-year-old single mother presented to eye casualty with markedly swollen eyelids and visual acuity of 6/6 in the left eye, no perception of light in the right. Ophthalmic examination revealed right-sided hypoglobus and proptosis with exposure keratopathy inferiorly. There was complete ophthalmoplegia in the right eye and a hemorrhagic optic disc visible on fundoscopy. CT orbit with contrast confirmed a diagnosis of giant frontal mucocele with orbital extension. The patient underwent mucocele drainage via a modified anterior orbitotomy approach and FESS (Functional Endoscopic Sinus Surgery) drainage performed jointly with otorhinolaryngology. Two weeks post-operatively her proptosis was resolving and by three months she had regained full extraocular motility. As expected, vision was not restored in the right eye. At one year, the patient's upper lid skin crease scar was completely buried in the eyelid's natural contour, and repeat CT scanning confirmed no re-stenosis or mucocele recurrence. This case demonstrates, that a multidisciplinary approach to far-lateral frontal sinus mucoceles with orbital extension and ophthalmic complications which combines an upper lid skin crease incision with FESS drainage, allows adequate access to the frontal sinus while preserving cosmesis.

Modified eyelid crease approach frontalis suspension without brow incision.

A 10-year-old boy with Noonan syndrome presented with bilateral ptosis. He had a history of keloid scarring. A modified technique of frontalis suspension with autogenous fascia lata is described to avoid forehead wounds. This uses an eyelid crease incision, dissection under the orbicularis to the orbital rim, and passage of the fascia lata into a shallow arc through the frontalis muscle. It is then passed inferiorly through the septum and secured to the tarsus.

Mother-infant interaction in women with depression in pregnancy and in women with a history of depression: the Psychiatry Research and Motherhood - Depression (PRAM-D) study.

BACKGROUND: Little is known about the effects of depression before birth on the quality of the mother-infant interaction. AIMS: To understand whether depression, either in pregnancy or in lifetime before pregnancy, disrupts postnatal mother-infant interactions. METHOD: We recruited 131 pregnant women (51 healthy, 52 with major depressive disorder (MDD) in pregnancy, 28 with a history of MDD but healthy pregnancy), at 25 weeks' gestation. MDD was confirmed with the Structured Clinical Interview for DSM-IV Disorders. Neonatal behaviour was assessed at 6 days with the Neonatal Behavioural Assessment Scale, and mother-infant interaction was assessed at 8 weeks and 12 months with the Crittenden CARE-Index. RESULTS: At 8 weeks and 12 months, dyads in the depression and history-only groups displayed a reduced quality of interaction compared with healthy dyads. Specifically, at 8 weeks, 62% in the depression group and 56% in the history-only group scored in the lowest category of dyadic synchrony (suggesting therapeutic interventions are needed), compared with 37% in the healthy group (P = 0.041); 48% and 32%, respectively, scored the same at 12 months, compared with 14% in the healthy group (P = 0.003). At 6 days, neonates in the depression and history-only groups exhibited decreased social-interactive behaviour, which, together with maternal socioeconomic difficulties, was also predictive of interaction quality, whereas postnatal depression was not. CONCLUSIONS: Both antenatal depression and a lifetime history of depression are associated with a decreased quality of mother-infant interaction, irrespective of postnatal depression. Clinicians should be aware of this, as pregnancy provides an opportunity for identification and intervention to support the developing relationship.

Risk factors for postpartum relapse in women at risk of postpartum psychosis: The role of psychosocial stress and the biological stress system.

BACKGROUND: Postpartum psychosis is the most severe psychiatric disorder associated with childbirth, and the risk is particularly high for women with a history of bipolar disorder, schizoaffective disorder or those who have suffered a previous episode of postpartum psychosis. Whilst there is a lot of evidence linking stress to psychosis unrelated to childbirth, the role of stress in the onset of postpartum psychosis has not been fully investigated. METHODS: A prospective longitudinal study of 112 pregnant women, 51 at risk of postpartum psychosis because of a DSM-IV diagnosis of bipolar disorder (n = 41), schizoaffective disorder (n = 6) or a previous postpartum psychosis (n = 4) and 61 healthy women with no past or current DSM-IV diagnosis and no family history of postpartum psychosis. Women were followed up from the third trimester of pregnancy to 4 weeks' post partum. Women at risk who had a psychiatric relapse in the first 4 weeks' post partum (AR-unwell) (n = 22), were compared with those at risk who remained well (AR-well) (n = 29) on measures of psychosocial stress (severe childhood maltreatment and stressful life events) and biological stress (cortisol and inflammatory biomarkers). RESULTS: Logistic regression analyses revealed that severe childhood maltreatment (OR = 4.9, 95% CI 0.5-49.2) and higher daily cortisol in the third trimester of pregnancy (OR=3.7, 95% CI 1.2-11.6) predicted psychiatric relapse in the first 4 weeks' post partum in women at risk of postpartum psychosis after adjusting for clinical and sociodemographic covariates. CONCLUSION: The current study provides evidence for the role of psychosocial stress and the biological stress system in the risk of postpartum relapse in women at risk of postpartum psychosis.

Determination of the function of a repaired canaliculus after monocanalicular injury by placing a punctal plug in the non-involved punctum on the affected side.

BACKGROUND: To determine whether repair of a monocanalicular laceration using a Mini-Monoka stent provides a functioning system. METHODS: This prospective study included patients who underwent repair of a monocanalicular laceration with placement of a Mini-Monoka stent. Silicone punctal plugs were placed in the unaffected punctum on the side that had sustained the injury and in the same punctum on the fellow eye. The plug was left in place for between 7 and 17 days. The patient was questioned after placement regarding symptoms of epiphora. RESULTS: Eight patients were included in the study; five injuries involved the lower canaliculus, two the upper, and one the upper and lower but only the lower was repaired. Of injuries, 50% were as a result of assault. Seven out of eight patients had no epiphora from the repaired eye during plug placement. One patient complained of significant epiphora from the repaired eye during the time the plugs were placed; this patient had a partial nasolacrimal duct obstruction and no canalicular stenosis. Of patients, 88% had an anatomically patent canaliculus and 100% were tearing-free when no plug was placed. CONCLUSIONS: In this study, a repaired monocanalicular injury provided a functioning system in 88% of cases. In previous studies, it has been shown that many patients are symptom-free with just one functioning canaliculus. However, a fully functioning canalicular system may help to prevent tearing under stress conditions, and will provide a viable system if the other canaliculus is irreparably damaged in the future. Therefore, repair is recommended.

The use of fibrin tissue glue in the repair of cicatricial ectropion of the lower eyelid.

PURPOSE: To evaluate the effectiveness of full-thickness skin graft adhesion using fibrin tissue glue (TISSEEL) in cicatricial ectropion repair of the lower eyelid. METHOD: This study was a prospective case series. Nine eyes of 8 consecutive patients with cicatricial ectropion were included. All patients underwent a conjunctival approach lower eyelid retractor plication, lateral tarsal strip, and insertion of a full-thickness skin graft secured with TISSEEL. Symptoms of epiphora, eye and eyelid irritation, discharge, and graft size were recorded pre- and postoperatively. RESULTS: All of the patients were satisfied with their postoperative appearance, and the symptoms of eye and eyelid irritation, discharge, and visual disturbance were eliminated. Fifty-five percent of patients had complained of watering some or all of the time preoperatively, whereas only 33% admitted to occasional watering postoperatively. The average size of the graft reduced by 18% at 1 week, 39% at 1 month, and 40% at 3 months from the initial size. CONCLUSIONS: Fibrin tissue glue used to attach a full-thickness skin graft during cicatricial ectropion repair is an effective technique and may offer additional benefits over sutured graft fixation. Most of the reduction in graft size occurred in the first postoperative month, which indicates that the time window for modulation of the graft is in the first few weeks after surgery. The vertical graft length was affected to a greater extent than the horizontal length.

Epithelial inclusion cyst associated with a porous polyethylene orbital floor implant.

A 50-year-old man presented with reduced vision, hyperglobus, and an inferior orbital mass 3(1/2) years after the repair of an orbital floor fracture using a porous polyethylene (Medpor) implant. On funduscopy, the sclera was markedly indented. This was associated with retinal striae and a retinal pigment epithelial disturbance involving the macula. CT revealed a large inferior orbital cystic mass displacing the globe. The cyst was excised and the orbital implant was removed. Histologic findings were consistent with a respiratory epithelial inclusion cyst. Postoperatively, the vision improved and the hyperglobus resolved. The retinal striae and pigmentary disturbance persisted. Late capsule-related complications, such as epithelial cyst formation and intracapsular hemorrhage, have been reported in association with nonporous materials only. This case demonstrates that epithelial cyst formation may occur in association with a porous orbital floor implant and result in visual impairment.

Association of DAO and G72(DAOA)/G30 genes with bipolar affective disorder.

There is growing evidence of partial aetiological overlap between schizophrenia and bipolar disorder (BP) from linkage analysis, genetic epidemiology and molecular genetics studies. In the present study we investigated whether individual polymorphisms or haplotypes of the DAO and G72(DAOA)/G30 genes, which have been previously implicated in schizophrenia, are also associated with bipolar disorder. For each gene, we genotyped 213 cases and 197 controls for SNPs previously associated with schizophrenia: rs2111902 (MDAAO-4), rs3918346 (MDAAO-5), rs3741775 (MDAAO-6) and rs3918347 (MDAAO-7) in DAO and rs746187 (M7), rs3916966 (M13), rs2391191 (M15) and rs3916972 (M25) in G72. Although none of the individual SNPs in these genes reached statistical significance, we found haplotype wise associations with bipolar disorder for both genes. These included a two-SNP haplotype in DAO (rs2111902-A and rs3918346-T; global P = 0.003, individual P = 0.002, Z = 3.1) and a two-SNP haplotype for G72(DAOA)/G30 (rs746187-G and rs3916972-G; global P = 0.05; individual P = 0.005, Z = 2.81). However, we found no evidence for an epistatic interaction between the SNPs and/or haplotypes of the two genes. In summary, our findings provide some support for the individual involvement of DAO and G72(DAOA)/G30 in the etiology of bipolar disorder.

Association of the dysbindin gene with bipolar affective disorder.

OBJECTIVE: In the study of bipolar affective disorder and schizophrenia, there is some evidence suggesting a phenotypic and genetic overlap between the two disorders. A possible link between bipolar affective disorder and schizophrenia remains arguable, however. The authors hypothesized that dysbindin, which is a probable susceptibility gene for schizophrenia, was associated with bipolar affective disorder and tested this hypothesis using a case-control design study. METHOD: Participants included 213 patients with bipolar I disorder and 197 comparison subjects. In each subject, 10 polymorphisms in the dysbindin gene were genotyped and assessed. RESULTS: Two polymorphisms showed individual genotypic association with bipolar I disorder. Multiple marker haplotypes were more strongly associated, with the rarer of the two common haplotypes being overrepresented in the patients with bipolar affective disorder. A similar finding was reported in patients with schizophrenia in a previous study. CONCLUSIONS: Findings suggest that the human dysbindin gene may play a role in the susceptibility to bipolar affective disorder, which underscores a potentially important area of etiological overlap with schizophrenia. The existence of shared genetic risk factors will, in time, lead to changes in the current nosology of major psychoses.

Bipolar 1 disorder is not associated with the RGS4, PRODH, COMT and GRK3 genes.

Although current psychiatric nosology separates bipolar disorder and schizophrenia into non-overlapping categories, there is growing evidence of a partial aetiological overlap between them from linkage, genetic epidemiology and molecular genetics studies. Thus, it is important to determine whether genes implicated in the aetiology of schizophrenia play a role in bipolar disorder, and vice versa. In this study we investigated a total of 15 single nucleotide polymorphisms (SNPs), and all possible haplotypes, of genes that have been previously implicated in schizophrenia or bipolar disorder - RGS4, PRODH, COMT and GRK3 - in a sample of 213 cases with bipolar affective disorder type 1 and 197 controls from Scotland. We analysed the polymorphisms allele-wise, genotype-wise and, for each gene, haplotype-wise but obtained no result that reached nominal significance (p<0.05) for an association with the disease status. In conclusion, we could not find evidence of association between RGS4, PRODH, COMT and GRK3 genes and bipolar affective disorder 1 in the Scottish population.