Background:ATP8A2 mutations have only recently been associated with human disease. We present the clinical features from the largest cohort of patients with this disorder reported to date. Methods: An observational study of 9 unreported and 2 previously reported patients with biallelic ATP8A2 mutations was carried out at multiple centres. Results: The mean age of the cohort was 9.4 years old (range: 2.5-28 yrs). All patients demonstrated developmental delay, severe hypotonia and movement disorders: chorea/choreoathetosis (100%), dystonia (27%) or facial dyskinesia (18%). Hypotonia was apparent at birth (70%) or before 6 months old (100%). Optic atrophy was observed in 75% of patients who had a funduscopic examination. MRI of the brain was normal for most patients with a small proportion showing mild cortical atrophy (30%), delayed myelination (20%) and/or hypoplastic optic nerves (20%). Epilepsy was seen in two older patients. Conclusions:ATP8A2 gene mutations have emerged as a cause of a novel phenotype characterized by developmental delay, severe hypotonia and hyperkinetic movement disorders. Optic atrophy is common and may only become apparent in the first few years of life, necessitating repeat ophthalmologic evaluation. Early recognition of the cardinal features of this condition will facilitate diagnosis of this disorder.

This paper addresses the problem of designing low-order and linear robust feedback controllers that provide a priori guarantees with respect to stability and performance when applied to a fluid flow. This is challenging, since whilst many flows are governed by a set of nonlinear, partial differential–algebraic equations (the Navier–Stokes equations), the majority of established control system design assumes models of much greater simplicity, in that they are: firstly, linear; secondly, described by ordinary differential equations (ODEs); and thirdly, finite-dimensional. With this in mind, we present a set of techniques that enables the disparity between such models and the underlying flow system to be quantified in a fashion that informs the subsequent design of feedback flow controllers, specifically those based on the $\mathscr{H}_{\infty }$ loop-shaping approach. Highlights include the application of a model refinement technique as a means of obtaining low-order models with an associated bound that quantifies the closed-loop degradation incurred by using such finite-dimensional approximations of the underlying flow. In addition, we demonstrate how the influence of the nonlinearity of the flow can be attenuated by a linear feedback controller that employs high loop gain over a select frequency range, and offer an explanation for this in terms of Landahl’s theory of sheared turbulence. To illustrate the application of these techniques, an $\mathscr{H}_{\infty }$ loop-shaping controller is designed and applied to the problem of reducing perturbation wall shear stress in plane channel flow. Direct numerical simulation (DNS) results demonstrate robust attenuation of the perturbation shear stresses across a wide range of Reynolds numbers with a single linear controller.

After stressing the importance of the plant kingdom to Man and the dangers threatening the survival of an estimated 20,000 species of flowering plants, this paper presents details of the activities of the IUCN Threatened Plants Committee (TPC), set up by the Survival Service Commission in 1974. The Secretariat of the TPC works through three main approaches: (1) regional groups of botanists and other experts identifying threats to their floras, advising the TPC, and preparing recommendations; (2) specialist groups doing similar work for plant groups such as palms and cycads; and (3) institutional support of botanic gardens and similar organizations maintaining collections of threatened species in cultivation. This last aspect was launched at a conference on conservation held at Kew in 1975.

The primary aim of the TPC is to gather and disseminate information on which species are threatened throughout the world. Accurate documentation is essential, and in this task both herbarium and field work are needed. Although our knowledge in general of temperate, subtropical, and islands, floras is reasonably good in most cases, and there are specialists working on most of such areas, our knowledge of continental tropical floras is much less comprehensive. There is an urgent need for check-lists to be rapidly compiled for such areas wherever possible. In tropical rain-forests, the difficulties encountered in listing threatened species are particularly acute.

Provided present collaboration continues and finance is provided, initial lists of rare and threatened species will become available within the next decade for many areas. This information should be of great value in preventing needless extinction through lack of planning or forethought, in providing a valuable input in the selection of sites for reserves, etc., and in complementing habitat conservation approaches—as well as helping to stimulate action on individual species.

The ‘Red Data’ categories used by IUCN to indicate the degrees of threat to individual species are outlined, and will be used in the three types of TPC publication—regional lists of rare and threatened species, bulletins on smaller areas with more detail on each species, and sheets for the Red Data Book which will give detailed case-histories of a limited selection of threatened species. All three approaches are under way; the European List has been completed, bulletins for many areas are on the way, and the TPC aims to start issuing new plant Red Data sheets in 1977–78.

1. This report continues the account of the experimental field work carried out by the Tsetse Investigation in Northern Nigeria from May 1926 up to the end of 1929. G. morsitans and G. tachinoides are the tsetse concerned. The main object of this work was to attempt to control tsetse by the destruction of primary and secondary foci by the clearing of all fringing forest, the general woodland being left untouched. Two main experimental areas have been dealt with, the Sherifuri area described previously and the Matyoro experimental area.

2. Methods of clearing and dealing with re-growth are described in detail. Records show that re-growth although very rapid the first year, then slows down to such an extent that it may not be economical to re-slash more often than every third year. The effect of clearing on tsetse was controlled by collecting fly week by week from certain fixed foci. These flies were dissected and the following factors noted : the sex proportion in the catch, the rate of catching, the state of nutrition, the proportion of very young flies, the blood content of the gut with classification of the kinds of blood found, and the trypanosome infection.

With G. morsitans, clearing of fringing forest only up to 800 yards from the collecting centre had no apparent effect on the wet season extension but at four miles it was reduced to one-sixth of its old figure.

(1) This report is an account of the experimental work carried out by the Tsetse Investigators in Northern Nigeria during the period from January 1924 to May 1926. G. morsitans and G. tachinoides are dealt with. In the Introduction the district around Sherifuri, where the camp is situated, is described, the differences between primary and secondary tsetse foci are defined, and an account is given of the method of collecting data as a basis on which to estimate the effects of experiment. Before and during experiment flies were collected week by week from foci subject to experimental change and from others employed as controls, the following factors being noted : the sex proportion in the catch, the rate of catching, the state of nutrition, the proportion of very young flies, the blood content of the guts with classification of the kinds of blood taken, and the trypanosome infection.

(2) An experiment was carried out in which game was excluded from a good secondary focus of tsetse by means of a fence. This set up a state of starvation in morsitans and to some extent in tachinoides. There was a marked reduction in the abundance of both species, especially in morsitans. More blood than usual was taken by morsitans from birds, and both species contained a larger proportion of blood of human type than is usual. Invasion of the enclosed area by tsetse from outside vitiated the experiment and resulted in certain anomalies, viz., that the rate of trypanosome infection remained high ; the blood content was not appreciably decreased ; the proportion of very young flies increased abnormally in morsitans. It is considered that game destruction, if it could be accomplished, would lead to a disappearance of morsitans, but not of tachinoides, and for this reason no policy of game destruction is recommended, but a policy of laissez faire towards the game in Northern Nigeria, so that there may be no increase in the wild Ungulata, which results in increase and spread of fly.

(3) A successful experiment in deferred grass burning is recounted. The late sweeping fire resulted in a great mortality of morsitans and tachinoides, both flies and pupae. It hardly affected the growth of established thicket, but probably checked expansion of such and the formation of new thicket. It is considered that late grass fires, well organised, might have a good effect in Northern Nigeria, but the difficulties in the way of postponement of burning are exceedingly great in this country.

(4) The commencement of an experiment in clearing with subsequent settlement is briefly described. Except on the main road through the experimental area only fringing forest is being cut down, the general woodland being left untouched. If this policy is successful only a relatively small proportion of a fly area will need to be cleared, attention being confined to the main foci.

(5) An account is given of an unsuccessful attempt to introduce into Nigeria Syntomosphyrum glossinae, a Chalcid parasite of G. morsitans in East Africa.

(1) The salivary glands of Glossina contain a powerful anticoagulin, which delays the clotting of blood of mammals, birds, reptiles and batrachians. It was found that when the salivary glands are removed from the living fly, it can still draw blood normally and may live long, but sooner or later large clots form in the narrow anterior portions of the alimentary tract, so that the fly can no longer feed and dies of starvation. The purpose of the anticoagulin is to prevent such clotting and blood coagulation in the crop.

(2) The proventriculus and first third of the mesenteron are themselves inert in relation to coagulation of blood, but as removed from the normal fly they contain the anticoagulin which is derived from the salivary secretion.

(3) The hinder part of the mesenteron contains a powerful coagulin, the purpose of which is to neutralise the anticoagulin and cause a rapid clotting, in order to retain the fluid meal in the proper region while draining and assimilation take place, probably also to save strain on the sphincter mesenteri and prevent the occasional loss of food through the anus.

The reproductive performance of breeding and cyclic Welsh Mountain (WM) and Border Leicester (BL) ewes was compared in two contrasting photoperiodic environments during January 1971–April 1972. Treatment 1 consisted of natural daylength changes at latitude 51° 43’ N. There was no difference between the two breeds in onset of the breeding season, percentage exhibiting oestrus or percentage lambing. The breeding season of BL ewes terminated earlier (mean date, 31 January) than that of WM ewes (mean date, 9 March). The WM ewes had 8–12 oestrous periods and the BL ewes 7–11 oestrous periods. In treatment 2 a simulated equatorial photoperiod (13 h light: 11 h dark) was applied from January 1971 but was inadvertently interrupted by a short period of continuous light in June 1971. All WM ewes exhibited oestrus compared with 37·5% of BL ewes. The failure to show oestrus in the majority of BL ewes contributed to the marked difference between breeds in the percentage of ewes lambing: 88·9% in WM compared with 11·1% in BL ewes. In the cyclic subgroup, the WM ewes had 3–10 oestrous periods and the BL ewes, 2–7 oestrous periods.

It is concluded that the breeds showed a differential response to the two treatments and that Treatment 2 had a marked adverse effect on the reproductive potential of the Border Leicester ewes.

A low sodium diet was given to Scottish Blackface ewes over two reproductive seasons. It provided a total of 3–7 mmol sodium per day, except during lactation when the intake was about 11 mmol sodium per day. Control ewes were given the same diet supplemented with sodium chloride to Agricultural Research Council recommended concentration which was about ten times greater than that in the experimental diet.

The ewes remained clinically healthy throughout the experiment. The length of gestation and the birth weight of lambs were unaffected by diet. The number of lambs born alive per ewe lambing was unaffected by year or diet.

The percentage of ewes producing twins was similar in control ewes in both years at about 64; in treatment ewes this was 70% in year 1, and 50% in year 2. Lamb mortality was higher in both years in the treatment ewes than in control ewes. None of these differences reached significance.

The effects of two, symmetrically opposing, light treatments on the semen of Suffolk rams were investigated over two years. The light rhythm had an amplitude of 12 h and a cycle of 24 weeks. Data on semen volume, spermatozoa concentration, total spermatozoa per ejaculate, fructose concentration, seminal fluid fructose concentration and total fructose were collected during 38 semen collection periods. During the last 20 periods libido was assessed on the interval to mounting.

The effects of treatments were assessed by fitting Fourier curves with 24-week cycles to the observed fluctuation of the differences between treatments and with 52-week cycles to the means of treatments. From periodic regression analysis of the treatment differences it is concluded that the Suffolk rams were susceptible to the artificial light rhythms and that both groups adapted to the imposed rhythms. Some effects of the pretreatment photic environment appeared to persist during the first year of the treatment period. There appeared to be a lag between the fluctuations of the semen attributes resulting in a series of sequential changes.

Border Leicester ewes were kept in three contrasting photoperiodic environments, the rhythm at latitude 30° 32′ S (group 1) - 12 h light: 12 h dark interrupted by 6 weeks of continuous light (group 2a) and 12 h light: 12 h dark (group 2b) - from August 1972 to September 1973. In group 1 all ewes exhibited oestrus compared with 87·5% and 57·1% in groups 2(a) and 2(b) respectively. The mean number of oestrous periods per ewe ranged from 4·4 in group 1 to 3·0 in group 2(a) and 1·0 in group 2(b). It is concluded that the non-fluctuating light rhythm had an adverse effect on the reproductive potential of the treated groups and that Border Leicester ewes are dependent on a fluctuating light rhythm for normal reproductive function.

1. The problem discussed is the temperature distribution in a semi-infinite solid, initially at zero, when the surface is suddenly raised to and maintained at a temperature which is an arbitrary function of the distance from some line which lies in that surface.

In order to understand better the factors which influence the persistence or non-persistence of Lolium perenne and Trifolium repens on damp hill land in a wet climate, swards in mid-Wales which had been converted from semi-natural rough grazing (predominantly Molinia caerulea or Nardus stricta or Agrostis/Festuca/Nardus) in 1961–81 were examined in 1982 and 1999, using a point quadrat technique.

There was a marked decline between 1982 and 1999 in the proportion of L. perenne in the majority of the study areas. On the other hand, in 1999 the oldest swards (sown 30–38 years before) contained at least as high a proportion of L. perenne (22% of sward on average) as the younger swards (sown 18–29 years before). In two swards sown 25–26 years before, at 390–445 m above sea level, which received 95 kg N/ha per year, L. perenne was 36% of sward. On the other hand, no L. perenne was recorded on three swards which were no longer receiving fertilizer and which were being grazed at a greatly reduced stocking rate. The proportion of T. repens was rather low and declined between 1982 and 1999 (from 10 to 4% of sward on average). The application of more lime and more K and perhaps less N would probably have increased the proportion of T. repens. On at least one farm, the use of MCPA against Cirsium spp. had probably reduced the proportion of T. repens. There were positive correlations between the proportion of L. perenne and the proportions of T. repens and Poa spp. There were negative correlations between L. perenne and each of Agrostis spp., Festuca spp. and Holcus lanatus and also between T. repens and Agrostis spp. The proportion of Poa spp. was positively correlated with exchangeable Ca, nitrate-N and total N in soil and negatively correlated with exchangeable acidity.

The local structure of homomorphisms of commutative noetherian rings is investigated from the point of view of dualizing complexes. A concept of finite Gorenstein dimension, which substantially weakens the notion of finite flat dimension, is introduced for homomorphisms. It is shown to impose structural constraints, due to a remarkable equivalence of subcategories of the derived category of all modules.

An essential part of this study is the development of relative notions of dualizing complexes and Bass numbers. It is proved that the Bass numbers of local homomorphisms are rigid, extending a known result for local rings. Quasi-Gorenstein homomorphisms are introduced as local homomorphisms that base-change a dualizing complex for the source ring into one for the target. They are shown to have the stability properties of the Gorenstein homomorphism that they generalize.

1991 Mathematics Subject Classification: primary 13H10, 13D23, 14E40; secondary 13C15.

Three types of high glucosinolate British rapeseed meal (RSM) — extracted, expeller and extruded — were incorporated in ewe diets at 200 g/kg; soya-bean meal (SBM) at 165 g/kg replaced RSM in a control diet. Eighty housed Suffolk-Mule ewes were divided into four equal groups and given one of four diets, A (control SBM), B (extracted RSM), C (expeller RSM) or D (extruded RSM) for one reproductive cycle. Diets A and B were compared for a second season. The ewes were given a maximum of 2·5 kg diet per day during lactation. Barley straw was available ad libitum. The ewes were mated in November and December. Lambs were weaned at 42 days of age; they were given creep food similar in composition to their dams' lactation diets.

There were no dietary effects on ewes in overall health, live weight, oestrous activity, conception, number of lambs born alive or lamb birth weights. A mean of 1·6 lambs were weaned per ewe mated and 58% of these were twins, in year 1. In year 2, 1·8 lambs were reared and 79% were twins. The mean milk yield over the first 4 weeks of lactation was 3·2 1 and there were no significant dietary effects. Fat concentration in milk was very variable, but in general was slightly depressed by the RSM diets, significantly so at three sampling dates. Protein concentration was consistently lower in milk from RSM than SBM groups, significantly lower at four of the weekly samplings. Thiocyanate levels in plasma and milk were related to glucosinolate intake, but were not associated with any detrimental effects. At all sampling dates, values for RSM groups were significantly greater than for SBM ewes. Plasma thyroxine values were similar regardless of diet

The response of Hereford × Friesian heifers to large intakes of two types of high glucosinolate rapeseed meal were studied during two 5-month periods in consecutive years. In year 1, six heifers were given a compound concentrate food containing 250 g/kg extracted rapeseed meal and six control animals were given concentrate containing 210 g/kg soya-bean meal. In year 2, a further six heifers were given concentrate containing 320 g/kg expeller rapeseed meal and six control animals were given the same soya-bean meal compound concentrate. The crude protein (CP): metabolizable energy (ME) ratio of all diets was 14·3 g CP per MJ ME. Barley straw was the only roughage offered.

There were no differences between groups in ovarian activity assessed from plasma progesterone concentrations, nor in behavioural activity around oestrus. The heifers were slaughtered 6 weeks after artificial insemination. Pregnancy rate was proportionally 0·58 (7/12) in the rape-fed and 0·67 (8/12) in the control heifers (P > 0·05). Foetuses from heifers given rapeseed meal were slightly smaller than those from control heifers; the difference was significant in year 2 (P < 0·05).

Thyroid glands of heifers given rapeseed meal showed histological evidence of goitrogenicity but weights of the glands did not reflect this. Plasma thyroxine values were depressed in heifers given rapeseed meal (year 1, P < 0·001; year 2, P < 0·05). Plasma thiocyanate was elevated in rapeseed meal heifers in both years (P < 0·001) compared with values for control animals.

1. A low-sodium diet was given to Blackface ewes over two reproductive seasons. This diet provided a total of 3–7 mmol/d except during lactation when the intake was about 11 mmol/d. Control ewes were given the same diet supplemented with sodium chloride to provide recommended levels which were about tenfold that of the experimental diet.

2. The output of Na in urine and faeces from ewes given the low-Na diet was very low, about 3 mmol/d, from early in the experiment and continued at about this level throughout.

3. Lambs born to low-Na ewes and given a low-Na diet similar to that of their dams during lactation, grew, after weaning, more slowly than corresponding lambs from control ewes, but at 6 months of age when six from each group were killed, tissue Na contents were only slightly lower in experimental than control lambs.

4. Fluids and tissues obtained at the end of the second lactation from four ewes of each group that had suckled twin lambs, were analysed for Na and potassium. The Na concentration in saliva and rumen fluid of low-Na ewes was about half that of control ewes and there were corresponding increases in K: the differences were significant. Although Na concentrations for experimental ewes were generally lower than those for control ewes in the tissues analysed (liver, kidney, heart, brain and bone), the difference was significant only for the heart (P < 0.05). Haemoglobin and packed cell volume were significantly elevated in low-Na ewes (P < 0.01), indicating decreased body fluid volume. Enlargement of the adrenal glands in low-Na ewes (P < 0.01) and specifically in the zona glomerulosa (P < 0.001), showed the marked hormonal response to Na status of experimental ewes given a very-low-Na diet over two reproductive cycles.

1. A low-sodium diet was given to Blackface ewes over two reproductive seasons; the diet provided 3–7 mmol Na daily, except for the period of lactation, when Na intake was increased to around 11 mmol/d. The diet of the control ewes was supplemented with sodium chloride to provide the recommended allowance of about ten times the level in the experimental low-Na diet.

2. Milk production was assessed during the first 2 months of lactation from incremental changes in the live weight of lambs during controlled sucking periods. Na and potassium were determined in milk and also in plasma, saliva and urine.

3. Neither yield nor concentration of Na and K in milk was affected by the level of Na in the diet. These results were supported by the similarity in live-weight gain of lambs in both years regardless of diet.

4. Plasma Na and K concentrations were not affected by the level of dietary Na. Na concentration in saliva and urine was significantly lower in the treated than in the control ewes, and K concentration in saliva was significantly higher.