Formal verification of OIL component specifications using mCRL2

International Journal on Software Tools for Technology Transfer - To aid in making software bug-free, several high-tech companies are moving from coding to modelling. In some cases model checking...     

Coupling granule properties and granulation rates in high-shear granulation

It is possible to link granulation rates to granule properties. The linkage is by multiple dimension population balance equations that, by means of simplifying assumptions, can be reduced to multiple one-dimensional (1-D) population balance equations (PBEs). Using simple physically based models, this paper demonstrates how multiple one-dimensional population balance equations can describe the results of high-shear granulation experiments of two different materials, calcium carbonate and lactose. Good agreement between experimental and simulated results was achieved enabling the granulation rates to be defined by two model parameters: the critical binder volume fraction and the aggregation rate constant. The modelling framework presented in this paper also provides a basis for the kinetic analysis of granulation experiments so that with further work, it is possible to determine the effect of process conditions and material properties on the model parameters.     

The onset of the ovarian cycle following calving

The onset of ovarian activity post partum was investigated by measuring progesterone concentrations in milk samples, in two dairy herds consisting of 118 cows with an average milk yield of 8340 kg FCM. Samples were taken three times a week till 50 days post partum. In 17 cows (14.4%) anoestrus occurred. The daily milk yield in this group was 2.65 kg FCM higher than the average yield in the group returning to oestrus before day 50 post partum. In cows returning to oestrus within 50 days post partum the first rise in progesterone was detected on average 27.6 days after calving. In first calvers (31.4 +/- 10.2) and in multiparous cows in the winter period (26.9 +/- 9.4) the onset of ovarian activity was delayed compared to start of ovarian activity in the summer period. In the first cycle only 28% of the cows had a normal luteal phase (12-17 days), 36% of the cows had a shortened luteal phase (less than 6 days), and 24% of the cows had a short luteal phase (6-11 days). In 12% of the cows the luteal phase was longer than 17 days. In the second cycle 56% of the cows had a normal luteal phase while 17% had a shortened luteal phase, and 17% had a short luteal phase. Pregnancy rates after first insemination in cows with a short dioestrus (10-25 days) were higher than in cows with a prolonged dioestrus (26-50 days). On the basis of these result it might be expected that postponing the first insemination until the second or even the third cycle in high-yielding cows will have only a marginal effect on the number of open days and a large effect on the number of inseminations per pregnancy.     

Randomized trial of recombinant human interleukin-3 versus placebo in prevention of bone marrow depression during first-line chemotherapy for ovarian carcinoma

PURPOSE: To determine whether recombinant human interleukin-3 (rhIL-3) reduces bone marrow depression and improves chemotherapeutic schedule adherence in ovarian cancer patients receiving first-line combination chemotherapy. PATIENTS AND METHODS: In a randomized multicenter study, 185 patients received carboplatin (dose based on projected area under the concentration-time curve [AUC]=4) and cyclophosphamide (750 mg/m2) day 1, every 3 weeks for six cycles. Patients were randomized to receive rhIL-3 (5 microg/kg) or placebo once daily subcutaneously on days 3 to 12. RESULTS: Adherence to chemotherapeutic regimen, mean chemotherapy cycle length, tumor response rate, and median survival at 24 months did not differ between groups. The number of side effects-primarily allergic reactions, flu-like symptoms and fever-were higher in the rhIL-3 group, which resulted in 21 discontinuations compared with one in the placebo group. Compared with placebo, the rhIL-3 group had higher platelet counts day 1 of cycles 2 to 6. The number of patients with World Health Organization (WHO) grade IV thrombocytopenia or number of platelet transfusions did not differ. Leukocyte counts differed only in cycles 1 and 2 between groups. The leukocyte nadir occurred earlier in the rhIL-3 (day 12) than in the placebo group (day 15, P=.006). Leukocytes and neutrophils were only higher in the rhIL-3 group day 1 of cycle 2. In cycles 4 and 5, more patients with WHO grade IV neutropenia received rhIL-3 (P < .005). Eosinophil counts were higher day 1 of cycles 2 to 6 in the rhIL-3 group (P < .0001). CONCLUSION: rhIL-3 had stimulatory hematopoietic effects. This did not result either in reduction of platelet transfusions or in improvement of chemotherapeutic schedule adherence. There were more side effects in the rhIL-3 group than in the placebo group. rhIL-3 at 5 microg/kg/d is, therefore, not of clinical benefit in this chemotherapeutic regimen.     

Value of transcranial Doppler indices in predicting raised ICP in infantile hydrocephalus. A study with review of the literature

Cerebral hemodynamic changes in infants with progressive hydrocephalus have been studied with the transcranial Doppler (TCD) technique. Several authors have referred to the correlation between the hemodynamic changes and increased intracranial pressure (ICP). Despite conflicting conclusions on the value of pulsatility index (PI) and resistance index (RI) measurements for monitoring infantile hydrocephalus, these pulsatility indices are the most commonly used for this purpose. Although clinical signs of raised ICP are highly variable and unreliable in infants, assumptions have been made in most of the studies about the presence of elevated ICP on the basis of the patient's clinical state. Few studies have reported on actual ICP values, however, and a direct relationship between ICP and TCD changes has never been adequately demonstrated. In the present study, this relationship was investigated in long-term simultaneous TCD/ICP measurements, in an attempt to develop a noninvasive method of monitoring the effect of ICP on intracranial hemodynamics. Two groups of data sets were established. Group I consisted of pre- and postoperative (shunt implantation) TCD/ICP measurements. Group II were long-term simultaneous TCD/ICP recordings showing significant ICP variations. In most of the postoperative measurements there was a decrease in the average PI and RI values. The correlation between PI or RI and ICP in the long-term simultaneous recordings, however, was generally poor. The risk of obtaining false positive or false negative PI or RI values in short-term measurements was also demonstrated. It can be concluded from our results, besides the wide range of reference values for the Doppler indices and extracranial influences upon them, that the present Doppler indices are inadequate for monitoring the complex intracranial dynamic responses in patients with raised ICP.     

Actual versus Predicted Transboundary Impact: A Case Study of Phase 1B of the Lesotho Highlands Water Project

The Lesotho Highlands Water Project was initiated in 1986 as a result of discussions between the governments of the Kingdom of Lesotho and the Republic of South Africa (SA) that, together with feasibility studies, had commenced in the early 1950s. The project targeted the Senqu River, which originates in the Lesotho Highlands, merges with the Orange River in South Africa, and drains into the Atlantic Ocean, creating a natural border between Namibia and South Africa. Four riparian states, including Botswana, rely heavily on the Sengu's water for development. The multi-donor billion-dollar project consisted of two initial phases, 1A and 1B. No impact assessment was conducted for Phase 1A. As a result of international critique, lessons learned and the involvement of the World Bank, Phase 1B considered all possible environmental, social and economic impacts. The full-scale EIA recognized, but did not fully consider, transboundary impacts, which were only addressed through the commissioning of an In-stream Flow Requirement (IFR) study in 2000, once the project commenced.     

Impact of cerebral visual impairment on the everyday life of cerebral palsied children

A group of 43 patients suffering from cerebral palsy and cerebral visual impairment was compared with a group of 24 cerebral palsy patients with normal visual acuity, with regard to a functional level in daily life. Four categories were considered: communication, emotional contact, self-care and intelligence. Cerebral visual impairment-cerebral palsy patients scored significantly lower in all categories than cerebral palsy patients with normal visual acuity. In the cerebral visual impairment-cerebral palsy group, there was a higher frequency of tetraplegia compared with the group with normal acuity, but even after this predominance had been excluded, a significant difference remained. When dealing with cerebral palsy patients, occurrence of cerebral visual impairment must be taken into account. By initiating intervention programmes, one can prevent extra handicaps due to the consequences of diminished visual acuity.     

Hypertensive encephalopathy in childhood. Diagnostic problems

Oppenheimer and Fischberg's vasoconstriction-hypothesis on the pathogenesis of hypertensive encephalopathy was subsequently supported by animal experiments. Later on the role of decompensation of the autoregulatory mechanism of the cerebral blood flow was revealed. The transient symptomatology comprises headache, seizures, focal cerebral symptoms (hemiplegia etc.), visual disturbances, mental disorders, papiledema etc. The age-dependency of the influence of edema is probably expressed by the predominance of seizures in childhood and the long duration of the symptoms in our third and fourth patient. The differentiation between hypertensive encephalopathy and a local complication of hypertension (hemorrhage) can be difficult, not at least because the first disturbance may be followed by the second (patient 3). Hypertension is not always present as initial symptom (patient 1 and 2). Hence a series of blood pressure readings is required in acute cerebral incidents in childhood. Steroid-treatment may lead, especially in patients suffering from a hypocomplementemic form of membranoproliferative glomerulonephritis, to a sudden rise of the blood pressure and subsequently to hypertensive encephalopathy (patients 2 and 3). Hypertensive encephalopathy is a neuropediatric emergency. The urgent treatment with dioxaside, fursemide and sodium nitroprusside is shortly reviewed.