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This chapter describes the current state of, and normative basis for, the law of reasonable royalties among the leading jurisdictions for patent infringement litigation, as well as the principal arguments for and against various practices relating to the calculation of reasonable royalties; and for each of the major issues discussed, the chapter provides one or more recommendations. The chapter’s principal recommendation is that, when applying a “bottom-up” approach to estimating reasonable royalties, courts should replace the Georgia-Pacific factors (and analogous factors used outside the United States) with a smaller list of considerations, specifically (1) calculating the incremental value of the invention and dividing it appropriately between the parties; (2) assessing market evidence, such as comparable licenses; and (3) where feasible and cost justified, using each of these first two considerations as a “check” on the accuracy of the other
Common bean (Phaseolus vulgaris L.) is perhaps the most important grain legume in sub-Saharan Africa (SSA) smallholder systems for food security and household income. Although a wide choice of varieties is available, smallholder farmers in western Kenya realize yields that are low and variable since they operate in risky production environments. Significant seasonal variations exist in rainfall and severity of pests and diseases. This situation is worsened by the low and declining soil fertility, coupled with low capacity of farmers to purchase production inputs such as fertilizers, fungicides and insecticides, and land scarcity. The objective of this study was to investigate whether growing multiple-bean varieties instead of a single variety can enable farmers enhance yield stability over seasons and ensure food security. Five common bean varieties were evaluated in multiple farms for 11 seasons at Kapkerer in Nandi County, western Kenya. Data were collected on grain yield, days to 50% flowering and major diseases. In addition, daily rainfall was recorded throughout the growing seasons. The five varieties were combined in all possible ways to create 31 single- and multiple-bean production strategies. The strategies were evaluated for grain yield performance and yield stability over seasons to determine the risk of not attaining a particular yield target. Results indicated that cropping multiple-bean varieties can be an effective way for reducing production risks in heterogeneous smallholder systems. Yield stability can be greatly enhanced across diverse environments, leading to improved food security, especially for the resource-poor smallholder farmers operating in risk-prone environments. Although the results show that some of the single-bean variety strategies were high yielding, their yield stability was generally lower than those of multiple strategies. Resource-poor risk averse farmers can greatly increase the probability of exceeding their yield targets by cropping multiple-bean varieties with relatively low yields but high grain yield stability. Trading-off high grain yield for yield stability might be an important strategy for minimizing bean production risks.
Environmental risk factors for dementia are poorly understood. Aluminium and fluorine in drinking water have been linked with dementia but uncertainties remain about this relationship.
In the largest longitudinal study in this context, we set out to explore the individual effect of aluminium and fluoride in drinking water on dementia risk and, as fluorine can increase absorption of aluminium, we also examine any synergistic influence on dementia.
We used Cox models to investigate the association between mean aluminium and fluoride levels in drinking water at their residential location (collected 2005–2012 by the Drinking Water Quality Regulator for Scotland) with dementia in members of the Scottish Mental Survey 1932 cohort who were alive in 2005.
A total of 1972 out of 6990 individuals developed dementia by the linkage date in 2012. Dementia risk was raised with increasing mean aluminium levels in women (hazard ratio per s.d. increase 1.09, 95% CI 1.03–1.15, P < 0.001) and men (1.12, 95% CI 1.03–1.21, P = 0.004). A dose-response pattern of association was observed between mean fluoride levels and dementia in women (1.34, 95% CI 1.28–1.41, P < 0.001) and men (1.30, 95% CI 1.22–1.39, P < 0.001), with dementia risk more than doubled in the highest quartile compared with the lowest. There was no statistical interaction between aluminium and fluoride levels in relation with dementia.
Higher levels of aluminium and fluoride were related to dementia risk in a population of men and women who consumed relatively low drinking-water levels of both.
Surgery for CHD has been slow to develop in parts of the former Soviet Union. The impact of an 8-year surgical assistance programme between an emerging centre and a multi-disciplinary international team that comprised healthcare professionals from developed cardiac programmes is analysed and presented.
Material and methods
The international paediatric assistance programme included five main components – intermittent clinical visits to the site annually, medical education, biomedical engineering support, nurse empowerment, and team-based practice development. Data were analysed from visiting teams and local databases before and since commencement of assistance in 2007 (era A: 2000–2007; era B: 2008–2015). The following variables were compared between periods: annual case volume, operative mortality, case complexity based on Risk Adjustment for Congenital Heart Surgery (RACHS-1), and RACHS-adjusted standardised mortality ratio.
A total of 154 RACHS-classifiable operations were performed during era A, with a mean annual case volume by local surgeons of 19.3 at 95% confidence interval 14.3–24.2, with an operative mortality of 4.6% and a standardised mortality ratio of 2.1. In era B, surgical volume increased to a mean of 103.1 annual cases (95% confidence interval 69.1–137.2, p<0.0001). There was a non-significant (p=0.84) increase in operative mortality (5.7%), but a decrease in standardised mortality ratio (1.2) owing to an increase in case complexity. In era B, the proportion of local surgeon-led surgeries during visits from the international team increased from 0% (0/27) in 2008 to 98% (58/59) in the final year of analysis.
The model of assistance described in this report led to improved adjusted mortality, increased case volume, complexity, and independent operating skills.
Contemporary ice stream flow is directly linked to conditions at the ice/bed interface, yet this environment is logistically difficult to access. Instead, we investigate subglacial processes important for ice stream flow by studying tills on the deglaciated Antarctic continental shelf. We test currently-accepted hypotheses surrounding subglacial processes and till properties with a Ross Sea dataset. Till shear strengths indicate a continuum of simultaneous processes acting at the bed, rather than discrete ‘deformation’ and ‘lodgement’ end-members. We identify a threshold water content representing saturated pore spaces, leading to basal sliding and meltwater channelization. Based on observations of till properties relative to glacial landforms, we challenge the assumption that low shear strength is linked to intense deformation. Spatial variability in landform morphology reflects variability in deforming processes at the sub-ice stream scale and suggests a maximum deforming bed thickness of 2 m at the grounding line. Regional till properties generally correlate with seafloor geology and deglacial history; the western Ross Sea is characterized by higher and more variable shear strengths and water contents, while lower-shear strength till was preserved in the Eastern Basin. These observations inform till interpretation and provide context for deforming beds beneath the modern ice sheet and on glaciated continental shelves.
There is increasing evidence for shared genetic susceptibility between schizophrenia and bipolar disorder. Although genetic variants only convey subtle increases in risk individually, their combination into a polygenic risk score constitutes a strong disease predictor.
To investigate whether schizophrenia and bipolar disorder polygenic risk scores can distinguish people with broadly defined psychosis and their unaffected relatives from controls.
Using the latest Psychiatric Genomics Consortium data, we calculated schizophrenia and bipolar disorder polygenic risk scores for 1168 people with psychosis, 552 unaffected relatives and 1472 controls.
Patients with broadly defined psychosis had dramatic increases in schizophrenia and bipolar polygenic risk scores, as did their relatives, albeit to a lesser degree. However, the accuracy of predictive models was modest.
Although polygenic risk scores are not ready for clinical use, it is hoped that as they are refined they could help towards risk reduction advice and early interventions for psychosis.
Declaration of interest
R.M.M. has received honoraria for lectures from Janssen, Lundbeck, Lilly, Otsuka and Sunovian.
Coinfection with human immunodeficiency virus (HIV) and viral hepatitis is associated with high morbidity and mortality in the absence of clinical management, making identification of these cases crucial. We examined characteristics of HIV and viral hepatitis coinfections by using surveillance data from 15 US states and two cities. Each jurisdiction used an automated deterministic matching method to link surveillance data for persons with reported acute and chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infections, to persons reported with HIV infection. Of the 504 398 persons living with diagnosed HIV infection at the end of 2014, 2.0% were coinfected with HBV and 6.7% were coinfected with HCV. Of the 269 884 persons ever reported with HBV, 5.2% were reported with HIV. Of the 1 093 050 persons ever reported with HCV, 4.3% were reported with HIV. A greater proportion of persons coinfected with HIV and HBV were males and blacks/African Americans, compared with those with HIV monoinfection. Persons who inject drugs represented a greater proportion of those coinfected with HIV and HCV, compared with those with HIV monoinfection. Matching HIV and viral hepatitis surveillance data highlights epidemiological characteristics of persons coinfected and can be used to routinely monitor health status and guide state and national public health interventions.
During the warmer Holocene Period, two major climatic crises affected the Central African rainforests. The first crisis, around 4000 cal yr BP, caused the contraction of the forest in favor of savanna expansion at its northern and southern periphery. The second crisis, around 2500 cal yr BP, resulted in major perturbation at the forest core, leading to forest disturbance and fragmentation with a rapid expansion of pioneer-type vegetation, and a marked erosional phase. The major driver of these two climatic crises appears to be rapid sea-surface temperature variations in the equatorial eastern Atlantic, which modified the regional atmospheric circulation. The change between ca. 2500 to 2000 cal yr BP led to a large increase in thunderstorm activity, which explains the phase of forest fragmentation. Ultimately, climatic data obtained recently show that the present-day major rise in thunderstorms and lightning activity in Central Africa could result from some kind of solar influence, and hence the phase of forest fragmentation between ca. 2500 to 2000 cal yr BP may provide a model for the present-day global warming-related environmental changes in this region.
Anthony M. Kwasnica, Smeal College of Business, The Pennsylvania State University,
John O. Ledyard, Division of the Humanities and Social Sciences, California Institute of Technology,
David P. Porter, Economic Science Institute, Chapman University,
Christine DeMartini, Division of the Humanities and Social Sciences, California Institute of Technology
Theory, experiment and practice suggest that, when bidder valuations for multiple objects are super-additive, combinatorial auctions are needed to increase efficiency, seller revenue, and bidder willingness to participate (Bykowsky et al. 2000, Rassenti et al. 1982, Ledyard et al. 2002). A combinatorial auction is an auction in which bidders are allowed to express bids in terms of packages of objects. The now famous FCC spectrum auctions are a good example of the relevance of these issues. In 41 auction events from 1994 to 2003, the FCC used what is known as a Simultaneous Multiple Round (SMR) auction to allocate spectrum and raise over $40 billion in revenue. This auction format does not allow package bidding. The FCC auctions also divide the spectrum by geographic location. It is reasonable to expect that some bidders might receive extra benefits by obtaining larger, more contiguous portions of the spectrum. A firm might enjoy cost savings if they could purchase two adjacent locations. However, without package bidding, a bidder cannot express that preference, potentially lowering the efficiency and revenue of the auction. If the bidder attempts to acquire both licenses through bidding on the licenses individually, they might be forced to expose themselves to potential losses. The high number of bidder defaults on payments might, in part, be evidence of losses caused by the lack of package bidding. In response to these difficulties, the FCC plans to allow package bidding in future auctions (Federal Communications Commission 2002, Dunford et al. 2001). In particular, the FCC in its auction #31 for the upper 700 MHz band, affords bidders the ability to submit bids for packages of licenses. The particular design presented in this paper was developed prior to the FCC package auction design. Indeed one of the major features of the FCC design was clearly influenced by the pricing rules we developed herein.
Field experiments were conducted in Louisiana and Mississippi from 2011 through 2013 to evaluate crop injury, weed control, and yield in field corn following pyroxasulfone applied PRE and POST. Pyroxasulfone PRE or POST did not injure corn at any evaluation. Barnyardgrass control was not improved with the addition of any POST treatment to pyroxasulfone alone or atrazine plus pyroxasulfone PRE; however, all POST treatments increased barnyardgrass control to at least 95% at all evaluations following atrazine PRE. All treatments that contained a PRE followed by POST application controlled browntop millet ≥90% at all evaluations. All POST treatments increased ivyleaf morningglory control to ≥92% following atrazine or pyroxasulfone alone PRE. However, control with atrazine plus pyroxasulfone PRE was similar or greater 28 d after POST than all treatments that received a POST application. In the absence of a POST treatment, pyroxasulfone or atrazine plus pyroxasulfone PRE controlled Palmer amaranth 93 to 96% at all evaluations, but atrazine alone PRE provided 84, 82, and 66% control 7, 14, and 28 d after POST, respectively. All programs that contained a PRE followed by POST herbicide treatment controlled Palmer amaranth >90% at all evaluations. Corn yield following all treatments except atrazine alone PRE and the nontreated were similar and ranged from 10990 to 12330 kg ha−1. This research demonstrated that pyroxasulfone can be a valuable tool for weed management in a corn weed management program.
Tabanids are haematophagous flies feeding on livestock and wildlife. In the absence of information on the relationship of tabanid flies and protozoan parasites in South Africa and Zambia, the current study was aimed at characterizing tabanid flies collected in these two countries as well as detecting protozoan parasites they are harbouring. A total of 527 tabanid flies were collected whereby 70·2% were from South Africa and 29·8% were from Zambia. Morphological analysis revealed a total of five different genera collected from the sampled areas namely: Ancala, Atylotus, Haematopota, Philoliche and Tabanus. DNA extracted from South African Tabanus par and Tabanus taeniola tested positive for the presence of Trypanosoma congolense (Savannah) and Trypanosoma theileri whilst one member from T. par was positive for Trypanosoma brucei species. DNA extracted from Zambian tabanid flies tested positive for the presence of Besnoitia species at 1·27% (2/157), Babesia bigemina 5·73% (9/157), Theileria parva 30·11% (30/157) and 9·82% (14/157) for Trypanosoma evansi. This study is the first to report on relationship of Babesia and Theileria parasites with tabanid flies. Further investigations are required to determine the role of tabanids in transmission of the detected protozoan parasites in livestock and wildlife in South Africa and Zambia.
Weed-free field experiments were conducted to evaluate soybean injury, growth, and yield following PRE or POST pyroxasulfone application. Soybean was injured 1 and 15% following pyroxasulfone PRE and POST application, respectively, 7 d after treatment (DAT). Injury following PRE and POST application was observed as delayed emergence and leaf necrosis and crinkling, respectively. Injury ranged from 0 to 6% following both application timings 14 and 28 DAT. Soybean was injured 5% or less following 60, 120, 180, 240, and 300 g ha−1 of pyroxasulfone. Soybean plant population, height, and yield were not affected by pyroxasulfone application timing. Only 300 g ha−1 of pyroxasulfone reduced soybean plant population to 90% of the nontreated 30 d after PRE. Pyroxasulfone rate did not influence soybean heights and yield. Data indicates that pyroxasulfone can safely be applied to soybean without a detrimental effect on plant growth or yield.
CHD is defined as structural defect(s) in the heart and proximal blood vessels present at birth. The National Cardiothoracic Center of Excellence, University of Nigeria Teaching Hospital (UNTH), Enugu, through the aid of visiting Cardiac Missions has managed a significant number of patients within the last 3.5 years.
The objective of this study was to review surgical options and outcome of complex CHD among patients attending UNTH, Enugu, Enugu.
Materials and Method
During the period of 3.5 years (March, 2013 to June, 2016), a total of 20 cases of complex CHD were managed by cardiac missions that visited UNTH, Enugu. Their case notes and operating register were retrieved, reviewed, and analysed using SPSS version 19 (Chicago).
There were eight females and 12 males, with a ratio of 2:5. The age range was from 5 months to 34 years with a mean of 1.7. Among all, five patients died giving a mortality rate of 25%. The operative procedures ranged from palliative shunts to complete repair. The outcome was relatively good.
Complex CHD are present in our environment. Their surgical management in our centre is being made possible by periodic visits of foreign cardiac missions.
The macular carotenoids lutein (L), zeaxanthin (Z) and meso-zeaxanthin (MZ) accumulate at the macula, where they are collectively referred to as macular pigment (MP). Augmentation of this pigment, typically achieved through diet and supplementation, enhances visual function and protects against progression of age-related macular degeneration. However, it is known that eggs are a rich dietary source of L and Z, in a highly bioavailable matrix. In this single-blind placebo-controlled study, L- and MZ-enriched eggs and control non-enriched eggs were fed to human subjects (mean age 41 and 35 years, respectively) over an 8-week period, and outcome measures included MP, visual function and serum concentrations of carotenoids and cholesterol. Serum carotenoid concentrations increased significantly in control and enriched egg groups, but to a significantly greater extent in the enriched egg group (P<0·001 for L, Z and MZ). There was no significant increase in MP in either study group post intervention, and we saw no significant improvement in visual performance in either group. Total cholesterol increased significantly in each group, but it did not exceed the upper limit of the normative range (6·5 mmol/l). Therefore, carotenoid-enriched eggs may represent an effective dietary source of L, Z and MZ, reflected in significantly raised serum concentrations of these carotenoids, and consequentially improved bioavailability for capture by target tissues. However, benefits in terms of MP augmentation and /or improved visual performance were not realised over the 8-week study period, and a study of greater duration will be required to address these questions.
Concerns relating to increased use of psychotropic medication contrast with those of under-treatment and under-recognition of common mental disorders in children and young people (CYP) across developed countries. Little is known about the indications recorded for antidepressant prescribing in primary care in CYP.
This was an electronic cohort study of routinely collected primary-care data from a population of 1.9 million, Wales, UK. Poisson regression was undertaken to model adjusted counts of recorded depression symptoms, diagnoses and antidepressant prescriptions. Associated indications were explored.
3 58 383 registered patients aged 6–18 years between 1 January 2003 and 31 December 2013 provided a total of 19 20 338 person-years of follow-up. The adjusted incidence of antidepressant prescribing increased significantly [incidence rate ratio (IRR) for 2013 = 1.28], mainly in older adolescents. The majority of new antidepressant prescriptions were for citalopram. Recorded depression diagnoses showed a steady decline (IRR = 0.72) while depression symptoms (IRR = 2.41) increased. Just over half of new antidepressant prescriptions were associated with depression (diagnosis or symptoms). Other antidepressant prescribing, largely unlicensed, was associated with diagnoses such as anxiety and pain.
Antidepressant prescribing is increasing in CYP while recorded depression diagnoses decline. Unlicensed citalopram prescribing occurs outside current guidelines, despite its known toxicity in overdose. Unlicensed antidepressant prescribing is associated with a wide range of diagnoses, and while accepted practice, is often not supported by safety and efficacy studies. New strategies to implement current guidance for the management of depression in CYP are required.
To evaluate a computer-assisted point-prevalence survey (CAPPS) for hospital-acquired infections (HAIs).
A 754-bed teaching hospital in the Netherlands.
For the internal validation of a CAPPS for HAIs, 2,526 patients were included. All patient records were retrospectively reviewed in depth by 2 infection control practitioners (ICPs) to determine which patients had suffered an HAI. Preventie van Ziekenhuisinfecties door Surveillance (PREZIES) criteria were used. Following this internal validation, 13 consecutive CAPPS were performed in a prospective study from January to March 2013 to determine weekly, monthly, and quarterly HAI point prevalence. Finally, a CAPPS was externally validated by PREZIES (Rijksinstituut voor Volksgezondheid en Milieu [RIVM], Bilthoven, Netherlands). In all evaluations, discrepancies were resolved by consensus.
In our series of CAPPS, 83% of the patients were automatically excluded from detailed review by the ICP. The sensitivity of the method was 91%. The time spent per hospital-wide CAPPS was ~3 hours. External validation showed a negative predictive value of 99.1% for CAPPS.
CAPPS proved to be a sensitive, accurate, and efficient method to determine serial weekly point-prevalence HAI rates in our hospital.
We present an overview of the survey for radio emission from active stars that has been in progress for the last six years using the observatories at Fleurs, Molonglo, Parkes and Tidbinbilla. The role of complementary optical observations at the Anglo-Australian Observatory, Mount Burnett, Mount Stromlo and Siding Spring Observatories and Mount Tamborine are also outlined. We describe the different types of star that have been included in our survey and discuss some of the problems in making the radio observations.
During routine monitoring of active-chromosphere stars in August 1987 an intense radio flare on the FK Comae star HD 32918 was detected by the Parkes radiotelescope. Other observatories were notified, enabling data to be collected at 843 MHz, 1.4 GHz, 8.4 GHz and optical frequencies.
The flare at radio frequencies was largely similar to a previous event on this star, reaching a peak radio power of 5 < 1012 W Hz−1 at 8.4 GHz. During the flare the spectrum varied as ∼ v1.4 and later flattened as the flare progressed. Compared to the previous flare, circular polarization was higher.
Ca II and Hα optical spectra taken at the AAO 3.9-metre telescope show the star to have a highly active chromosphere and a strong wind, with a terminal velocity of ≈230 km s−1. While much of this activity appears to be long lived, there is good evidence for an increase in the strength of the chromospheric lines during the radio flare event.
The subsurface exploration of other planetary bodies can be used to unravel their geological history and assess their habitability. On Mars in particular, present-day habitable conditions may be restricted to the subsurface. Using a deep subsurface mine, we carried out a program of extraterrestrial analog research – MINe Analog Research (MINAR). MINAR aims to carry out the scientific study of the deep subsurface and test instrumentation designed for planetary surface exploration by investigating deep subsurface geology, whilst establishing the potential this technology has to be transferred into the mining industry. An integrated multi-instrument suite was used to investigate samples of representative evaporite minerals from a subsurface Permian evaporite sequence, in particular to assess mineral and elemental variations which provide small-scale regions of enhanced habitability. The instruments used were the Panoramic Camera emulator, Close-Up Imager, Raman spectrometer, Small Planetary Linear Impulse Tool, Ultrasonic drill and handheld X-ray diffraction (XRD). We present science results from the analog research and show that these instruments can be used to investigate in situ the geological context and mineralogical variations of a deep subsurface environment, and thus habitability, from millimetre to metre scales. We also show that these instruments are complementary. For example, the identification of primary evaporite minerals such as NaCl and KCl, which are difficult to detect by portable Raman spectrometers, can be accomplished with XRD. By contrast, Raman is highly effective at locating and detecting mineral inclusions in primary evaporite minerals. MINAR demonstrates the effective use of a deep subsurface environment for planetary instrument development, understanding the habitability of extreme deep subsurface environments on Earth and other planetary bodies, and advancing the use of space technology in economic mining.
There are striking global inequities in our knowledge of the incidence, aetiology, and outcome of psychotic disorders. For example, only around 10% of research on incidence of psychotic disorders originates in low- and middle-income countries. We established INTREPID I to develop, implement, and evaluate, in sites in India (Chengalpet), Nigeria (Ibadan), and Trinidad (Tunapuna-Piarco), methods for identifying and recruiting untreated cases of psychosis, as a basis for investigating incidence and, subsequently, risk factors, phenomenology, and outcome. In this paper, we compare case characteristics and incidence rates across the sites.
In each site, to identify untreated cases of psychoses in defined catchment areas, we established case detection systems comprising mental health services, traditional and spiritual healers, and key informants.
Rates of all untreated psychoses were 45.9 (per 1 00 000 person-years) in Chengalpet, 31.2 in Ibadan, and 36.9 in Tunapuna-Piarco. Duration of psychosis prior to detection was substantially longer in Chengalpet (median 232 weeks) than in Ibadan (median 13 weeks) and Tunapuna-Piarco (median 38 weeks). When analyses were restricted to cases with a short duration (i.e. onset within preceding 2 years) only, rates were 15.5 in Chengalpet, 29.1 in Ibadan, and 26.5 in Tunapuna-Piarco. Further, there was evidence of age and sex differences across sites, with an older average age of onset in Chengalpet and higher rates among women in Ibadan.
Our findings suggest there may be differences in rates of psychoses and in the clinical and demographic profiles of cases across economically and socially distinct settings.