Use of apomorphine in Parkinsonian patients with neuropsychiatric complications to oral treatment

Neuropsychiatric side effects often complicate anti-Parkinsonian therapy and pose a significant problem in the optimal management of idiopathic Parkinson's disease. Several publications report a relative lack of neuropsychiatric side effects in Parkinsonian patients treated with subcutaneous apomorphine. To investigate this further, we have used subcutaneous apomorphine to treat 12 non-demented IPD patients with previous oral drug-related neuropsychiatric problems. Treatment with apomorphine allowed alteration of anti-Parkinsonian medication and led to the abolition or reduction of neuropsychiatric complications in all patients. The mechanism remains unclear but may be due, in part, to a reduction in oral medication or a psychotropic action of apomorphine, possibly due to the piperidine moiety in its structure, or both

Collective physician perspectives on non-oral medication approaches for the management of clinically relevant unresolved issues in Parkinson's disease: Consensus from an international survey and discussion program

Navigate PD was an educational program established to supplement existing guidelines and provide recommendations on the management of Parkinson's disease (PD) refractory to oral/transdermal therapies. It involved 103 experts from 13 countries overseen by an International Steering Committee (ISC) of 13 movement disorder specialists. The ISC identified 71 clinical questions important for device-aided management of PD. Fifty-six experts responded to a web-based survey, rating 15 questions as ‘critically important;’ these were refined to 10 questions by the ISC to be addressed through available evidence and expert opinion. Draft guidance was presented at international/national meetings and revised based on feedback. Key take-home points are: • Patients requiring levodopa >5 times daily who have severe, troublesome ‘off’ periods (>1–2 h/day) despite optimal oral/transdermal levodopa or non-levodopa-based therapies should be referred for specialist assessment even if disease duration is <4 years. • Cognitive decline related to non-motor fluctuations is an indication for device-aided therapies. If cognitive impairment is mild, use deep brain stimulation (DBS) with caution. For patients who have cognitive impairment or dementia, intrajejunal levodopa infusion is considered as both therapeutic and palliative in some countries. Falls are linked to cognitive decline and are likely to become more frequent with device-aided therapies. • Insufficient control of motor complications (or drug-resistant tremor in the case of DBS) are indications for device-aided therapies. Levodopa-carbidopa intestinal gel infusions or subcutaneous apomorphine pump may be considered for patients aged >70 years who have mild or moderate cognitive impairment, severe depression or other contraindications to DBS

Relic Neutralino Densities and Detection Rates with Nonuniversal Gaugino Masses

We extend previous analyses on the interplay between nonuniversalities in the gaugino mass sector and the thermal relic densities of LSP neutralinos, in particular to the case of moderate to large tan beta. We introduce a set of parameters that generalizes the standard unified scenario to cover the complete allowed parameter space in the gaugino mass sector. We discuss the physical significance of the cosmologically preferred degree of degeneracy between charginos and the LSP and study the effect this degree of degeneracy has on the prospects for direct detection of relic neutralinos in the next round of dark matter detection experiments. Lastly, we compare the fine tuning required to achieve a satisfactory relic density with the case of universal gaugino masses, as in minimal supergravity, and find it to be of a similar magnitude. The sensitivity of quantifiable measures of fine-tuning on such factors as the gluino mass and top and bottom masses is also examined.Comment: Uses RevTeX; 14 pages, 16 figure

Physics Implications of Flat Directions in Free Fermionic Superstring Models II: Renormalization Group Analysis

We continue the investigation of the physics implications of a class of flat directions for a prototype quasi-realistic free fermionic string model (CHL5), building upon the results of the previous paper in which the complete mass spectrum and effective trilinear couplings of the observable sector were calculated to all orders in the superpotential. We introduce soft supersymmetry breaking mass parameters into the model, and investigate the gauge symmetry breaking patterns and the renormalization group analysis for two representative flat directions, which leave an additional $U(1)'$ as well as the SM gauge group unbroken at the string scale. We study symmetry breaking patterns that lead to a phenomenologically acceptable $Z-Z'$ hierarchy, $M_{Z^{'}} \sim {\cal O}(1~{\rm TeV})$ and $10^{12}~{\rm GeV}$ for electroweak and intermediate scale $U(1)^{'}$ symmetry breaking, respectively, and the associated mass spectra after electroweak symmetry breaking. The fermion mass spectrum exhibits unrealistic features, including massless exotic fermions, but has an interesting $d$-quark hierarchy and associated CKM matrix in one case. There are (some) non-canonical effective $\mu$ terms, which lead to a non-minimal Higgs sector with more than two Higgs doublets involved in the symmetry breaking, and a rich structure of Higgs particles, charginos, and neutralinos, some of which, however, are massless or ultralight. In the electroweak scale cases the scale of supersymmetry breaking is set by the $Z^{'}$ mass, with the sparticle masses in the several TeV range.Comment: 38 pages, 5 figures, LaTex. Minor correction

Theory-Motivated Benchmark Models and Superpartners at the Tevatron

Recently published benchmark models have contained rather heavy superpartners. To test the robustness of this result, several benchmark models have been constructed based on theoretically well-motivated approaches, particularly string-based ones. These include variations on anomaly and gauge-mediated models, as well as gravity mediation. The resulting spectra often have light gauginos that are produced in significant quantities at the Tevatron collider, or will be at a 500 GeV linear collider. The signatures also provide interesting challenges for the LHC. In addition, these models usually account for electroweak symmetry breaking with relatively less fine-tuning than previous benchmark models.Comment: 44 pages, 4 figures; some typos corrected. Revisions reflect published versio

CP Violation in Supersymmetric U(1)' Models

The supersymmetric CP problem is studied within superstring-motivated extensions of the MSSM with an additional U(1)' gauge symmetry broken at the TeV scale. This class of models offers an attractive solution to the mu problem of the MSSM, in which U(1)' gauge invariance forbids the bare mu term, but an effective mu parameter is generated by the vacuum expectation value of a Standard Model singlet S which has superpotential coupling of the form SH_uH_d to the electroweak Higgs doublets. The effective mu parameter is thus dynamically determined as a function of the soft supersymmetry breaking parameters, and can be complex if the soft parameters have nontrivial CP-violating phases. We examine the phenomenological constraints on the reparameterization invariant phase combinations within this framework, and find that the supersymmetric CP problem can be greatly alleviated in models in which the phase of the SU(2) gaugino mass parameter is aligned with the soft trilinear scalar mass parameter associated with the SH_uH_d coupling. We also study how the phases filter into the Higgs sector, and find that while the Higgs sector conserves CP at the renormalizable level to all orders of perturbation theory, CP violation can enter at the nonrenormalizable level at one-loop order. In the majority of the parameter space, the lightest Higgs boson remains essentially CP even but the heavier Higgs bosons can exhibit large CP-violating mixings, similar to the CP-violating MSSM with large mu parameter.Comment: 29 pp, 3 figs, 2 table

Physics Implications of Flat Directions in Free Fermionic Superstring Models I: Mass Spectrum and Couplings

From the "top-down" approach we investigate physics implications of the class of D- and F- flat directions formed from non-Abelian singlets which are proven flat to all orders in the nonrenormalizable superpotential, for a prototype quasi-realistic free fermionic string model with the standard model gauge group and three families (CHL5). These flat directions have at least an additional U(1)' unbroken at the string scale. For each flat direction, the complete set of effective mass terms and effective trilinear superpotential terms in the observable sector are computed to all orders in the VEV's of the fields in the flat direction. The "string selection-rules" disallow a large number of couplings allowed by gauge invariance, resulting in a massless spectrum with a large number of exotics, in most cases excluded by experiment, thus signifying a generic flaw of these models. Nevertheless, the resulting trilinear couplings of the massless spectrum possess a number of interesting features which we analyse for two representative flat directions: for the fermion texture; baryon- and lepton-number violating couplings; R-parity breaking; non-canonical mu terms; and the possibility of electroweak and intermediate scale symmetry breaking scenarios for U(1)'. The gauge coupling predictions are obtained in the electroweak scale case. Fermion masses possess t-b and tau-mu universality, with the string scale Yukawa couplings g and $g/\sqrt{2}$, respectively. Fermion textures are present for certain flat directions, but only in the down-quark sector. Baryon- and lepton- number violating couplings can trigger proton-decay, $N-{\bar N}$ oscillations, leptoquark interactions and R-parity violation, leading to the absence of a stable LSP.Comment: 36 pages, 5 tables, 4 figures, RevTeX, minor change