Tetris is Hard, Even to Approximate

In the popular computer game of Tetris, the player is given a sequence of tetromino pieces and must pack them into a rectangular gameboard initially occupied by a given configuration of filled squares; any completely filled row of the gameboard is cleared and all pieces above it drop by one row. We prove that in the offline version of Tetris, it is NP-complete to maximize the number of cleared rows, maximize the number of tetrises (quadruples of rows simultaneously filled and cleared), minimize the maximum height of an occupied square, or maximize the number of pieces placed before the game ends. We furthermore show the extreme inapproximability of the first and last of these objectives to within a factor of p^(1-epsilon), when given a sequence of p pieces, and the inapproximability of the third objective to within a factor of (2 - epsilon), for any epsilon>0. Our results hold under several variations on the rules of Tetris, including different models of rotation, limitations on player agility, and restricted piece sets.Comment: 56 pages, 11 figure

Simulation of Classical Thermal States on a Quantum Computer: A Transfer Matrix Approach

We present a hybrid quantum-classical algorithm to simulate thermal states of a classical Hamiltonians on a quantum computer. Our scheme employs a sequence of locally controlled rotations, building up the desired state by adding qubits one at a time. We identify a class of classical models for which our method is efficient and avoids potential exponential overheads encountered by Grover-like or quantum Metropolis schemes. Our algorithm also gives an exponential advantage for 2D Ising models with magnetic field on a square lattice, compared with the previously known Zalka's algorithm.Comment: 5 pages, 3 figures; (new in version 2: added new figure, title changed, rearranged paragraphs

Pharmacological Advances in Opioid Therapy: A Review of the Role of Oliceridine in Pain Management

Problems with the treatment of acute pain may arise when a patient is opioid-tolerant, such as those on chronic therapy with opioids or opiate replacement therapy, those who misuse opioids, and those who are in recovery. While some of the adverse effects of opioid medications are well known, it is also important to recognize the roles of tolerance and hyperalgesia. Oliceridine can target and modulate a novel μ-receptor pathway. The G protein-biased agonism of oliceridine allows for effective re-sensitization and desensitization of the mu-opioid receptor, which decreases the formation of opioid tolerance in patients. Oliceridine has been demonstrated to be an effective and relatively safe intravenous analgesic for the treatment of postoperative pain and is generally well tolerated with a favorable side effect profile when compared to morphine. As the prevalence of pain increases, it is becoming increasingly important to find safe and effective analgesics

Antipsychotic Polypharmacy-Related Cardiovascular Morbidity and Mortality: A Comprehensive Review

Schizophrenia is a psychotic disorder that exists at the more extreme end of a spectrum of diseases, and significantly affects daily functioning. Cardiovascular adverse effects of antipsychotic medications are well known, and include changes in blood pressure and arrhythmias. Sudden cardiac death is the leading cause of death worldwide, and antipsychotic medications are associated with numerous cardiac side effects. A possible link exists between antipsychotic medications and sudden cardiac death. Common prescribing patterns that may influence cardiovascular events include the use of multiple antipsychotics and/or additional drugs commonly prescribed to patients on antipsychotics. The results of this review reflect an association between antipsychotic drugs and increased risk of ventricular arrhythmias and sudden cardiac death by iatrogenic prolongation of the QTc interval. QTc prolongation and sudden cardiac death exist in patients taking antipsychotic monotherapy. The risk increases for the concomitant use of specific drugs that prolong the QTc interval, such as opioids, antibiotics, and illicit drugs. However, evidence suggests that QTc intervals may not adequately predict sudden cardiac death. In considering the findings of this narrative review, we conclude that it is unclear whether there is a precise association between antipsychotic polypharmacy and sudden cardiac death with QTc interval changes. The present narrative review warrants further research on this important potential association

Combination Olanzapine and Samidorphan for the Management of Schizophrenia and Bipolar 1 Disorder in Adults: A Narrative Review

Schizophrenia is a debilitating psychotic disorder characterized by positive symptoms such as delusions, hallucinations, and disorganized thoughts, and negative symptoms like lack of effect or motivation. Bipolar 1 disorder (B1D) is a psychiatric illness characterized by recurrent manic episodes in alternation with depressive episodes and interspersed periods of euthymia, ultimately resulting in psychological distress and impairment of daily functioning. Effective treatments are needed for both schizophrenia and B1D to reach the treatment goals of reducing the debilitating symptomology, improving social functioning and quality of life, and increasing the chances of recovery and more favorable long-term outcomes. To date, olanzapine is one of the most efficacious atypical antipsychotics (AAPs) for the treatment of both schizophrenia and B1D and is associated with fewer extrapyramidal effects compared to other treatments. However, compared to other AAPs, olanzapine is associated with a greater chance of metabolic syndrome, limiting its clinical use and affecting treatment compliance. Samidorphan mitigates the weight gain side effects of olanzapine by antagonizing μ-, κ-, and δ-opioid receptors. The use of combination drugs to treat psychiatric conditions is an emerging field with the goal of increasing therapeutic efficacy and decreasing undesirable side effects. Clinical trials have demonstrated combination on olanzapine and samidorphan (OLZ/SAM) treatment resulted in significantly less weight gain than olanzapine monotherapy. Clinical trial patients reported improvements in symptoms of psychosis, reduced weight gain, and overall satisfaction with their treatment. OLZ/SAM has been as shown to be a safe and effective pharmaceutical option for the clinical management of schizophrenia and B1D

Chronic pain treatment strategies in Parkinson’s disease

Neurological disorders, including Parkinson’s disease (PD), have increased in prevalence and are expected to further increase in the coming decades. In this regard, PD affects around 3% of the population by age 65 and up to 5% of people over the age of 85. PD is a widely described, physically and mentally disabling neurodegenerative disorder. One symptom often poorly recognized and under-treated by health care providers despite being reported as the most common non-motor symptom is the finding of chronic pain. Compared to the general population of similar age, PD patients suffer from a significantly higher level and prevalence of pain. The most common form of pain reported by Parkinson’s patients is of musculoskeletal origin. One of the most used combination drugs for PD is Levodopa-Carbidopa, a dopamine precursor that is converted to dopamine by the action of a naturally occurring enzyme called DOPA decarboxylase. Pramipexole, a D2 dopamine agonist, and apomorphine, a dopamine agonist, and Rotigotine, a dopamine receptor agonist, have showed efficacy on PD-associated pain. Other treatments that have shown efficacy in treating pain of diverse etiologies are acetaminophen, Nonsteroidal anti-inflammatory drugs (NSAIDs), and cyclooxygenase-2 (COX-2) inhibitors. Opioids and opioid-like medications such as oxycodone, morphine, tramadol, and codeine are also commonly employed in treatment of chronic pain in PD. Other opioid related medications such as Tapentadol, a central-acting oral analgesic with combined opioid and noradrenergic properties, and Targinact, a combination of the opioid agonist oxycodone and the opioid antagonist naloxone have shown improvement in pain. Anticonvulsants such as gabapentin, pregabalin, lamotrigine, carbamazepine and tricyclic antidepressants (TCAs) can be trialed when attempting to manage chronic pain in PD. The selective serotonin and noradrenaline reuptake inhibitors (SNRIs) also possess pain relieving and antidepressant properties, but carry less of the risk of anticholinergic side effects seen in TCAs. Deep brain stimulation (DBS) of the subthalamic nucleus (STN) has been shown in multiple studies to be effective against various types of PD associated pain symptoms. Massage therapy (MT) is one of the most common forms of complementary and alternative medicine. Studies have shown that pressure applied during MT may stimulate vagal activity, promoting reduced anxiety and pain, as well as increasing levels of serotonin. In a survey study of PD patients, rehabilitative therapy and physical therapy were rated as the most effective for pain reduction, though with only temporary relief but these studies were uncontrolled. Yoga has been studied for patients with a wide array of neurological disorders. In summary, PD pathology is thought to have a modulating effect on pain sensation, which could amplify pain. This could help explain a portion of the higher incidence of chronic pain felt by PD patients. A treatment plan can be devised that may include dopaminergic agents, acetaminophen, NSAIDs, opioids, antidepressants, physical therapies, DBS and other options discussed in this review. A thorough assessment of patient history and physical examination should be made in patients with PD so chronic pain may be managed effectively

Chronic pain treatment strategies in Parkinson’s disease

Neurological disorders, including Parkinson’s disease (PD), have increased in prevalence and are expected to further increase in the coming decades. In this regard, PD affects around 3% of the population by age 65 and up to 5% of people over the age of 85. PD is a widely described, physically and mentally disabling neurodegenerative disorder. One symptom often poorly recognized and under-treated by health care providers despite being reported as the most common non-motor symptom is the finding of chronic pain. Compared to the general population of similar age, PD patients suffer from a significantly higher level and prevalence of pain. The most common form of pain reported by Parkinson’s patients is of musculoskeletal origin. One of the most used combination drugs for PD is Levodopa-Carbidopa, a dopamine precursor that is converted to dopamine by the action of a naturally occurring enzyme called DOPA decarboxylase. Pramipexole, a D2 dopamine agonist, and apomorphine, a dopamine agonist, and Rotigotine, a dopamine receptor agonist, have showed efficacy on PD-associated pain. Other treatments that have shown efficacy in treating pain of diverse etiologies are acetaminophen, Nonsteroidal anti-inflammatory drugs (NSAIDs), and cyclooxygenase-2 (COX-2) inhibitors. Opioids and opioid-like medications such as oxycodone, morphine, tramadol, and codeine are also commonly employed in treatment of chronic pain in PD. Other opioid related medications such as Tapentadol, a central-acting oral analgesic with combined opioid and noradrenergic properties, and Targinact, a combination of the opioid agonist oxycodone and the opioid antagonist naloxone have shown improvement in pain. Anticonvulsants such as gabapentin, pregabalin, lamotrigine, carbamazepine and tricyclic antidepressants (TCAs) can be trialed when attempting to manage chronic pain in PD. The selective serotonin and noradrenaline reuptake inhibitors (SNRIs) also possess pain relieving and antidepressant properties, but carry less of the risk of anticholinergic side effects seen in TCAs. Deep brain stimulation (DBS) of the subthalamic nucleus (STN) has been shown in multiple studies to be effective against various types of PD associated pain symptoms. Massage therapy (MT) is one of the most common forms of complementary and alternative medicine. Studies have shown that pressure applied during MT may stimulate vagal activity, promoting reduced anxiety and pain, as well as increasing levels of serotonin. In a survey study of PD patients, rehabilitative therapy and physical therapy were rated as the most effective for pain reduction, though with only temporary relief but these studies were uncontrolled. Yoga has been studied for patients with a wide array of neurological disorders. In summary, PD pathology is thought to have a modulating effect on pain sensation, which could amplify pain. This could help explain a portion of the higher incidence of chronic pain felt by PD patients. A treatment plan can be devised that may include dopaminergic agents, acetaminophen, NSAIDs, opioids, antidepressants, physical therapies, DBS and other options discussed in this review. A thorough assessment of patient history and physical examination should be made in patients with PD so chronic pain may be managed effectively

Mixing Times in Quantum Walks on Two-Dimensional Grids

Mixing properties of discrete-time quantum walks on two-dimensional grids with torus-like boundary conditions are analyzed, focusing on their connection to the complexity of the corresponding abstract search algorithm. In particular, an exact expression for the stationary distribution of the coherent walk over odd-sided lattices is obtained after solving the eigenproblem for the evolution operator for this particular graph. The limiting distribution and mixing time of a quantum walk with a coin operator modified as in the abstract search algorithm are obtained numerically. On the basis of these results, the relation between the mixing time of the modified walk and the running time of the corresponding abstract search algorithm is discussed.Comment: 11 page

Electron spin relaxation of N@C60 in CS2

We examine the temperature dependence of the relaxation times of the molecules N@C60 and N@C70 (which comprise atomic nitrogen trapped within a carbon cage) in liquid CS2 solution. The results are inconsistent with the fluctuating zero field splitting (ZFS) mechanism, which is commonly invoked to explain electron spin relaxation for S > 1/2 spins in liquid solution, and is the mechanism postulated in the literature for these systems. Instead, we find a clear Arrhenius temperature dependence for N@C60, indicating the spin relaxation is driven primarily by an Orbach process. For the asymmetric N@C70 molecule, which has a permanent non-zero ZFS, we resolve an additional relaxation mechanism caused by the rapid reorientation of its ZFS. We also report the longest coherence time (T2) ever observed for a molecular electron spin, being 0.25 ms at 170K.Comment: 6 pages, 6 figures V2: Updated to published versio

Liquid-like behaviour of gold nanowire bridges

A combination of Focused Ion Beam (FIB) and Reactive Ion Etch (RIE) was used to fabricate free standing gold nanowire bridges with radii of 30 nm and below. These were subjected to point loading to failure at their mid-points using an Atomic Force Microscope (AFM), providing strength and deformation data. The results demonstrate a dimensionally dependent transition from conventional solid metallic properties to liquid-like behaviour including the unexpected reformation of a fractured bridge. The work reveals mechanical and materials properties of nanowires which could have significant impact on nanofabrication processes and nanotechnology devices such as Nano Electro Mechanical Systems (NEMS)