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"Elegant" (compact) programs, "good" (fast) programs : The notion of "simplicity and elegance" appears informally in Knuth and precisely in Chaitin:

Chaitin prefaces his definition with: "I'll show you can't prove that a program is 'elegant'"—such a proof would solve the Journee Collection Ramsey Womens Ankle Boots Cheapest QVTfG
(ibid).

Algorithm versus function computable by an algorithm : For a given function multiple algorithms may exist. This is true, even without expanding the available instruction set available to the programmer. Rogers observes that "It is . . . important to distinguish between the notion of algorithm , i.e. procedure and the notion of function computable by algorithm , i.e. mapping yielded by procedure. The same function may have several different algorithms". [32]

Unfortunately there may be a tradeoff between goodness (speed) and elegance (compactness)—an elegant program may take more steps to complete a computation than one less elegant. An example that uses Euclid's algorithm appears below.

Computers (and computors), models of computation : A computer (or human "computor" [33] ) is a restricted type of machine, a "discrete deterministic mechanical device" [34] that blindly follows its instructions. adidas Originals NMD Cs1 GoreTex Trainers In White discount top quality marketable sale online buy cheap find great clearance choice real sale online k31niRMk
Melzak's and Lambek's primitive models [36] reduced this notion to four elements: (i) discrete, distinguishable locations , (ii) discrete, indistinguishable counters [37] (iii) an agent, and (iv) a list of instructions that are effective relative to the capability of the agent. [38]

Minsky describes a more congenial variation of Lambek's "abacus" model in his "Very Simple Bases for Journee Collection Finley Womens Ankle Boots wiki sale best sale free shipping supply best prices for sale Gt2OR
". [39] Minsky's machine proceeds sequentially through its five (or six, depending on how one counts) instructions, unless either a conditional IF–THEN GOTO or an unconditional GOTO changes program flow out of sequence. Besides HALT, Minsky's machine includes three assignment (replacement, substitution) Skechers Premium Seeing Double Womens Shoes get to buy cheap online pKvV91KmjF
operations: ZERO (e.g. the contents of location replaced by 0: L ← 0), SUCCESSOR (e.g. L ← L+1), and DECREMENT (e.g. L ← L − 1). [41] Rarely must a programmer write "code" with such a limited instruction set. But Minsky shows (as do Melzak and Lambek) that his machine is adidas NEO VL Court 20 Mens Sneakers 2014 newest cheap online fSC3lzUs
with only four general types of instructions: conditional GOTO, unconditional GOTO, assignment/replacement/substitution, and HALT. [42]

In terms of scope, note that there is a closely related, additional, important, discussion emerging about the melding of algorithms and robotics (for example, autonomous vehicles of various types, or drones) and questions about accountability and transparency, as well as fundamental assumptions, in these systems, particularly when they are intended to harm humans, or are forced by events to choose which humans to harm. I will leave such questions as out of scope; the issues here are very complex and raise many new considerations. My focus here is on systems that simply process data and produce informational outputs as opposed to animating robotic devices; though they may have real-world consequences, these consequences are not instantaneous, and perhaps not as dire.

The “Age of Algorithms”

Algorithms have been, of course, familiar to mathematicians for centuries, indeed millennia. Euclid devised an algorithm for factoring prime numbers in classical times (though he did not use the term); my understanding is that the term derives from medieval Arabic [ Tods Gommino City loafers cheap sale looking for footlocker finishline cheap price 3FQDz
]. It has gone in and out of usage over the centuries since. Algorithms were not grandiose things, but simply methods for solving specific problems.

In the twentieth century, predecessor disciplines growing out of mathematics towards computer science (such as the theory of computability) adopted the concept, both in very theoretical work (Turing, Gödel, , though to the best of my knowledge they did not use the term “algorithms,” speaking instead about questions like “halting problems” and “computability” that are in fact essential parts of what constitute algorithms) and in more applied bodies or work such as that of John von Neumann. The great computer scientist Donald Knuth was perhaps most central (though certainly not the first) in making both the concept and the actual term widely adopted in applied computer science in his magisterial work (Knuth, 1997); the first edition of the first volume of this work, , was published in 1968. The first chapter of this work contains a wonderful brief history and discussion of the definitions of algorithms and cannot be more highly recommended to interested readers. Again, in Knuth’s work, algorithms here were characterized as fairly modest things: well-specified computational procedures that could be proved to complete in a finite number of steps with a correct result [ 2 ].

During the second decade of the twenty-first century, legal scholars, public policy experts and regulators, and social scientists appropriated the term “algorithms” to mean something different, much broader and more amorphous [ 3 ]. The term became a shorthand for what previously social scientists sometimes had called “complex socio-technical systems” being implemented at a very broad level, most commonly by very large corporations or governments [ Zeferino python leather boots sale shop offer best prices for sale release dates discount hot sale outlet in China sOEgM0
]. Perhaps confusingly, it also is frequently used to cover a huge number of decision-making algorithms that are part of various consumer-oriented services: for example, various kinds of personalization and recommendation engines are now well established and increasingly ubiquitous in consumer-oriented news, social media, and shopping sites. More recently, we are seeing a plethora of computational language translation services, speech transcription, facial recognition and photo classification and tagging systems, and similar developments. Usually, these systems actually embed and orchestrate a large number of algorithms (as computer scientists and programmers think of them) that are constantly and asynchronously changing and evolving.

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Research Article
Switching from biosimilar (Basalin) to originator (Lantus) insulin glargine is effective in Chinese patients with diabetes mellitus: a retrospective chart review [version 1; referees: 3 approved, 1 approved with reservations]
Xia Hu, Lei Zhang, Yanhu Dong, Chao Dong, Jikang Jiang, Weiguo Gao
Xia Hu, Lei Zhang, [...] Yanhu Dong, Chao Dong, Jikang Jiang, Weiguo Gao
PUBLISHED 18 四月 2018
Xia Hu Roles: Conceptualization, Data Curation, Investigation, Project Administration, Writing – Original Draft Preparation, Writing – Review Editing
Lei Zhang Roles: Conceptualization, Formal Analysis, Investigation, Methodology, Writing – Original Draft Preparation, Writing – Review Editing
Yanhu Dong Roles: Conceptualization, Investigation, Methodology, Writing – Original Draft Preparation, Writing – Review Editing
Chao Dong Roles: Conceptualization, Data Curation, Formal Analysis, Methodology, Writing – Original Draft Preparation, Writing – Review Editing
Jikang Jiang Roles: Conceptualization, Investigation, Methodology, Writing – Original Draft Preparation, Writing – Review Editing
Weiguo Gao Roles: Conceptualization, Formal Analysis, Investigation, Methodology, Project Administration, Supervision, Writing – Original Draft Preparation, Writing – Review Editing
REFEREE STATUS

Abstract

This study investigated the effectiveness and safety of switching from Basalin® to Lantus® in Chinese patients with diabetes mellitus (DM). A retrospective chart review conducted using the electronic medical records of patients hospitalized at the Qingdao Endocrine and Diabetes Hospital from 2005 to 2016. All patients were diagnosed with DM and underwent switching of insulin from Basalin to Lantus during hospitalization. Data collected included fasting (FBG), pre- and post-prandial whole blood glucose, insulin dose, reasons for insulin switching and hypoglycemia. Four study time points were defined as: hospital admission, Basalin initiation, insulin switching (date of final dose of Basalin), and hospital discharge. Blood glucose measurements were imputed as the values recorded closest to the dates of these four time points for each patient. Data from 73 patients (70 patients with type 2 diabetes, 2 with type 1, and 1 undisclosed) were analyzed. At admission, mean glycated hemoglobin (HbA1c) and FBG were 8.9% (SD=1.75) and 9.98 (3.22) mmol/L, respectively. Between Basalin initiation and insulin switch, mean FBG decreased from 9.68 mmol/L to 8.03 mmol/L (p<0.0001), over a mean 10.8 (SD=6.85) days of Basalin treatment, and reduced further to 7.30 mmol/L at discharge (p=0.0116) following a mean 6.6 (7.36) days of Lantus. The final doses of Basalin and Lantus were similar (0.23 vs. 0.24 IU/kg/day; p=0.2409). Furthermore, reductions in pre- and post-prandial blood glucose were also observed between Basalin initiation, insulin switch and hospital discharge. The incidence of confirmed hypoglycemia was low during Basalin (2 [2.4%]) and Lantus (1 [1.2%]) treatment, with no cases of severe hypoglycemia. In this study population, switching from Basalin to Lantus was associated with further reductions in blood glucose, although the dose of insulin glargine did not increase. Further studies are required to verify these findings and determine the reason for this phenomenon.

Keywords

Insulin glargine, biosimilar, diabetes mellitus, Lantus, Basalin

Corresponding Author(s)
Weiguo Gao ( weiguo.gao@diabeteschina.com )
Grant information: The author(s) declared that no grants were involved in supporting this work.

Introduction

In China, insulin is more widely used to treat patients with type 2 diabetes mellitus (T2DM) compared with many Western countries. Chinese patients with T2DM are characterized by a relatively young age of diabetes onset, low bodyweight, and early β-cell dysfunction combined with insulin resistance. Furthermore, progressive deterioration of β-cell function is known to contribute to the increasing difficulty of achieving glycemic control experienced during the T2DM disease course. Therefore, interventions to preserve β-cells are recognized to be effective and, considering the early β-cell dysfunction which characterizes Chinese T2DM patients, can be especially effective in this population. However, challenges for implementing insulin treatment in China include lack of patient education, limitations of medical resources, inadequate health care systems making patient follow up difficult, and suboptimal blood glucose monitoring. Therefore, Chinese physicians often prefer to initiate intensified treatment regimens in an inpatient setting to allow close control of treatment, and monitoring of effectiveness and safety. Given this situation, early initiation of insulin treatment in an inpatient setting is often favored in China for the treatment of patients with T2DM. Several studies in Chinese patients with newly-diagnosed T2DM have shown that early intensive insulin treatment preserves β-cell function and leads to glycemic remission. Furthermore, a meta-analysis of previous studies showed that 46.3% of Chinese patients with T2DM who received intensive insulin treatment achieved glycemic remission after 12 months, without the use of anti-diabetic medication and relying solely on lifestyle modification to control blood glucose levels.

Basal insulin is recommended as a convenient way to initiate insulin treatment by most international treatment guidelines, and by the Chinese Diabetes Association. ( see the International Diabetes Federations Diabetes Atlas, 7 edition ) As reported by the large, observational ORBIT study, insulin glargine is the most popular basal insulin for the initiation of insulin treatment in Chinese patients with T2DM (71%), followed by detemir (13%) and neutral protamine Hagedorn (NPH)(16%) insulin. In China, there are two available versions of insulin glargine; the originator Lantus® (Sanofi), and the biosimilar Basalin® ( see Gan Lee Pharmaceuticals history page ), which has been commercially available since 2005 in China, Egypt, Pakistan, South East Asia, and countries in Latin America. Basalin was the first biosimilar of insulin glargine marketed in China, and has since become a commonly used treatment option for many Chinese physicians. However, while biosimilars are developed to be highly similar to originator therapies, due to the degree of natural variability inherent to biological drugs, which are produced using living organisms, and because of differences in manufacturing processes between products, they are not identical to the original therapy. Results from a previous head-to-head study of Basalin and Lantus in Chinese people with T2DM showed equivalent glycemic control and safety, and a further crossover study in Chinese people with T2DM using a continuous glucose monitoring system (CGMS) reported non-inferiority of Basalin to Lantus for mean blood glucose, blood glucose fluctuations and rates of hypoglycemia. However, other than these two previous reports, there are no further confirmatory studies in real-world clinical practice. In addition, a local-language case report described improved blood glucose control and reduced insulin dose in three Chinese patients with T2DM who switched from Basalin to Lantus due to suboptimal glycemic control. Given this situation, it is important to further verify the findings of this case report in a larger population of patients who switched from Basalin to Lantus in a real-life clinical practice setting. We therefore hypothesized that patients with diabetes who switch from Basalin to Lantus in a real-world setting may achieve improved control of blood glucose with a similar safety profile.

This was a retrospective chart review conducted based on the electronic medical records (EMRs) of patients hospitalized at the Qingdao Endocrine and Diabetes Hospital from 2005 to 2016. Qingdao Endocrine and Diabetes Hospital is a public, non-profit, tertiary hospital that was established in 2002 and is located in Qingdao city, one of the biggest cities on the east coast of China. The Hospital is the only specialist diabetes hospital, not only in Qingdao, but also throughout the region, with a catchment area of approximately 100 kilometers, which covers 7.2 million people. The majority of the patients treated in the Hospital are Han Chinese residing in Qingdao city and the surrounding regions. Less than 1% of patients are national ethnic minorities or of foreign origin. In general, patients are hospitalized due to suspected acute diabetic complications including ketosis, ketoacidosis, diabetic hyperosmolality, uncontrolled hyperglycemia and at least one chronic complication, or significant worsening of chronic complications of diabetes (including rental hemorrhage, significant elevated albuminuria and/or serum creatinine, acute myocardial infarction, etc.).

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